Chemotherapeutic Properties of Boerhaavia Diffusa and Black Caraway Oil on DMBA-Induced Carcinogenesis and Hypercholesterolemia in Animals

Supervision By
Dr. R.P. Thapliyal

Ph.D. Thesis Presentation By Subodh Kumar Chauhan

Department of Zoology & Biotechnology
Faculty of Life Science

H.N.B. Garhwal Central University, Srinagar (Garhwal)

Boerhaavia diffusa is a medicinal plant widely used in the Ayurvedic medicine. Ayurveda is an ancient traditional medical system of health care of the Veda civilization, flourishing in India many thousand years ago. The term “AYURVEDA” means “Knowledge or Science of Life” (From “Ayus” meaning “life” and “Veda” meaning “acquaintance”, “science”) in Sanskrit. In fact, Ayurveda focuses on the physical, spiritual and mental aspects of an individual. The plant was named in honor of Hermann Boerhaave, a famous Dutch physician of the 18th century (Chopra, 1969). B. diffusa (Spreading Hogweed in English) belonging to the family of the Nyctaginaceae, is mainly diffused perennial herbaceous creeping weed of India (known also under its traditional name as Punarnava). B. diffusa is up to 1 m long or more, having spreading branches. The stem is prostrate, woody or succulent, cylindrical, often purplish, hairy, and thickened at its nodes. The last two decades witnessed an enormous research rush to reveal the pharmacological actions of an annual spicy delicate and beautiful herb known by the Latin name Nigella sativa Linnaeus (Black Caraway Oil) variety hispidula (brachyloba) that belongs to the botanical family Ranunculaceae. The plant is an erect profusely branched herb that can attain heights of 40 and up to 70cm.

Cancer is the second most common cause of death after cardiovascular diseases (CVD) in most developed and in many developing countries, including India. In this country, every year around seven million new cases of cancer are being detected. The global burden of cancer doubled during the last 30 years of the last century. In 2008, it is estimated that there were over 12 million new cases of cancer diagnosed, 7 million deaths from cancer and 25 million persons alive with cancer within five years of diagnosis. The continued growth and ageing of the world’s population has immediate consequences on the cancer burden. By 2030, it is estimated that there will be over 26 million incident cases of cancer annually.(IARC-W.H.O. Report 2008). Lung, stomach, liver, colon and breast cancer cause the most cancer deaths each year. About 30% of cancer deaths can be prevented. The change may be started by external agents and inherited genetic factors. About 72% of all cancer deaths in 2007 occurred in low- and middle-income countries. Deaths from cancer worldwide are projected to continue rising, with an estimated 12 million deaths in 2030, (WHO-2010).

The 20th century saw unparalleled increases in life expectancy and a major shift in the causes of illness and death throughout the world. A century ago, cardiovascular disease (CVD) accounted for fewer than 10% of all deaths; today, it accounts for approximately 30% worldwide (Gaziano, T.A., 2005; Yusuf S. et al., 2001). The increase in CVD, through a proliferation of risk factors that are heavily influenced by lifestyle choices, is the new challenge for many developing countries. Cardiovascular diseases accounted for 16.7 million or 29.2 % of the total global deaths in 2002, according to the World health report 2003, around 80 % of deaths due to CVD took place in low- and middle-income countries. By 2010, The contribution of developing countries to the global burden of CVD, in terms of disabilityadjusted life-years lost, was 2.8 times higher than that in developed countries (Reddy and Yusuf, 1998). By 2020, about 42 % of the total deaths in India are projected to be due to cardiovascular causes (Murray and Lopez, 1996). During the period 2000-2030, about 35 % of all deaths due to CVD in India are projected to occur in the age group of 35-64 years (Leeder et al., 2004).

resulting in a several fold increase in its activity and cholesterol formation. the rate controlling enzyme in the cholesterol biosynthetic pathway. Increased HMG-CoA reductase activity in tumour cells is associated with unrestricted supply of farnesyl pyrophosphates.  We investigated the effect of aqueous ethanolic extract of B. In tumour cells. which also results in hypercholesterolemia and subsequently CVD. Several lines of research have established that both CVD and most prominent ras growth protein-induced cancers are coupled and controlled by a common mechanism involving the up regulation of HMG-CoA reductase. the feed-back mechanism at the level of HMG-CoA reductase is flopped. diffusa and Black Caraway Oil on DMBA-Induced carcinogenesis and hypercholesterolemia in animals which was not studied earlier. . for rapidly proliferating tumours.

. O. 1971). 2008). 2003)... 1976). Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: an experimental model. antihepatotoxi (Mishra. E. M. antileprotic. antihelmintic. 1993). et al.. (Kanter.. antifibrionolitic and anti-inflammatory activities (Hiruma-Lima. antinematodal (Vijayalakshmi et al. 2004).The first pharmacological studies have demonstrated that the root of punarnava exhibits a wide range of properties: anti-inflammatory (Bhalla et al. J.. laxative (Chopra et al. (Bayrak. anti-urethritis (Nadkarni. 2001).. 1997). (Mansour.. 1968.... M. 1979). antiscabby and antistress activites. 1956). Protective effect of Nigella sativa seed against carbon tetrachloride-induced liver damage. et al. 2000). 2003). 2002). Effect of volatile oil constituents of Nigella sativa on carbon tetrachloride-induced hepatotoxicity in mice: evidence for antioxidant effect of thymoquinone. (Al-Ghamdi. 2008). The antioxidative and antihistaminic effect of Nigella sativa and its major constituent.. 2006). H. 2006).. antidiabetic activity (Pari et al. Effect of black cumin (Nigella sativa) on heart rate. 1989). The role of black seed in the proliferation and biochemical marker levels of Hep-2 cells. M. antibacterial (Olukoya et al.. Kanter. Effect of Nigella sativa on oxidative stress and beta-cell damage in streptozotocin-induced diabetic rats. Nigella sativa protect against ischaemia reperfusion injury rat kidney. Chandan et al.. febrifuge.. 2004). 1979). some hematological values and pancreatic beta-cell damage in cadmium-treated rats. anticonvulsant (Adesina. 1974). 1991. et al. thymoquinone on ethanol-induced gastric mucosal damage. Rawat et al. M. diuretic (Gaitonde et al.S. et al. et al. (Uz. et al.T. (Demir.A. 1980. antifibrinolytic (Jain and Khanna. immunosuppressive activity (Mehrotra et al. (Hansen. et al.

diffusa (Bd) and Black Caraway Oil (BCO). small dense (sd)-LDL-C and large buoyant (lb)-LDL-C in hyperlipidemic rats. Cardiovascular diseases (CVD) are more killer then Cancer in the world. creates a need to develop a simple and cost-effective methodology for the isolation and extraction of ethanolic roots of B. which is known to induce both carcinogenesis and hypercholesterolemia/CVD. VLDL-C. The proposed study designed to investigate both hypolipidemic and cancer chemotherapeutic properties of Boerhaavia Diffusa roots extracts and Black caraway Oil. diffusa (Bd) and Black Caraway Oil (BCO) extracts in preventing the increase in plasma triglycerides (TG). diffusa (Bd) and Black Caraway Oil (BCO) in the suppression of experimental carcinogenesis in rat liver and their impact on different marker enzymes. 3. total cholesterol (TC). Will be investigated carcinogen 7. Phytochemical Screening of B. To estimate the effect of ethanolic extract of B. 12-dimethylbenz [α] anthracene (DMBA). diffusa (Bd) and Black Caraway Oil (BCO) using HPLC. So. . To correlate the efficacy of B. 2. was used. 1. LDLC.

In rats with DMBA induced carcinogenesis coupled with hypercholesterolemia. both hypercholesterolemia and carcinogenesis mediate a sustained free radical load (Antioxidant power). . kidney and pancreas. 5. which could enhance lipid / lipoprotein peroxidation. Thus. anticholesterol effects on plasma and lipoprotein lipids and HMG-CoA reductase activity will also be investigated.and post-initiation and progression stages will also be examined histological in liver.4. in addition of Boerhaavia Diffusa and Black caraway Oil mediated anticancer impacts. diffusa (Bd) and Black Caraway Oil (BCO) in the suppression of carcinogeninduced cancer at pre. The role of B.

weighing about 150-180 g were purchased from Indian Veterinary Research Institute. Diet The rats were given pelleted rat chow and tap water ad libitum. . Animal experimentation protocols conform to the Institutional Animal Ethics committee’s guidelines. Bareilly. 1977). were maintained to animal house under standard normal condition having natural photoperiod (12 hours light/dark cycle) at temperature 25±10C and 50-60% humidity.w.orally) were solubilised in methanol. The hairs on dorsal skin of the animals in the interscapular area was shaved 3 days before the commencement of the experiment and only those animals in the resting phase of the hair cycle were taken for the study. Rat chow was administered as through orally. The rats were sacrificed at sixth hour of dark cycle at the peak of diurnal rhythm of HMG-CoA reductase (Edwards et al. Both Bd (1mg/ 1ml methanol stock) and BCO (2ml/Kg b. Bd and BCO suspension was also administrated through orally in two equal doses of 2 ml/Kg b.. Experimental rats from respective groups were administrated with Boerhaavia diffusa (Bd) and Black Caraway Oil (BCO). India. because resting hair retains carcinogens for a longer period.Animals White male albino rats.w.orally.

through orally and were feed rat chow for 16 weeks. 5ml/Kg b. Group IV .     Studies in rats For investigating the hypercholesterolemia. Group II . Group III . rats were divided in the following groups as described below: Group I . diffusa (Bd) and Black Caraway Oil (BCO).w.ip through intraperitoneal injection and were feed rat chow for 16 weeks.w.w.9% NaCl. Animals were infected in three weeks.Infected Black Caraway Oil Treated (I-BCOT) DMBA induced fifteen rats in this group were given a topical application of Black Caraway Oil two equal doses (morning and evening) of 2ml/Kg b.Normal Control (N-C) Fifteen rats were given a single dose of 0. diffusa extract dissolve in 1mg/1ml methanol and two equal doses (morning and evening) of 2 ml/Kg b. carcinogens and antioxidant effect of B.Infected Control (I-C) Fifteen rats in this group were given a single dose of 65 mg/Kg body weight of DMBA in Acetone though intraperitoneal injection and were feed rat chow for 16 weeks. through orally and were feed rat chow for 16 weeks. .Infected B. Diffusa Treated (I-BdT) DMBA induced fifteen rats in this group were given a topical application of B.

The final extract was filtered and the remaining alcohol was allowed to evaporate. Painuly at the Botany Department of HNBGU and the specimen was preserved in the herbarium voucher no.L.Isolation and Aqueous ethanolic Extraction of Boerhaavia diffusa roots (Bd) The fresh roots of Boerhaavia diffusa linn. (1978). shad-dried avoiding sun drying due to the signature modification of the biochemical's. The plant material roots were washed. C. using an isocratic mobile phase of water: methanol: 2-propanol (50: 45: 5% v/v) at a flow rate of 1ml/min. Extraction of the constituents from Bd and BCO were carried out using C18 PrepSep mini columns followed by quantification of the recovered constituvents by HPLC on a reversed-phase muBondapack C18 analytical column. GUH20434. and finally sieved. (Punarnava) were collected from the foothills of Dehradun (Uttarakhand) and its adjoining area and identified by Dr. detection was 254nm. therein under the influence of UV radiation (Sun-rays) pulverized. . which used as herbal medicine. HPLC of extract of B.F. R. 100 gm roots were then subjected to soxhlet extraction using 70% hydro-alcoholic solvent (70% ethanol: 30% distilled water). Black Caraway Oil parched market in Dehradun. diffusa (Bd) and Black Caraway Oil (BCO) The technical details have been described by Simpson.

Preparation of liver. lung and kidney were cut into pieces. a portion of each homogenate from liver. lung and kidney homogenate and post-mitochondrial supernatant At the end of the experiment.000 rpm for 10 min at 40C. lung and kidney homogenates were centrifuged at12. The blood from each rat in a given group was collected in heparinised tubes. overnight fasted rats in each group were anaesthetized and blood drawn from cardiac puncture.1 M sodium phosphate buffer. After washing with saline. Plasma was separated from blood by centrifugation at 2. mixed and 10 g of wet tissue was homogenized with 90 ml of chilled 0. 000 rpm for 20 min at 40C. liver. Collection of different organs In addition to the blood. Portion of organs was immediately fixed in 10% neutral formalin for histological studies. lung and kidney from each rat were promptly excised and chilled in ice cold saline. The volume of each homogenate was recorded and centrifuged at 1. liver. pH 7. liver.Analytical Procedures Collection of blood and packed erythrocytes At the end of the experiment treatment. Packed erythrocytes hemolysate was prepared as described by Lakshmi and Rajagopal (1998). After centrifugation.4. mixed gently by inversion 2-3 times and incubated at 40C for 2-3 h. lung and kidney thus obtained was aliquoted and stored at –200C. kidney and pancrease from male rats were excised that kept into ice cold saline. . containing 1. The post-mitochondrial supernatant thus obtained was aliquoted and stored at –200C for future use. lung and kidney were blotted and weighed.500 rpm for 30 min. aliquoted and stored at 40C or frozen at –200C for use in other experiments. The remaining portions of the liver. Each liver.17 % KCl in a waring blender.

The intensity of the color produced after incubation is directly proportional to the concentration of the triglycerides in the plasma samples when measured at 500 nm in a Beckman DU 640 spectrophotometer. 1969). linear. Determination of plasma triglycerides Triglycerides were determined by using enzymatic kit. diffusa and BCO The procedure of Mellors and Tappel (1966) as modified by Khanduja and Bhardwaj (2003) was used for determining the free radical scavenging activity of B. pH 7. The samples were mixed thoroughly and the absorbance was recorded in dark at 517 nm (27  20C) at 1 min time interval up to 10 min against absolute ethanol. VLDL. end point reaction (Trinder.Determination of free radical scavenging activity (antioxidant capacity) of B. Triglycerides in plasma samples were calculated by using a triolein standard. The method uses a modified Trinder color reaction to produce a fast. The reaction was started by the addition of ethanolic solution of B. diffusa and Black Caraway Oil. 2diphenyl-1-picryl hydrazyl (DPPH). The assay was carried out in a medium containing 40 mM tris buffer.4 and 125 M ethanolic solution of 2. GST. GPx) All parameter were estimated as described by slandered protocol. Catalase. diffusa and Black Caraway Oil (25-200 M) in a total volume of 2 ml. XO. HMG-CoA. . Lb-LDL. Determination of plasma free fatty acid Free fatty acid in plasma was estimated as described by Duncombe (1963). Sd-LDL. (1957) was used for extracting free fatty acid from plasma lipids. HDL. SOD. The procedure of Folch et al. Determination of all other parameter (LDL.

diffusa was continued into dry solid by rotary vacuum evaporator. diffusa (Bd) shows Boeravinone A1. HPLC extracts of B. diffusa was 7. C2.. which is marked as a medicine After both 1mg/1ml dilution in the methanol the extract was two equal doses of 2ml/Kg b. diffusa (Bd) and Black Caraway Oil (BCO) The aqueous extract of B. Whereas Black Caraway oil extracts from black cumin or Nigella sativa L. B1. al. dithymoquinone (DTQ).w. The powder obtained was stored at 40C till further use.78%.A. et. 1999). E. Pharmacological active constituents of the Black Caraway Oil (BCO) as found as thymoquinone (TQ). . Hypoxanthine.orally. F. The yield of B. seeds was obtained from the local market (100% pure).  Extraction of B. diffusa (Bd) and Black Caraway Oil (BCO) The fraction was purified by HPLC have eleven peaks of B. Punarnavoside and Urosolic acid as the major phytoconstituents and 4 main peaks found in Black Caraway Oil (BCO) in HPLC. D. thymohydroquinone (THQ) and thymol (THY) (Ghosheh. O.

diffusa (Bd). As shown in Fig. the half quenching concentrations (IC50) were as follows: B. which reflects the antioxidative properties of these compounds. 2. 38. Black Caraway Oil (BCO). These findings indicate that as compared to B.11 µM.2-diphenyl. diffusa (Bd) 89% was found more efficient then Black Caraway Oil (BCO) 76% respectively. diffusa (Bd) and Black Caraway Oil (BCO) Antiradical activity or hydrogen donating ability of B.2. diffusa shows more free radical scavenging property then Black Caraway Oil.1-picrylhydrazyl). 44.42 µM.  . Antioxidative Activities of B. B. diffusa (Bd) and Black Caraway Oil (BCO) was measured by using DPPH (2.

The average error in the data points in these assay were mean ± less than 3 %. The average absolute absorbance value of 100 % DPPH was 0. 2-diphenyl.00786 ± 0. The antioxidant activities of the above compounds at the indicated concentrations were carried out as described in methods. 2. which gives strong absorption maxima at 517nm. 1-picrylhydrazyl (DPPH).2. .Fig. Free radical scavenging activities of B. Values represent the mean of triplicate determinations. diffusa (Bd) and Black Caraway Oil (BCO). The assay is based on the reduction of 2.00029.

TABLE 1 IMPACT OF B.03%)a 13.011* (+17.016* (+22.960. normal control. I-C.440. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON HEMOGLOBIN IN DMBA-INDUCED RATS AFTER TREATMENT Hemoglobin Group N-C (g/dl) 14.001. Infected control.w. I-BdT. Significantly different from N-C at ap<0.280. through orally in two equal doses of 2ml/Kg b.orally and I-BCOT. .orally for 16 weeks.001. Significantly different from I-C at ap<0.69%)a *Values are mean ± SD from pooled blood or plasma of 15 rats in each group.24%)a I-C I-BdT I-BCOT 13.012* (-20. N-C. given through orally in two equal doses of 2ml/Kg b.420.264* 11.w.

05.86 (+74.46 154.310.w.48 %)a 102.12* (-4. I-BdT.w.71 %)b 54.92 %)a N-C I-C 390.150.001 and bp<0.3 %)a I-BdT I-BCOT *Values are mean (mg/dl) ± SD from pooled plasma of 15 rats in each group.38 %)a 66. .150. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON PLASMA TOTAL LIPID. I-C.662.612.412 151.291 (-9.79 %)a 483.211.43 (+111. TRIGLYCERIDES.221.orally for 16 weeks. through orally in two equal doses of 2ml/Kg b.56* (-5.78 %)a 137.46 %)a 110.622.TABLE 2 IMPACT OF B.212 (-11.17 114.683.76 (-33.05%)b 134.290. Significantly different from N-C at ap < 0. Significantly different from I-C at ap<0.32 %)b 486.23* (+30. normal control.362.311.88 (-28.221.orally and I-BCOT.681. given through orally in two equal doses of 2ml/Kg b.40* 510.191. N-C.33 %)a Total cholesterol 88.86 (-45.20 %)a 62.241. FREE FATTY ACID AND TOTAL CHOLESTEROL IN DMBA-INDUCED RATS AFTER TREATMENT Group Total lipid Triglycerides Free fatty acid 134. Infected control.512 (+12.001.92 (-42.

HDL-C.012 (-27.52 (-41. LDL-C.07 %)a 18.97 %)a LDL-C 54.165* (-38.88 *Values are mean (mg/dl) ± SD from pooled plasma of 15 rats in each group.040. N-C. I-BdT.orally for 16 weeks.89%)a 14.TABLE 3 IMPACT OF B.010.83 %)a 75.190. Infected control.34 %)a 79.072 (+34.192 (-47.880.68 %)a I-BdT 13.03 %)c 136.87 %)a 31. Significantly different from I-C at ap<0. through orally in two equal doses of 2ml/Kg b.C 68.74 %)a 17.043 (-4.260.214* (-38.w. Significantly different from N-C at ap<0.02.001 and cp<0.060.C 13.160.043 (-13.120.w.960. I-C.orally and I-BCOT. .93 %)a 5.071 (+42.022 (+175.643.910.010. given through orally in two equal doses of 2ml/Kg b.88 %)a 26.302 (-43.960.131 HDL.012 HDL3. HDL2-C AND HDL3-C SUBFRACTIONS AND NON-HDL-C IN DMBA-INDUCED RATS AFTER 16 WEEKS OF TREATMENT Parameters VLDL.014 (+ 117. normal control.C 20.C 7.440.080.120.176 (+49.89 %)a † Non-HDL.612.001.960. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON PLASMA VLDL-C.642.C N-C 11.17 %)a 11.960.89 (+99.73 %)a 111.303.15 %)a 57.242* (+94.75 %)a 18.11 (-44.220.265 (+105.420.48 %)a 62.78 %)a I-BCOT 13.320.054* I-C 21.106 (+71.042 13.071 HDL2.

w.462 (-45.302* (-43.18 %)a 41. given through orally in two equal doses of 2ml/Kg b.80 %)a 48.720.58 %)a 82.12 (+20.046 I-C 111.84 %)a 129.580.83 126.TABLE 4 IMPACT OF B. bp<0.420.51 %)a 69.424 (+20.600.17 %)a 32.95 %)a 82.060.129 (+54.835 (-26.351.051.731.400.35 %)a 70.340.962 (-36.131* 122.531 (-41.apoB % LDL-apoB Lb-LDL-C N-C 54.79 %)a % LDL-C Lb-LDL-apoB % LDL-apoB 71.121.970.02 .51 %)b 19.w.612 32.62 %)a 54.270.78 %)a 72.17 %)a 63.040.390.60 %)a 43.770.71 %)a 40.821 16.180† (-46.052 30. SMALL DENSE AND LARGE BUOYANT LDL SUBPOPULATION IN DMBA-INDUCED RATS AFTER TREATMENT Parameters LDL-C LDL.16 %)a 68.520.144 (+37.930.360.044 (-71.420.960.213 81.081 (-19.824 (-10.45 %)a 29.68 %)a 45. I-BdT.265* (+105.001.400.250.321 39.741.12 %)c 17.859 (+34. normal control.926 N-C.85 %)a %)a I-BdT 62.880.58 %)a 65.73 %)a 50.22 %)a 38.26 (+78.55 140.apoB Sd-LDL-C % LDL-C Sd-LDL.943 (+53.01 and cp<0.351.001.830.10 (-15.430.501.460.380.640.624 (-43.605 (-37.02 %)a 51.181 66.860.422 (+15.624 (-8. Significantly different from I-C at ap<0.825 (+30.192* (-47.640. I-C.350.62 (+58.060.616 (-44.086 (+267.832 36.019 (+83. Infected control.720. through orally in two equal doses of 2ml/Kg b.331.orally and I-BCOT.061 (-68.621.44 %)a 29.14 %)a 60.orally for 16 weeks.09 %)a 30.73 %)a %)a I-BCOT 57. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON PLASMA LDL. Significantly different from N-C at ap<0.022 (-13.120.

orally for 16 weeks. Significantly different from N-C at ap<0.2260.46 %)a 1.05 and dp<0.010 (-49.w. normal control.2530.030 Sd-LDL-C/HDL-C Lb-LDL/HDL-C 0.15 %)a 0.10 %)d 0.019 †For the calculation of ratios.700.150.029 (+50.019* (-65. *Values . bp<0.350.81 %)a I-BdT 2.400.075 (+141.82 %)a I-BCOT 2.790. I-C. Infected control.510.850.6410.37 %)b 0.034 (+118. N-C.006 1.034* (+128.6210.1160. Sd-LDL-C/HDL-C AND Lb-LDL/HDL-C IN DMBA-INDUCED RATS AFTER TREATMENT Group Ratio† N-C LDL-C/HDL-C 2.001.orally and I-BCOT.160.01.15 %)a 0.88 %)a HDL-C/TC 0.86 %)a 1.37 %)a 0.001 and bp<0.2800.024* (-67.67 %)b 3. are mean ± SD from pooled plasma of 15 rats in each group.001 (-48.54 %)a 2.004 (-81. 4 and 5. data is taken from Table 3.w. through orally in two equal doses of 2ml/Kg b. I-BdT.021* I-C 6.010. HDLC/TC. given through orally in two equal doses of 2ml/Kg b.8200.014 (-45.TABLE 5 EFFECT OF B.01. Significantly different from I-C at ap<0.029 (+308. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON THE RATIOS OF LDL-C/HDL-C.003 (-80.

020.35%)a Total Triglycerides cholesterol (mg /100mg (mg /100mg protein) protein) 0.240.004 (-8.652 (-8.081 12.85%)a 0.820.231 (+36.660.35%)a Free fatty acid (mg /mg protein) 21.043 (+28.02.530.210.860.025 (+82.001 (-12.05 and cp<0.006* (+26.40%)a Free fatty acid (mg /mg protein) 12.500. pooled lung or pooled kidney 15 rats in each group.5960.93%)a N-C I-C I-BdT 0. through orally in two equal doses of 2ml/Kg b. N-C.005 (+24.04 (+1.690.260.460.065 (-22.27%)a 24.16%)b 0.8660.85%)a 3.960.005 (+16.orally and I-BCOT.60%)a 23.143 13.6970. normal control.005 (+24.580.990. LUNG AND KIDNEY TRIGLYCERIDES.096 (-7.012 3. I-C.7580. TOTAL CHOLESTEROL AND FREE FATTY ACID CONTENT IN DMBA-INDUCED RATS AFTER TREATMENT Liver Lung Kidney Group Total Triglycerides cholesterol (mg /100mg (mg /100mg protein) protein) 0.003 2.960.720.5840. Significantly different from I-C at ap<0.001 and ep not significant.47%)a 3.021 (-34.820.11 2 (+51.066 4.6210.001.91%)a 0.6820.8240. Significantly different from N-C at ap<0.022 (-25.TABLE 6 EFFECT OF B.001* 0.003 (-18.76%)a I-BCOT 0.w.14%)a 0.260.13%)a 11.40%)a 9.78%)a Free fatty acid (mg /mg protein) 8.430.210.69%)a are mean  SD from homogenate of pooled liver.5960.5590.960.5650. Infected control.w. bp<0.orally for 16 weeks.003 0.6790.004* (-12.056 (-17.003 (-14.18%)a 11.093 (-14.56%)e Total Triglycerides cholesterol (mg /100mg (mg /100mg protein) protein) 0.045 (-21.005 (-12.22%)c 2.500.001.54%)a 10.410.54%)c 2.94%)a 2. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON LIVER.68%)a 2.27%)a 2.004* (-4.112 (-18.14 2 (-15. Significantly different from N-C at ap<0.49%)a 2.005 0.566 28.480.004 (-14. given through orally in two equal doses of 2ml/Kg b. I-BdT.98%)a 2. *Values .

through orally in two equal doses of 2ml/Kg b.110.w.820. I-BdT.024* (-52. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) FOR 16 WEEKS OF TREATMENT Group HMG-CoA reductase activity† 6. *Values .33 %)a N-C I-C I-BdT I-BCOT are mean  SD from homogenate of pooled liver of 15 rats in each group.TABLE 7 IN VIVO MODULATION OF HEPATIC HMG-CoA REDUCTASE ACTIVITY IN DMBA-INDUCED RATS TREATED WITH B.960.52 %)a 4.w.082* 3. Significantly different from I-C at ap<0. Significantly different from N-C at ap<0.001. given through orally in two equal doses of 2ml/Kg b. normal control.orally and I-BCOT.067* (+54.orally for 16 weeks.550.036* (+27.98 %)a 3. I-C. Infected control.001. N-C.

015 (+51.056* 9. .orally and I-BCOT.044 (-18.820.11 %)a 3.006 (-18.890. Significantly different from N-C at ap<0.w.210.081 I-C 36.510.990.34 %)a 42.810.w.370.23 %)a 13.016 (+54.024 (-16. N-C.240.420.200.80 %) a 4.TABLE 8 ANTIOXIDANT IMPACT OF B.73 %)a 46.24 %)a 12. I-C.01 %)a 5.44 %)a 4.460. Infected control.014 (-13.orally for 16 weeks.020* (+14.011 2.12 %)b 14.910.79 %)a 3.100.120.121* (-23.57 %)a I-BdT I-BCOT *Values are mean (µmole/dl) ± SD from pooled plasma of 15 rats in each group. LIPID HYDROPEROXIDE AND MALONDIALDEHYDE CONTENT IN DMBA-INDUCED RATS AFTER TREATMENT Group Total antioxidants Conjugated diene Lipid hydroperoxide MDA N-C 48. Significantly different from I-C at ap<0.310.116 (+72.022 (-8.032 3. I-BdT. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON PLASMA TOTAL ANTIOXIDANTS.360.05. CONJUGATED DIENE. through orally in two equal doses of 2ml/Kg b. normal control.034* (+25.00 %)b 3.062 (-15.001. given through orally in two equal doses of 2ml/Kg b.001 and bp<0.

9780.015* (+33.035 (-13.024 (-16.054 0.80%)a 2.41%)a 3.011* (-20.004 (-30.120.54%)a 1.740.5650.026 (-19.021* 1.022 (-10.7540.054* (-21.03%)d 2. .044 (-20.990.011 0. normal control. N-C.016 (+32.70%)a 3.02.001 and cp<0.320.34%)a 2.590.003 (+43.520.840.4460.170.39%)a I-BdT 6.024 2.006 (-27.240.025 (+47.280.4850. Significantly different from N-C at ap<0.66%)a 4.01 0 (11.240.084 (+27.06 0 5.800.014 2.500. LUNG AND KIDNEY CONJUGATED DIENE.020 (-16.420.64%)c I-C 8.580.02 0 (+36.012 (+57.610.580.200. Significantly different from I-C at ap<0.160.26%)a 3.66%)a 2.066 (-22.77%)a 0.51%)a 1.5850.35%)a *Values are mean (nmole/mg protein) SD from homogenate of pooled liver.034 (+28.58%)a 0.5100.011 (-8.54%)a 0.07%)a 3.9630.010.5260. LIPID HYDRPEROXIDE AND MALONDIALDEHYDE CONTENT IN DMBA-INDUCED RATS AFTER TREATMENT Liver Group Conjugated diene Lipid hydroperoxide Lung Lipid hydroperoxide Kidney Lipid hydroperoxide MDA Conjugated diene MDA Conjugated diene MDA N-C 6.004 4.034 (-15.27%)a 0. I-BdT. through orally in two equal doses of 2ml/Kg b. Infected control.180.002 (-22.001.001 3.100.45%)a 0.90%)a 5.2120.TABLE 9 EFFECT OF B.7020. given through orally in two equal doses of 2ml/Kg b.w.58%)a 4.45% )a 5.56%)a 3.43%)d 0.03 1 (-8. pooled lung or pooled kidney 15 rats in each group.w.35%)a 3. I-C.02 3.001 (+47.002 (-11.91%)a I-BCOT 6.610.003 (-25. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON LIVER.210.55%)a 2.4980.orally and I-BCOT.orally for 16 weeks.

18%)a 0.0021 0.5260.18%)a 7.70%)a Liver (U/mg protein)‡ 0.0060 (-36.23%)a Lung (U/mg protein)‡ 0. through orally in two equal doses of 2ml/Kg b. N-C.6360. I-C.152* (-23.3920. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON PLASMA. pooled lung or pooled kidney of 15 rats in each group. Significantly different from N-C at ap<0.5220.89%)a 0.0011 (+154.660.1790.40%)a 0.68%)a 0.110.86%)a 7.TABLE 10 B.001.0012 (-8.52%)a 0. Infected control.040.orally for 16 weeks.6120.0010 (+46.w.0012 (-16.021* 10.0025 (+38.4560.orally and I-BCOT.001.2880.126* (+58. given through orally in two equal doses of 2ml/Kg b.7120.0042 (-36.0011 0.84%)a I-BdT I-BCOT are mean  SD homogenate of pooled liver.116* (-29.0011 0.2900.0021 (-9.75%)a 0. LIVER. *Values . normal control.0016 (-25.5750. I-BdT.22%)a Kidney (U/mg protein)‡ 0. LUNG AND KIDNEY XANTHINE OXIDASE ACTIVITY IN DMBA-INDUCED RATS AFTER TREATMENT Xanthine oxidase activity Group Plasma (U/ml)† N-C I-C 6. Significantly different from I-C at ap<0.320.w.8500.

022 (+11.74 %)a Lung Catalase (U/mg protein)† Superoxide dismutase (U/mg protein)‡ 2.003 (+20.004 (-10.450.1560.9350.89 %)a 3.110.120.42 %)a 0.033 (-9.270.230.10 %)a 2.7700.95 %)a (+15.054 (+5. pooled lung or pooled kidney of 15 rats in each group.062 2.022* (+24.8830. Significantly different from I-C at ap<0.orally for 16 weeks.004 (+14. Infected control.01.11 %)a 4.510.58 %)a are mean  SD from PMS fraction of pooled liver.220.73 %)b 2.002 (+56.65 %)a 2.21 %)a 3. *Values .400. N-C. I-C.9320.8540.34 %)a 0.005 (+17.36 %)a Superoxide dismutase (U/mg protein)‡ 0.004 (+13. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON LIVER.w.680.042 0.142* 3.64 %)a (+16.001 and bp<0.w. LUNG AND KIDNEY CATALASE AND SUPEROXIDE DISMUTASE ACTIVITIES IN DMBA-INDUCED RATS AFTER TREATMENT Liver Catalase (U/mg protein)† Superoxide dismutase (U/mg protein)‡ 0.05.500.001 and bp<0.1400.166 0.7870. Significantly different from N-C at ap<0.95 %)b Group N-C I-C I-BdT I-BCOT 4.9240.223* (-29.005 (+59.06 %)a 4. given through orally in two equal doses of 2ml/Kg b.002 (-23.004 0.006 1. normal control.121* (+27.320. I-BdT.540.56 %)b 2.002 (-13.TABLE 11 IMPACT OF B.orally and I-BCOT.560.154 2. through orally in two equal doses of 2ml/Kg b.76 %)a 2.6540.002 0.8020.50%)a Kidney Catalase (U/mg protein)† 3.052 (-35.

380.31%)a 63.46%)a 10. N-C.21* 13.142 (+131.07%)a 14.26%)b 60.520.040.200.80%) a 45. Significantly different from I-C at ap<0.300.180.750.w.512. I-C. Significantly different from N-C at ap<0. through orally in two equal doses of 2ml/Kg b. normal control. FREE AND PROTEIN-BOUND -SULFHYDRYL CONTENTS OF GLUTATHIONE IN DMBA-INDUCED RATS AFTER TREATMENT Liver Group Total-SH Free-SH Lung Kidney Proteinbound-SH 64. I-BdT.603 (+146.130.181.442 (-68.604 (-53.74%)a *Values are mean (nmole SH group/mg protein) SD homogenate of pooled liver.580.064 (+39.116 (-9.52%)a 13.32%)a 15.146 (+13. LUNG AND KIDNEY TOTAL.406 10. pooled lung or pooled kidney of 15 rats in each group.w.17%)a 12.114 (+160.61%)a 52.05.670.610.16%)a 41.10 Total-SH Free-SH Proteinbound-SH 56.700.62* (+93.082 I-C 37.228 (+125.45%)a I-BCOT 70.564 (+129. .TABLE 12 IMPACT OF B.160.650.65 %)a 22.104 58.860.314 66.45%)a I-BdT 72.46* (-51.262 (+8.080.071 (-16. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) ON LIVER.821.054 (+45.627 (-60. Infected control.75%)a 13.401 N-C 76.310.520 (+118.78%)a 9.050 (+1.180.800.611 (+186.45 (+67.421.561 12.26%)a 23. given through orally in two equal doses of 2ml/Kg b.110.521.730.60%)a 52. 462 (-59.06)a 56.39%)a 10.448 (-60.76%)a 16.020.026 (-12.102 (+126.438 (+102.310.39%)a 31.03%)a 48.104 (+52.110.901.180.060.600.98%)b 51.001 and bp<0.63%)a 59.40* (+88.67%)a 12.orally for 16 weeks.870.558 Total-SH Free-SH Proteinbound-SH 50.001.460.orally and I-BCOT.820.27%)a 26.

06 (+20.28%) .630.02 (+38.081 104.169 (+23.880.24 %)a 93.311.465 (+49.240. Infected control.32%)a 102.220.11 (-23.08* (-23.82%)a 78.611.241.orally and I-BCOT. given through orally in two equal doses of 2ml/Kg b.58%)a 15.022 (+38.95%)a 54.261. N-C.160.621.001.961.w. LUNG AND KIDNEY GLUTATHIONE PEROXIDASE.211.321.35)a 10.221.430.461.230.52 %) a 63.140.980.44 %)a 11.680.01 Glutathione peroxidase (U/ mg protein )† Glutathione reductase (U/ mg protein )‡ transferase (U/mg protein)# Glutathione peroxidase (U/ mg protein )† Glutathione reductase (U/ mg protein )‡ Glutathione -Stransferase (U/mg protein)# 93.621.orally for 16 weeks. pooled lung or pooled kidney of 15 rats in each group.112 (-22.880.28%) a 92. are mean  SD from homogenate of pooled liver. I-BdT. Significantly different from N-C at ap<0.081 (+48.40%)a 117.36 (-39.218 (-23.41 (+49.63 (+36.93%)a 84.28%)a 62.452 (-32.22%)a 56.641 13.06 N-C 58.96 %)a 92. GLUTATHIONE REDUCTASE AND GLUTATHIONE-S-TRANSFERASE ACTIVITIES IN DMBA-INDUCED RATS AFTER TREATMENT Liver Group Lung Kidney Glutathione-S- Glutathione peroxidase (U/ mg protein)† Glutathione reductase (U/ mg protein)‡ Glutathione -Stransferase (U/mg protein)# 135.11 (-39. normal control.07%)a 63.140 I-C 72. through orally in two equal doses of 2ml/Kg b.45%)a 12.66 10.88%)a 10.03%) a 10.631.20%)a 55.93%)a 123. Significantly different from I-C at ap<0.121 (-9.864 (-21.616 (+29.42* (+24.690.860.26%)a I-BdT I-BCOT 86.27 %)a 87.001.151 (+26.59 (+12.360.221.261. *Values .990.81* (-24.08 (+21.360.26 (+39.481.TABLE 13 B.55 62.670.001. I-C. Significantly different from N-C at ap<0.86%) a 123.251 (-32.w.481.17%)a 14.22 (+19.961.06* 10. DIFFUSA (I-BdT) AND BLACK CARAWAY OIL (I-BCOT) MEDIATED EFFECT ON LIVER. pooled lung or pooled kidney and PMS fraction of pooled liver.87%)a 7.620 (-20.78%)a 8.213 104.960.521.

Section shows the damage hepatocytes and various size vacuoles (bend arrow). The damage is recovered with the treatment of Black Caraway Oil (I-BCOT).3. The normal histological section shows the well arranged cells and clear central vein.C. Section shows the complete destruction of hepatocytes degeneration of central vein. Histopathological liver changes are restored near to normal in the B.3. B.A B Fig. C D Fig. Histological and morphological studies of 16 weeks experimental rat liver. A. . diffusa (I-BdT) treated group and D. fatty degeneration and neutrophil distribution.

The damage kidneys are recovered with the treatment of I-BdT and I-BCOT.C&D. C D Fig. . B.4. Histological and morphological studies of 16 weeks experimental rat kidney. The normal kidney section shows the well arranged cells. A.A B Fig.4. Carcinogenic group shows the enocytic vacuoles as characteristically seen in proximal tubules and the thicking of the glomerular basement with glomerulosclerosis (arrow).

C&D. Pancreatic section of normal rat shows cells with well preserved cytoplasm and nucleus. .A B Fig. not well defined and defect in cell membrane. the cells are irregular. In the pancreatic section of DMBA-Induced rats. B. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) treatment were improved restored the altered pancreatic Histopathological changes. B. C D Fig. Histological and Morphological studies of 16 weeks experimental rat pancreas.5.5. A. Necrosis of the cells is very clear.

. plasma and lipoprotein lipids including cholesterol and apoB content of LDL and its subfractions and antioxidant enzymes. hemoglobin. were reflected on a variety of parameters. that occurred in rats. such as.DISCUSSION: Hypercholesterolemia is firmly established as a primary risk factor for atherosclerotic cardiovascular disease. In this present investigation we tried to examine the effect of B. The DMBA-Induced extensive proatherogenic changes. significantly reduced the overall oxidative burden and effectively the above altered parameters. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) supplementation on overall proatherogenic actions of DMBA-Induced carcinogenesis we found that in the white albino rats DMBA-Induced inflated oxidative stress hypercholesterolemia and carcinogenesis when compared with normal control rats. Supplementation of infected rats with B. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) for treatments.

42 µM) in comparison to BCO (38. diffusa (44. B. Both B. The reduction in the free radical quenching efficiency of B. diffusa was found more efficient scavenger of peroxyradical then Black Caraway Oil.They quench free radicals in cell membranes and protect them against lipid peroxidation.11 µM). (Fig 2. . The higher antioxidant potency of B. the results demonstrate that a DMBA-Induced a severe hyperlipidemia in I-C rats as compared to normal control (NC).2) Consistent with the results from infected rats (Table 1). rats DMBA-Induced also exhibited significant decrease hemoglobin. diffusa (Bd) as compared to Black Caraway Oil (BCO). diffusa (I-BdT) and Black Caraway Oil (I-BCOT) were equally effective in increasing (18-22 %) the hemoglobin.

diffusa treatment not only blocked the minimal decline of 14 % seen in HDL-C level of I-C rats but increased it to a level. to 42 % and 35 % higher than normal control HDL3 value. from a reduced value of only 4 % in I-C rats. These results demonstrate that both B. On the other hand. 45 %) levels contributed to the increased degree of hyperlipidemia in I-C rats. B. the cholesterol content of more antioxidative small. . 21 % higher than normal control value. LDL-C and atherogenic non-HDL-C concentrations in I-C rats were significantly reduced to a level close to their counterparts in N-C rats. Highly increased plasma TG. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) exert a potent effect in normalizing the high levels of TG as well as atherogenic non-HDL-C in DMBA-induced hyperlipidemia in rats. atherogenic HDL-C was decreased by only 14 %. VLDL-C. in I-C rats. In complete contrast to infected rats.A much higher increase in plasma TG (111 % and atherogenic non-HDL-C (99 % vs. after treatment of B. On the other hand. indicating a very mild dyslipidemia in I-C rats. in comparison to a decline of 49 % in I-BCOT. TC. dense HDL3 was increased. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) treatment.

LDL-C/HDL-C. vs. HDL-C/TC. lung and kidney lipid levels is consistent with a significant increase (52 %) in liver HMG-CoA reductase activity of I-C rats (Table 7). indicating an excellent normalization of highly atherogenic sd-LDL-C and LDL-C. + 308 % and + 51 %.49 %. . while treatment with B. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) fully normalized these altered ratios to a level. corresponding ratio values in N-C). 20 % to 25 % better than their counterparts in N-C.Consistent with these findings. The significant increase in plasma. . liver. respectively. providing a mechanism for the reduction of plasma and tissue lipids. Treatment of I-C rats with dietary B. thus. in I-C rats (Table 5). diffusa (I-BdT) and Black Caraway Oil (I-BCOT) was associated with a significant decrease in hepatic HMG-CoA reductase activity. which was restored to 55 % and 52 % of N-C value. sd-LDL-C/HDL-C and lb-LDLC/HDL-C ratios were markedly altered (+ 128 %.

diffusa (IBdT) and Black Caraway Oil (I-BCOT). lung and kidney of I-C rats (Table 13). The degree of irregularity of the nucleus was reported to be related to the degree of malignancy of the cells or to the extent of damage . particularly the nuclei. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) administration significantly blocked this increase in XO activity and reduced it to a level close to corresponding normal control values. lung and kidney XO activity of DMBAInduced rats. In addition. reduction of GST activity may also be due to decreased levels of GSH in tissues. liver. A similar decrease in hepatic CAT and SOD activities B.Our results show a significant increase in plasma. Our results show a decline in GSH (Table 12). diffusa and Black Caraway Oil feeding of I-C rats significantly reduced the FFA and lipid peroxidation products. Gred and GST activities and an increased GPx activity in liver. kidneys and pancreas from rats treated with DMBA treatment with revealed damage to the cells. B. since GSH also acts as substrate and co-substrate in essential enzymatic reactions of Gpx and GST. and increased the CAT and SOD activities in liver. lung and kidney. and reversed these parameters to near normal levels (Table 11). Histological examination of livers. These results indicate a potent free radical scavenging property of both B.

However. certain other compounds of DMBA-Induced. diffusa supplementation and Black Caraway Oil similarly. . which were reversed to 20 % of respective control values of age-matched normal control (N-C). a modest and significant increase in plasma total lipid and atherogenic non-HDL-C levels in infected rats (I-C). Our results showed that due to sustained free radical.SUMMARY AND CONCLUSION Several epidemiologic studies have established a strong and consistent link between DMBA-Inducing and increased cardiac morbidity and mortality. which were significantly reversed to 42-98 % of normal control (N-C) value after treatment of B. including a significant increase in atherogenic non-HDL-C. diffusa treatment of infected rats resulted in a significant increase hemoglobin levels. DMBA-Induced infected rats (155-182g) exhibited several proatherogenic actions. cholesterol content of more antioxidative HDL3 was not affected during of B. Other studies show that in addition to substantial increase in oxidative stress. This may be due to markedly increased production of oxidants and significantly diminished antioxidant defense including a decline in total plasma antioxidants. HDL2 and HDL3. diffusa treatment. B. Our results show that in comparison to normal control (N-C). with a concomitant decline in the cholesterol concentrations of antiatherogenic HDL and its subfractions.

. Treatment of I-C rats with dietary B. diffusa and Black Caraway Oil treatment of I-C rats was associated with a significant decreases in TG. lung and kidney were also observed. a significant increase in these lipids of liver. While. which may provide a mechanism for the reduction of plasma and tissue lipids. diffusa and Black Caraway Oil was associated with a significant decrease in plasma and tissue lipid levels as well as hepatic HMG-CoA reductase activity. FFA and TC levels of I-C rats. FFA and TC levels of liver. These results demonstrate that sustained oxidative stress in I-C rats is also able to induce hyperlipidemia in the above tissues with a maximum increase in hepatic TC. FFA and TC of each tissue. lung and kidney close to corresponding normal control values.Consistent with the increase in plasma TG. which was restored to 55 % and 27 % of N-C value. B. diffusa and Black Caraway Oil effectively blocked these increases and restored the TG. while both B.

and post-initiation stages. Consistent with morphological and histological examinations. Morphological and histological examination of liver. particularly the nuclei. LDL-C and apo-B levels. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) to rats. revealed damage to the cells. kidney and pancreases from rats treated with DMBA. diffusa (I-BdT) and Black Caraway Oil (IBCOT). we have investigated the anti-tumour activity of I-BdT and I-BCOT in experimental carcinogenesis of liver. was associated with a significant decline in the above lipid parameters. . Feeding of B. total cholesterol.Based on strong hypolipidemic and antioxidant properties of B. which evident from the appearance of multiple tumours on greyish white patches on the liver of the carcinogen treated rats. Treatment with DMBA resulted in the formation of neoplastic nodules. elevated the carcinogen treated rats are indicative of the severity of liver. kidney and pancreases. DMBA. during pre. which is known to induce hepatic carcinogenesis and hypercholesterolemia. As expected. administration of DMBA causes a significant increase in plasma triglycerides. We have utilized the carcinogen. lung and kidney carcinogenesis.

. diffusa and Black Caraway Oil. in liver. significantly reversed/restored the altered tissue activities of SOD. SOD. lung and kidney of infected rats. catalase. SOD. oxidant stress may be increased owing to a higher production of ROS. Gred and GST including total. which are controlled by antioxidant enzymes. diffusa and Black Caraway Oil mediated a near normalization of peroxide levels and scavenging enzyme activities as well as GSH in liver. Gred. An impaired radical scavenger function has been linked to decreased/increased activity of enzymatic and nonenzymatic antioxidants. Gred and GSH. Both B. except Gpx activity which was significantly increased. free and protein bound-SH contents of glutathione. CAT. Gpx. indicating an almost total alleviation of oxidative damage by these antioxidants. Our results show a significant decrease in the activities of antiperoxidative enzymes. indicating a strong antilipid/lipoprotein peroxidative effect of these hypolipidemic and anticarcinogenic agents. lung and kidney of DMBA-Induced rats. GST as well as GSH.It is well known that DMBA-Inducing is associated with a substantial increase in oxidative stress. catalase. to near normal control values. Treatment of DMBA-Induced hyperlipidemic rats with B. Gpx.

based on B. no side effects and a good source of antihypercholesterolemic. daily use of dietary B. In addition. diffusa (I-BdT) and Black Caraway Oil (IBCOT) feeding did offer a significant protection and did reduce the severity and extent of neoplastic transformation during both initiation and/or promotion in the liver and kidney of experimental carcinogenic rats. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) treatment. described in the present study. diffusa and Black Caraway Oil will be efficacious. antioxidant actions and anticarcinogenic may be useful in the prevention and treatment of DMBA-Induced hyperlipidemia/ and atherosclerosis. Daily use of B. antioxidant actions and anticarcinogenic. The dual chemotherapeutic properties of B. cost effective.The combined results provide evidence that analysis of marker enzymes. in addition to its anti-cancer and antioxidant impacts. lipid peroxide and examination of gross morphology and histology suggested that B. GST. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) by normal population will prevent the occurrence of hypercholesterolemia and cardiovascular diseases as well as initiation and promotion of certain forms of cancer. thus limiting the availability of mevalonate-derived products required for cholesterol production and tumour growth. diffusa (I-BdT) and Black Caraway Oil (I-BCOT) in atherosclerosis and cancer are apparently mediated by reducing HMG-CoA reductase. also exerted a strong hypocholesterolemic action. B. daily intake of Black Caraway Oil as a dietary supplement by hypolipidemic /antiatherogenic /antihypercholesterolemic. In conclusion. . diffusa mediated multiple therapeutic benefits. indicating a linkage between atherosclerosis and cancer.

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