Pharmaceutical Biology

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Nephroprotective Action of Phoenix dactylifera. in

Gentamicin-Induced Nephrotoxicity

A. A. Al-Qarawi, H. Abdel-Rahman, H. M. Mousa, B. H. Ali & S. A. El-Mougy

To cite this article: A. A. Al-Qarawi, H. Abdel-Rahman, H. M. Mousa, B. H. Ali & S. A. El-Mougy

(2008) Nephroprotective Action of Phoenix�dactylifera. in Gentamicin-Induced Nephrotoxicity,
Pharmaceutical Biology, 46:4, 227-230, DOI: 10.1080/13880200701739322

To link to this article: https://doi.org/10.1080/13880200701739322

Published online: 07 Oct 2008.

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Pharmaceutical Biology
2008, Vol. 46, No. 4, pp. 227–230

Nephroprotective Action of Phoenix dactylifera in

Gentamicin-Induced Nephrotoxicity

A. A. Al-Qarawi,1 H. Abdel-Rahman,2 H. M. Mousa,1 B. H. Ali,1 and S. A. El-Mougy1

1
Department of Veterinary Medicine, Faculty of Agriculture and Veterinary Medicine, AlQaseem University, Buraydah,
Saudi Arabia; 2 Physiology Department, Fac. Vet. Med. (El-Sadat Branch), Menofia University, El-Sadat City, Egypt

Abstract nephrotoxicity, including dietary components (Ali, 1995).

It is established that protein is one of the risk factors as-
We investigated the effect of an extract of the flesh and
sociated with GM nephrotoxicity (Whiting, 1988) It has
pits of dates [Phoenix dactylifera L (Arecaceae or Palmae)]
also been reported that iron supplementation in the diet
on gentamicin (GM) nephrotoxicity in rats. The animals
aggravates GM-induced nephrotoxicity in rats (Kays et al.,
were given either the date flesh extract mixed with the food
1992). On the other hand, inclusion of fish oil (Ali & Bashir,
(50% w/w) or the pits extract mixed in the drinking water
1994), ascorbic acid (Ben Ismail et al., 1994), and vitamin
(2:1 w/v), and GM (80 mg kg−1 day−1 intramuscularly for 6
E (AbdelNaim et al., 1999) ameliorates biochemical and
days) was injected during the last 6 days of treatment. Other
histologic signs of GM nephrotoxicity.
groups of rats were given GM concomitantly with the date
In view of its high nutritional content, date flesh has been
flesh extract or the date pits extract at the above doses. GM
used as an important dietary item in North Africa, Arabia,
treatment significantly increased the plasma concentrations
Persia, and some other parts of the Old World since ancient
of creatinine and urea and induced a marked necrosis of
times. In some countries, the date pits are used crushed as
the renal proximal tubules. The date flesh and pits were
an animal feed and as a hot drink instead of coffee.
effective in significantly reducing the increases in plasma
The flesh and pits of dates have recently been investi-
creatinine and urea concentrations induced by GM nephro-
gated for their possible medicinal and nutritional benefits.
toxicity and ameliorating the proximal tubular damage. An-
The scientific basis of their benefit has started to be inves-
tioxidant components in the date (e.g., melatonin, vitamin
tigated. Recently, it has been shown that date flesh has a
E, and ascorbic acid) were suggested to be the basis of the
strong in vitro antioxidant (Vayalil, 2002) and immunos-
nephroprotection.
timulant effect (Puri et al., 2000). There is a popular belief
in our region that consumption of date flesh each morning
Keywords: Date palm, gentamicin, nephroprotection, helps in antagonizing the actions of toxic materials. The
nephrotoxicity, Phoenix dactylifera L. current work is one of a series of studies on the chemical
constituents and pharmacological actions of date flesh and
pits.

Introduction Materials and Methods

Gentamicin (GM) is a useful aminoglycoside antibiotic
against serious and life-threatening infections caused by
Gram-negative and/or Gram-positive bacteria. However, it
has been reported that some signs of renal impairment are
observed in up to 30% of patients treated with the drug
for more than 7 days (Mathew, 1992). Several investigators
have studied the factors that may influence GM-induced
Animals
Thirty-six adult male Wistar albino rats weighing between
400 and 450 g were used in this work. They were kept at
a controlled temperature of 25 ± 2◦ C, relative humidity
of 60–80%, and a light regimen of 14 h light:10 h dark
(lights on at 0600). General procedures for animal care and
housing were in accordance with the U.S. Department of

Accepted: August 30, 2007.

Address correspondence to: Hassan Abdel-Rahman, Physiology Department, Faculty of Veterinary Medicine, Menofia University, El-Sadat
City, Menoifa Province, Egypt; Email: habdelrhman@hotmail.com

DOI: 10.1080/13880200701739322 
C 2008 Informa Healthcare USA, Inc.
228 A. A. Al-Qarawi et al.
Agriculture through the Animal Welfare Act (7USC 2131)
1985 and Animal Welfare Standards incorporated in 9 CFR
Part 3, 1991. Pelleted Purina chow and water were given
ad libitum.
Plant material, preparation, and administration
The fruit of Phoenix dactylifera L (Arecaceae or Palmae)
was obtained from the date manufacturing plant in Buray-
dah, Al-Gaseem district, and classified in the Department
of Botany, Faculty of Science, King Saud University, Saudi
Arabia. Voucher specimens of the plant were deposited in
the Department of Veterinary Medicine, Faculty of Agricul-
ture and Veterinary Medicine, Bureidah University, Saudi
Arabia. The date flesh was separated from the pits, and the
flesh was soaked in distilled water (in the ratio of 1:2 w/v)
for 48 h at 4◦ C. The extract was then thoroughly mixed
with Purina chow, as a 50% w/w mixture, and given as a
daily supply of food during the experimental period. The
pits were washed free of any flesh, air-dried, and powdered.
The powder was then soaked in cold distilled water (4◦ C)
for 48 h in a ratio of 2:1 (w/v). The pit extract was given as
the only source for drinking.
Toxicity testing
A separate experiment was performed to determine whether
any toxic effects were produced by the aqueous extracts.
The rats were fasted for 12 h and randomly divided into
drug-treated test groups and vehicle-treated control group
making up seven groups of six rats per cage. The aque-
ous flesh and pit date extracts (100, 200, 400, 800, 1600,
and 3200 mg/kg body weight) were separately administered
orally to the rats in each of the test groups. Each of the rats
in the control groups was treated with vehicle alone (DMSO
0.5%; 1 mL/kg body weight). The rats in both the test and
control groups were allowed access to food and water, and
behavioral changes were observed over a period of 24 h to
21 days for signs of acute or chronic toxicity. The mortality
number caused by the extracts within this period of time
was observed. Log dose-response plots were constructed
for each extract, from which the median lethal dose (LD50 )
of the extracts was determined (Lorke, 1983).
Treatments
The rats were randomly divided into six equal groups as
follows:
Group 1: The animals were given Purina chow (100%
w/w) for 28 consecutive days. During the last six
days of the feeding period, normal saline was in-
jected intramuscularly (i.m.) (2 mL kg−1 day−1 for 6
days). Rats were sacrificed 24 h after the last injection
(day 29).
Group 2: Rats were given Purina chow (100% w/w) for
6 days, and were concomitantly injected during this
period with GM (80 mg kg−1 day−1 for 6 days). Rats
were sacrificed 24 h after the last dose (day 7).
Group 3: The animals were given Purina chow mixed with
the date flesh (50% w/w) for 28 consecutive days. Dur-
ing the last 6 days of the feeding period, GM was
injected i.m. (80 mg kg−1 day−1 for 6 days). Rats were
sacrificed 24 h after the last dose (day 29).
Group 4: Rats were given Purina chow mixed with the date
flesh (50% w/w) for 6 days. During this period, rats
were injected with GM (80 mg kg−1 day−1 for 6 days).
Rats were sacrificed 24 h after the last dose (day 7).
Group 5: The animals were given the aqueous date pits
extract as the only source of drinking fluid for 28 con-
secutive days. During the last 6 days of the treatment
period, GM was injected i.m. (80 mg kg−1 day−1 for 6
days). Rats were sacrificed 24 h after the last dose (day
29).
Group 6: Rats were given the aqueous date pits extract
as the only source of drinking fluid for 6 consecutive
days, concomitantly with GM (80 mg kg−1 day−1 for 6
days). Rats were sacrificed 24 h after the last dose (day
7).
Injections of GM were made daily at 0800 to minimize
the circadian variation in nephrotoxicity (Pariat et al., 1988).
At the end of treatment, all animals were rapidly stunned
and decapitated. Blood samples were taken from the trunk
over heparin, centrifuged (900 ×g for 15 min at 5◦ C), and
the plasma was separated and stored at −5◦ C until analysis.
Biochemical assay
Plasma creatinine and urea were determined by automated
spectrophotometric methods (BM/Hitachi autoanalyzer-
911; Boehringer Mannheim, Germany) according to the
instructions of the manufacturer.
Drugs and chemicals
Gentamicin sulfate was a gift from the Saudi Pharmaceu-
tical Company (Buraydah, Al Gaseem, Saudi Arabia). The
kits were obtained from Boehringer Mannheim.
Statistical analysis
Recorded values are means ± SEM (n = 6). The signifi-
cance of differences was estimated using the Student’s t-
test. p values less than 0.05 were considered significant.
Results
Oral administration of graded doses of the aqueous extracts
of the date flesh and pits to male Wistar rats, in our acute
 Nephroprotective and Phoenix dactylifera 229

Table 1. Effect of date flesh and pits aqueous extracts before and after treatments on gentamicin-induced nephrotoxicity changes in creatinine
and urea in plasma of rats (n = 6).

Creatinine Urea
Body Change in Kidney Kidney weight concentration concentration
Treatment weight (g) weight (%) weight (g) (% body weight) (mg/dL) (mg/dL)

Group 1 Olive oil (5 mL/kg) + 426.7 ± 0.87b 0.07 2.98 ± 0.02a 0.70 ± 0.01 0.53 ± 0.016b 21.03 ± 0.97 b
saline (2 mL/kg)
Group 2 Olive oil (5 mL/kg) + 406.0 ± 4.34c 0.05 2.95 ± 0.02a 0.71 ± 0.02 1.23 ± 0.057 a 58.60 ± 2.24 a
gentamicin (80 mg/kg)
Group 3 Palm flesh (28 days) 452.17 ± 3.84a 2.96 ± 0.02a 0.53 ± 0.016 b 21.98 ± 1.65 b
Group 4 Palm flesh (6 days) 456.33 ± 3.30a 2.93 ± 0.01a 0.59 ± 0.03b 22.32 ± 1.62b
Group 5 Palm pits (28 days) 426.17 ± 2.02b 2.98 ± 0.03a 0.56 ± 0.012b 23.16 ± 0.84 b
Group 6 Palm pits (6 days) 424.00 ± 0.01b 2.97 ± 0.02a 0.63 ± 0.04b 23.83 ± 0.91b

Means having different superscripts are significantly different at p < 0.01.

and chronic toxicity study, did not produce any toxicity.
Based on this observation, the extracts were considered to
be safe in mammals.
The results are shown in Table 1. Treatment with the
aqueous extract of the palm flesh resulted in an increase
in the body weight of the animals during the treatment pe-
riod. Pretreatment with the date flesh aqueous extract also
induced a prophylactic action on GM-induced nephrotox-
icity in the rats as evidenced by a significant decrease in
the plasma concentrations of creatinine and urea. The same
effect was seen when the palm flesh aqueous extract was
given in conjunction with GM, resulting in a curative effect
ameliorating the nephrotoxic action of GM.
Treatment with the palm pits did not affect the body
weight of the animals. However, it showed a protective role
against nephrotoxicity when given before and together with
GM.
Discussion
The increase in the body weight of the animals fed with the
date flesh aqueous extract could be attributed to the rich
constituents seen in the form of sugar contents amounting
to 70% of its weight (Fayadh & Al-Shwoiman, 1990).
GM nephrotoxicity is, at least partially, attributed to the
generation of free radicals, enhanced lipid peroxidation, and
decreased glutathione (GSH), in the kidney (Ramsammy et
al., 1985; Walker & Shah, 1988; Ali et al., 1992). It is
reasonable, therefore, to suggest that the observed nephro-
protective action of the date flesh and pits may be due to an
increase in activity of the free radical scavenging enzymes
or counteraction of the free radicals. Date flesh and pits
have recently been shown to possess strong antioxidant ac-
tions (Vayalil, 2002). Some of the constituents of dates have
been shown to act as antioxidants. We have recently demon-
strated the presence of melatonin, vitamin E, and ascorbic
acid in date flesh and pits (AlQarawi et al., unpublished
data). Melatonin was discovered to be a direct free radical
scavenger (Reiter et al., 2000; Karbownik et al., 2001). The
work carried out by AbdelNaim et al. (1999) indicated that
the antioxidant activity of vitamin E initiated a potential
protective effect against gentamicin-induced nephrotoxic-
ity through its inhibition of lipid peroxidation. Ben Ismail
et al. (1994) found that ascorbic acid, in a moderate dose
(100 mg/kg), acted as an antioxidant reducing lipid per-
oxidation and, thus, induced a protective role against the
GM-induced nephrotoxicity. It is of interest to point out
that a recent investigation carried out by AlQarawi et al.
(2005) indicated that the chemical composition of the dates
was implicated in a protective role against gastric ulcer
through an anti-oxidant action.
In conclusion, this work has shown that date flesh and pits
extract possess substances that may have protective action
against GM nephrotoxicity in rats.
Acknowledgments
This work was supported by a research grant from the Col-
lege Research Board. Thanks to Professor S. Al Yahya for
his interest and support of this project, and Al Gaseem Date
Factory for providing free samples of dates for this study.
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