See discussions, stats, and author profiles for this publication at: https://www.researchgate.

net/publication/264496947

Honey and Male Reproductive Health. In: Honey: Current Research and
Clinical Applications. Nova Science Publishers, ISBN 978-1-61942-656-6, pp
131-142

Chapter · January 2012

CITATIONS READS

0 927

1 author:

Mahaneem Mohamed
Universiti Sains Malaysia
130 PUBLICATIONS   863 CITATIONS   

SEE PROFILE

Some of the authors of this publication are also working on these related projects:

Diabetes mellitus and male reproductive function View project

Nutritional supplement, health and sports performance View project

All content following this page was uploaded by Mahaneem Mohamed on 06 August 2014.

The user has requested enhancement of the downloaded file.

ln: Honey: Current Research and Cljnical Applications ISBNr 978,1-61942-656-6
Editor: Juraj Maitar O 2012 Nova Science Publishers, tnc.

Chapter VIII

Honey and Male Reproductive Health

Mshaneem Mohamedr
Department of Physiology, School of Medical Sciences, University
Sains Malaysia, Kubang Kerian, Kelantan, Malaysia

Abstract
Honey, a natual product ofhoncy bees, is traditionally consumed fo. enhancement
of feiility and vitaliq, among males in some popularions. The decline in mate
reproductive health and fedility for the pasr 30 years has been linked to environmental
toxicanis. This has led to ihe increased interest ro investigate rhe possible beneficial effect
ofhoney on male reproductive health. A few experimental studies have been done aod
rhe aim of this review is to summarize and discuss these studies particularly rclared ro
oxidative stress and cigarette smoke exposu.e. How€ver, more srudies are needed to
investigate its exact mechanism ofaction and its poiential use as a natural antioxidant in
protecting and lreating malc reproductive problerns.

Introduction
Honey is a natural product of honey bees and contaiDs moisture and carbohydrares
including sugars such as fiuctose aod glucose. It also contains many other important
components such as proteins including amino acids aDd enzymes, minerals, vitamiN.
phenolic conpounds and organic acids [1,2]. Honey has been repo(ed to have volatiie
substances which are responsible for the characteristic aroma ofhoney
[3].
Scientific studies have showu that honey possesses various imporlant biological
properties such as antimicrobial [4,5], anii-inflarnrnatory
16,71, antioxialant [8,9], anticancer
[10] and imrnunomodulatory properties [i1]. Traditionauy, honey has been used as a
sweetener or food and as a medicine such as for ulcer and wound treatments
[12]. Honey is
also taditionally consumed for enl1ancement of fertility or male reproductive health among

'Tel.: +609-7616 l58i !ax: +609 7653-170i E mail .dd&ss i mahdeem@kcL usm.ny
t32 Mahaneem Mohamed

some populations such as Malays I3l and Indians ll4l. In Malay traditional medicine
practice ofMalaysja, honey is suggested to be taken together lvith other natural pioducts such
as raw egg yolk, pecan and coriander to jmprove sperm production and treat prematrrle
ejaculation U3l. It is also suggested to take honeytogether with raw egg mixed with ginger or
garlic juice before bedtime to increase sexual vnility io South India [14]. In the A)uvedic
branch of treatment called Vajikamna Childtsa (Aphrodisiac Treatment), it is suggested to
take foods such as milk, meat soup and boiled rice along with ghee, oil, meatjuice, sugar and
honey to improve libido [15].

stru€tures and Functions of Male

Reproductive Organs
Iogeneral. normal male fertility depends on normal structure and function of male
reproductive organs including normal levels of reproductive hormones, spermatogenesis,
sexual function to deliver the sperm into female reproductive tract du.ing sexual intercourse
a capability of sperm to fertilize the orum in producing offspring. Based on physiological
functions, the organs can be grouped into 4 $oups which include gonads (iestis), ducts
(epididymis, vas deferens, ejaculatory duct and urethra), accessory sex glands (semioal
vesicles, prostate, and bulbourettral glands) and supporting structures (penis and scrotunr.
The testis involves in the production of sperm or spermatogenesis and production of
reproductive hormones. The ducts transport and storc sperm, and assist in sperm maturation.
Accessory sex glands produce secretiolls that protecl and facilitate sperm movement. The
penis delivers sperm jnto the female reprcductive tract and the scrotum supports the testis
tl6l.
Synlhesis and secretion ofthe important male reproducti\e hormone namely testosterone
is regllated by the hypothalamic-pituitary-gomdal a{is. Briefly, gonadotropir-releasiDg
hormone secreted by hlpothalamus stimulates the secretion of gonadotropins namely
luteinizing hormone and follicle-stimulating hormone. Luteinizing hormone stimulates
secretion of testosterone by Leydig cell while follicle-stimulating hormone and testosterone
synergistically stimulate the secretion of androgen-binding protein by Sertoii cell in the testis.
Androgen-binding protein binds to tesiosterone to keep a high concentration oftestosterofle in
the testis as testosterone stimulates spermatogenesis and rcgulates the secretion of
gonadotropin-releasing hormone and luteinizing hormone. Sertoli cell also secretes inhibin
whish controls the secretion of foll icle-stimulating hormone 6l.

Male Reproductive Health and Honey

Supplementation in Healthy Humans and Animals

Despite all the traditional claims, to date only a fcw studies havc boen reported on the
possible effect ofhoney supplementation on male reproduciive health.
 Hone, and Mcle Reproduc ti\e Health i33

In a study done among 20 healthy human maLes, aged from 25 to 30. oral
supplementation with 20 g honey plus 1280 g propolrs dajty for 2t days does
nor rtier the
level of urinary testosterone compared with baseline value and control subjects
[17].
However, supplementation of 70 g honey suppiemented to healthy cyciists for 8 weeks
significantly reduces semindl inflammatory c),tokines such as interteukin (IL)_18, IL_6, IL_8,
and tumor necrosis factor-o. It also significantly reduces ihe levels ofseminal
oxidative stress
biomarkers such as reactive oxygen species and malonaldehyde as well as increases semjnal
toial antioxidant capaciq, and antioxidant enzymes such as superoxide dismutase and catalase
I8l. In an experimental animat study, daily oral supplementarion of 2 ml honev to male
bonnet monkeys for 30 days significantly increcses snenn count rn semen rlrthout inv eff.ecrs
on the levels of testosterone and gonadonop;ns rs compared urth brseline vclue
[]91.
Furthermore, a sigificantiy higher epididymal sperm count and relalive weight ofepjdid;mis
are also found in adutt healthy rats fbllowing the daily oral supplementation
ofS% palestinran
honey for 20 days as compfied with control rats. The level oftesticular enzrane activity
such
as sorbitol dehydrogenase (involves dudng sex organ maturation) is higher
and the Ievet of
another testicular enzyme activily such as Iactate dehydrogenase (involves durmg
spermatogenesis) is lorver in honey,supplemented group co pared with controjs
[20].
Recently, Malaysian honey at a dose of 1.2 g/kg daily for 4 rveeks also significantly increascs
epidydimal sperm count without affecting spermatid couot anal reproductive hormones which
nuy suggest the spermiogenesis enhancing eflect ofhoney in adult rats
[21]. It is postulated
that the effect of honey on lncrcased sperm count may be due to its constituents
including
antioxidants which can protect against or teduce oxidative damage of germ cells or
speEn
[20,2t1.

Cigarette Smoke, Oxidative Stress and Honey

Supplementation on Male Reproductive Health
The decline in male reproductive health and feftility for the past 30 years has been
liDted
to environmental toxicants 122,231_ One of the toxicants that have beeD reported to have
detrimental effects on IIIale reproductlve health is cigarette smoke (CS). Many stuclies
have
been repo.ted on the detrimental effects olCS on structure and function of male reproductrve
organs in huran and animalmodels.
In human, cigarette smoking has been sho*n to be associated wjth abno.malities in mate
reproductive fluction such as decreased sperm count
[24] and motility [25], increased
percentage of morphologically abDormal sperm
[26], sperm chromatin damage 127, 281,
erectile dystunctior [29] and early pregnancy loss
[30]. In experimenral studiei. decreasea
testosterone level [3 ] l, 1ow sperrn count aid motility
[32], low number ofLeydjg cells 131l as
w€ll as reduced fertitizing potenrial of sperm 1321, embryonic developmint
blastocysi capacity for implantation I34l are found in rodents when exposed to
;3iland
CS.
Although the sxact nechadsm is not clcarly understood, it is postulated tbat
CS induces
oxidative stress causing det menial effects on funciion and structure of Dule reproductive
organs [35,36]. Oxidative stress is a consequerce ftom imbalance between the production
of
reactive oxygen species and ihe antioxidant system in cells Reactive oxyg"n
[37]. speci"s ure
oxygen-containing compounds that are highly reactive free radicals such as hydroxyl
radical,
134 Mahaneem Mohamed

superoxide anion, peroxyl radical and organic rudicals or compounds that are readily
converted to these free radicals such as hydrogen peroxide and hypochlorous acid. Another
group of oxygen-containing radicals js known as reactive nitrogen oxygen species which
contain nitrogen and oxygen such as nltric oxide, nitrogefl dioxide and perox),nitrile. Free
radicals have a single unpaired electron in an orbital and able to exist independently. They are
highly reactive and unstable, which therefore can initiate chain reaction by donating or
accepting an eLecfi'on from other molecule to complete their own orbital and subsequently
achieve a more stable stale. Reactive oxygen species may be generated from oxygen in cells
as products or by-products either non-enzymatically ftom coenzyme Q in mitochondrial
electron transport chain or from metal-containing enzymes such as oxidases and peroxidases
which use oxygen as a substrate. Other soLuces of reactive oxygen species are exposure to
infections, ajr pollutants, ionizing radiation and CS [3 7] .
CS contains more than 4000 compounds and some of them are toxic and carcinogenic
[38]. CS has also been reported to have free radicals such nitric oxide, quinone, semiquinone,
hydroquinone and carbon-cent.ed radicais such as acyl- aDd alkylaminocarbonyi radicals
[39,40]. Nitric oxide can then be oxidized to from nitrogen dioxide while quircne,
semiquinone and hydroquinone can be oxidized to form superoxide anlon which eventuaily
forms hydrogen peroxide and hydroxyl radical [39].
Free radicals can cause cellular dysfunction or damage by reacting with lipids, proteins,
ca$ohydrates and deoxyribonucleic acids. High level of cellular damage can lead to cell
death through apoptosis or rccrosis [41]. The reaction of free radical on lipids results in lipid
peroxidation. For instance, free radical such as hydroxyl radical (as an initiator) extracts a
hydrogen atom, preferably from the double bond of a polpnsatu,ated fatty acid in a
membrane lipjd. With the addition of oxygen, the chain reaction is propagated to form Iipid
peroxyl radicals and lipid peroxides. This resL ts in lipid degradation which forms products
such as malonaldehyde, ethane a.d pentane. Malonaldehyde is widely used as a marker of
lipid peroxidatior by free radicals [37].
Free radicals can also cause damage to protein by modifying the polweptide either on the
peptide backbone, various nucleophilic side chains and redox-sensitile side chains resulting
in formation of protein carbonyls. Protein carbonyl level is used as a marker of oxidative
damage to proteins [4]1. The damage to the peptide backbote is initiated when the free
radical oxidizes the peptide by abstracting ihe hydrogen from the d'carbon in a peptide chain.
This. in tum results in formation of o-carbol1 radical. This o_carbon radical may cross-lin]r
with another o-carbon radicat by radical coupling or may react with oxygel Reaction wilh
oxygen may form peroxide intermediates leading to rcarangement and subsequent clealEge
of the peptide bond to form carbonyl-containing peptides [42]. The oxidized proteins may
ofproiein struchue and function [41].
lead to an alteration
Deoxyribonucleic acid damage by free radicals may results fiom reactions with nucleic
acid bases, deoxyribose residues or the phosphodiester backbone. For example, hydroxyl
radical can cause base alte.ation by adding to double bonds of deoxfibonucieic acid bases
such as adenosine, guaninc and p)T imidine io produce deox)'ribonucleic acid adducts such as
8-oxo-7,8-dihydroxydeoxyadenosine, 8-oxo_7,S-dihydroxyguarosine and p).rimidine glycol,
respectively. It also can abstract hydrogen from the deoxyribose leading to single-st1nd
breaks. Deoxyribonucleic acid damage may trigger si$alling cascades that slow sell cycle
progession or lead to apoptosis. Furthermore, deox)"ribonucleic acid adducts such as 8-oxo-
 Honey and Male Reproductive Health 135

7,8-dihydroxydeoxyadenosine and 8-oxo-7,8-dihydroxyguanosine can induce deoxyribo-

nucleic acid mutation [41].
There are antioxidants to protect the cells against the oxidati\e damage by free radicals.
The antioxidants can be divided into two groups namely enzymatic antioxidants and non-
eruymatic antioxidants. The enzymatic antioxidants are superoxide dismutase, catalase,
glutathione peroxidase, glutathione reductase
[37] a t glurathione-S-transferase [43]. The
non-enzymatic antioxidants are glutathione, vitamin E (o-tocopherol), vitamin C (ascorbic
acid), flavonoids [37] and metal binding proteins such as transferrin and ceruloplasmin
[44].
In general, the enzymatic antioxidants converr rcactive oxygen species or free radicals into
non{oxic products while the non-enzyrnatic antioxidants terminate free radical chain
reactions orpreveflt the fo.mation of free radicals [37].
Superoxide dismutase converts superoxide anion to hydrogen peroxide and oxygen. lt
presents extracellularly or intracellularly in c),toplasm and mitochondria. Hyrlrogen peroxide
can form hydroxyl radical in Fenton or Haber-Weiss reactions. ln Fenton reaction. ;ansiron
metals such as fefious (Fe2*) ancl copper (Cu-t, catalyse formation of hydroxyl radical from
hydrogen peroxide. In Haber-Weiss reaction, hydroget peroxide reacts with superoxide amon
to generate hydroxyl radical. However, catalase, which is present in poroxisomes, may reduce
hydrogen peroxide and subsequently forms water dnd oxygen. In addition, with the presence
of 2 molecules ofreduced glutathione, glutathione peroxidase, which is present in c)loplasm
and mitochondria, may also reduce hydrogeD peroxide to form water and oxidized glutathione
or glutathione disulphide. Oxidized glutathione will then be reduced to form reduced
glulathiore by glutathione reductase, a nicotinamide adenine dinucleotiale phosphate_
dependenl enzyme [37]. Clutathione-S-transferase, another antioxidant etrz],nr that preserts
in cltoplasm and mitochonalria may also play a role in detoxilying process by catalysing the
conjugation of reduced glutathione with various products ofoxidative stress and
xenobiotics. Reduced gluiathione conjugates are then excreted from the ce "teit.op-hilic
[43].
Ciutathione (y-glutamylcysteinylglycine), a trlpeptide composed of glutamate, cystein
(which has sulftydryl group) ard glycine, presents in all tissues especially in liver.
It exists in
two fonff namely reduced glutathione and oxidized glutathione
[45]. Reduced glutathione is
the predominant form and oxidized glutathione content is less than 1% of reduced glutathione
[46]. Aboui 90% ofcellular reduced glutathione js in the c],topIasm, 10% in the mitochondria
[47] and a small percentage in the endoplasmis reticulum [4g]. It acts as antioxidant by
reduction ofhydrogen peroxide in the presence ofglutathione peroxidase. In this process,
it is
oxidized to form oxidized glurarhione and then reduced back ro realuced gl;itathione by
glutathione reductase at the expense of reduced form of nicoiinamide
adeni; dinucleotide
phosphate, forming a redox cycie
[37]. Reduced glutathione can also form conjugate with
various oxidative stress products such as aldehydes, quinones, epoxides, and hydroperoxides
catalyzed by glutathione-S-transferase [43].
Vitamin E such as s-tocopherol is a lipjd-soluble antioxidant that protects against lipid
peroxidation in the cell membranes. It terminates ftee radical chain reaction
by donating an
elecbon to lipid peroxyl radical and subsequently donating another electron to another
ipid
peroxyl radical. These two steps reactions form the more stable lipid peroxides
while vitamrn
E itselfis converted to the fl ly oxialized fonr. Vitamin C such ai ascorbic acid.
on the other
hand, is a water soluble antioxidant and circ[lates Lmbound in blood and extrace]lular
fluid. tt
also can terminate Aee radical chain reaction by donating electrons to free radicals in
two step
r36 Mahaneem Mohamed

reactions and it becomes oxidized. In addition, vitamin C can also regenerate the reduced
form ofvitarnin E by donating electrons in a redox cycle 1371.
Phenolic compounds, namely, flavonoids which are present in plant-derived food have
been hypothesized to act as antioxidants. They may (i) inhibit the enzymes responsible for
superoxide anion lormation such as xanthine oxidase, (ii) chelate ferrous and copper which
may prevent the invohement ofthese metels in the Fenton reaction to form hydroxyl radical,
(iii) donate elechons to superoxide or lipid peroxyi radicals, and form a complex with {ree
radicals to stabilize them [37]. Metal binding proteins such as lransfe[in and ceru]oplasmin
act as antioxidants by ensuring that the metals are nuintained in nonreactive state 1441. The
actions of these enzymatic and non-enz],madc antioxidants on reactive oxygen species are
ilhlstrated in Fieure i.

... I ,6-*6 t

Figurc l. ActioDs ofenzymatic and non-enzlmatic antioxidants on rcnctive oxygen species. Or,
oxyged; SOD, superoxide dismutase; GPx, glutathione peroxidasei H1O, wateri PUFA, polyunsaturated
fatly acid; CAT, catalaseiGSH, glutathione;GSSC, Slutathione disulphide;CR. glutathione redllctase;
ROS. rea.rrve ox)ger .pcci<s. us']. .l'rr,rhione \-u"r'fera e. N {DP . n.co .namrde aden,ne
J D-.leonde phosD r,1re: \ \DPH. reo,'cc,l lom ot NADP

Testicular cells and spemutozoa are susceptible to oxidative damage by free radicals as
their plasma membrane contains abrurdanse of polpnsaturated fatly acids [49]. However,
they are normally protected against oxidative damage by a fiumber ol antioxidanis present in
germ cells, sperm and seminal plasma. In human, superoxide dismutase is present in sperm of
the semen [50], spermatogonia of testis, basal celi and stereocilia of the principal cells of
epidjdymis, epithelia of vas deferens, prostate and seminal vesicles [51]. Furthermore,
catalase is present in human sperm and seminal plasma [52]. Although little is known about
the presence ofother antioxidalts in human sperm and reproductive organs, antioxidants such
as glutathione, superoxide dismutase, glutathione peroxidase, glutathione reductase and
glutathione-S-transferase are found in
intersiitial tissues, Sertoli ceils, pach,'tene
spematocltcs, round spennaiids and epididymal sperm oi rat testis [53]. The other antioxidant
.uch as cd.alase is cl50 rouno in rat le.trs [54].
Moreover, human seminal plasma contains both eM],rnatic and non-enzymatic
artioxidants. The enzlmatic antioxidants arc supsoxide dismutase [55], catalase [52],
glutathione peroxidase [56], glutathlone reductase [57] and glutathione-S{ransferase 1581. It
is suggested that the protective enzymes such as catalase, glutathiore peroxidase and
 Honey and Male Reproducrive Health
t37

glutathione reducrase are contribured largely by prostate

and ]ittle by epididynis [57]. The
non-enzymat;c rnt,ioriLlanls reponed to be pre.enr in hLrl.an
semrnal pla-r" gtrt.,t io*
trdl,-ascororc acrd [)y]. o-rocopherol [60], LLrate [61], coenzyme
"r.
zinc [63].
et0 or ubiquirol
162l dnd
Studies have shown the production of oxidative stress by
CS in the senrrn and testis.
Increased levels of hydrogen peroxides and leukoc),te
otiun u. *.ll
level of total antioxidant capacity are found in semen "on""nt
of infedle .rnot "" ";;;r"O
*itl,
infertile non-smokers and heatthy non-smoker sperm donors
In
"r,
addition, "o_pal"a
[35]. higher ie./el of
8-deoxyguanosine and lower level of a{ocopherol are founj
f\pel]menlal dnimJI .rrdie. aLo show rfp producrion oto\idnli\e
in semen arn*e .;rJ""
iool.
srre.s;ri.r,i. f"i,"i,,"e
exposure to CS. There is a significanrly hjgher malonaldehyde
tevel in rar restis after 45 days
ofexposue to CS as compared to controls. This rs also asiociateLt
with a ,i*r,f,""r,fr'f"*",
level of antioxidants such as glutathione and gturathione peroaidase
actrv,,r]" ."i ,"ri"irUl
Fulhermore, the number ofapoptoric body in rhe rates;is is
atso srgnifi.;r;ir;i;;;;;'h,"h
may suggest that CS induces oxidarive stress leading to apoptosis
in ;at testis iO+]in unotf,".
study, CS exposure for 60 days significantly increases rhe t"*t.
of niti"'o*li""una
malonaldehyde in rat restis. Lower level ofglutathione peroxidase
activiry _-- -
L*1,
in the rat testi. "rJiigf".
of catalase and superoxide dismutase activities are also lound
Honey has been reported to have antioxidants sueh as vitamrns
Gi.
C and E, catalase tl,66l
and phenolic compounds such as flavonoids aod phenolic
acrds [67,68]. f; ,i"; ;;:;rr",
antiradical and antioxidant properties
[9,69,70]. These findings, therefore, hn"" f.J l-rr"."r,
to investigate rhe possible beneficial role of honey supptem-entation ^'"
t, ;;;;;;Jlrl,
reducing the detrinental efiectof CS on nrale reproductive fr.ati ,.i"g-"r"il"a"f. ",
Supplementation of honey (a wild muiriflorat honey from
Malaysi"l ,ig.ti;"iltfy i;.;r",
erectile fundion shown b) improveLl percentages of rats achieviig ;"t."In;r.io'n
_as
cjacruatron ds wer cs sjgnificantry rmpro\es mating and
*a
fertirity indexe;of male rats when
exposed to cs for 13 weeks
[7r]- Improved testicular functions in terms
sperm count, daily sperm prcduction as well as percentages
or,".t*i"."*
i."a,
of motile sperm and
morphologically abnormal sperm are also obsened
1721. Furtherirore, hr.rofo*i"ui'r*a,
'ho$. that hone) supoJemenrarion srgnificantty reduces the roirc etf.., ,.pr"Ai""fro
organs of nrale mts [n rat testis, honey supplementation "laii" ..;;;i.;;",,.
sLgnificanily i.pror.,
tubule drameler and_€pirhetial herght. Leydig cell count
a;d th" ,"i""r"n"
rnoure wrth germ cetl loss [73]. In carLda epididymis, "f.".i"ii"."""
the histological changes are reduced as
the height and nuclear size ofthe epithelial cells are resiored
and ihe numb"i
cells rs lrsqer ln \enlrat pro.rdle. rrre eprrhetial he,8hl ,s "f""f".*J "L*
sigrjlr.anrty,....;:;;;;-i.",
rnterslrlrdl oedenla [74_. In ral tesli.. honei srpplementa(ion
ai\o significantl) reduces lrD,J
peroxialation as well as increases total anrioxidant
sratus. The ;ndoge;"
enzymes such as superoxide dismntase, catalase and glutathjone
;;;,;r,_of.o
pJ.o*ia*"
s:gnificantly resrored in.rhr testis of rats e\posed to CS "."
[7j1. The findi,U ,i""" t"r"r""r
eriecrs or noneJ r. probdbty,hJourh ir. \ariou. ",
con5tituenrj due. ar reasr in parr, to rherr
syneryistic antioxidant properiy to scavenge reactive
oxygen species or c"*,"*"i
stress produced by CS. This wild honey has "*ar,ir"
riro
becn strowo to trave phenolic
antioxidant properries [70]. Therefore, it is possible thar
c;;;;;;;;; r,
this;ntioxidarrp;;;;;
,Tll:f ro ph(ootic compound. or pobpt-cnot. p,."eot in r,on.y ,, ric]lrl
"];"
:.::,1]
srgrrlcanr bel\een rora. phcnolic conrent rnd JItio^rddnt antt antLrajicat
a(uvrues or^corretrtronc
hoDey hale been obsened [69]. Neve(hcless. fir.ther
study is suggested to
138 Mahaneem Mohamed

elucidate the exact molecular mechanism of action ofhoney in counteract,ng oxjdatjve stress-
induced reproductive toxiciry by CS exposure. Apart from supporting the traditional belief,
these experimental studies may also suggest the possible beneficial effecl of honey
supplementation, either alone or in combination with other medications, to protect against or
improve male reproductive problems related to oxidative stress among human when exposed
to CS or other toxicants which also needs further studies.

Conclusion
The beneficial effect of honey supplementation on male reprcductive health has been
shown in a few clinical and experimental studies. Nevertheless, further clinical studies should
be done to explore the potential use of honey supplementation as a naiual antioxjdant in
protecting and treating male reproductive problems related to oxidative stress. Evaluation of
semiml oxidative stress status among males is not routinely practiced although it is suggested
as one ofthe causes of male infertiLity. Therefore, attention should be direcled at producing
simple method to evaluate seminal oxidative stress and its threshold level as \'!ell as at
determining and sta[dardizing the dose and duration of honey supplementation in hul1an
males.

References
tll Board NH. Hdrefr ,4 relercnce flide (20t0 A-pril 8); Available
to Nature's sweetener.
fromr httpr/www.honey.conr/images/dowoloads/refgnide. pdl
t21 Mato, I; Huidobro, JF; Simal-Lozano, Jl Sancho, MT. Significance of nonaromatrc
organic acids in honey. "I Food Pro|.,2003.66(.12),23 7l'23 76.
t3l Perez, RA; Sanchez-Brunete, C; Calvo, RM; Tadeo, JL. Anal)sis of volatiles ftom
Spanish honeys by solid-phase microextmction and gas cfuomatogaphy-mass
spectrometry. L4gric. Fo od C hem. ,2002, 50(9), 2633-263'7 .

l4l Tan, HT; Rahman, RA; Ga[ SH; Halim, AS; Hassan, SA; Sulaiman, SA; et al. The
aniibacterial properties of Mataysian tualang honey againsl wound and entelic
micrcorganisms in comparison to manuta honey. BMC Cot plement Alte Med.,
2009.9r34.
t5l Molan. PC. The Antibacterial Activity of Honey. l. The Nature of the Antibacterial
Activiry. Bee Ilrorld, 1992, 73 , 5 -28
t6l Prakash. A; Medhi, B; A\.'ti, PK; Saikia, UN; Pandhi, P; Khanduja, KL. Effect of
different doses of Manuka honey iD experimentally induced inflammatory bowel
disease in rais. P/]-t rolre,.. Rer., 2008,22( I l), l5l l-1519.
t11 Bilsel, Yi Bugra, D; Yamaner, S; Bulut, T; Cevikbas, U; Turkoglu, U. Could horey
have a place in colitis therapyl Effects of hofley, prealnisolone, and disulfiram on
inflar mtion. niiric oxide, and ftee mdical formation. D€. Sr/g,,2002, 19(4),306-311.
t8l Beftetta, G; Granata, P; Ferrero, M; Orioli, M; Facino, RM. Standardization ol
antioxidant properties of honey by combination of spectrophotometoic/fluoromet.ic
assays and chemomet cs. A al. Chim. Ac1o,2005, 533, 185-191.
 Honey and Male Reproductive Health 139

[9] Perez, E; Rodriguez-Malaver, AJ; Vit, p. Antioxidant capacity ofVenezuelan honey rn

wistarrat homogenates.l Med. Food,2006,9(4\, 510-516.
[10] Swellam, T; Miyanaga, N; Onozawa, M; Hattori, K; Kawai, K; Shimazoi, T: et al.
Antineoplastic activity ofhoney in an experimental bladder cancer implantaiion model:
in vivo and in vitro studies. Int. J. Urol.,2003, 10(.4),213-219.
[11] Tin1m, M; Bartelt, S; Hansen, EW. Immunomodulatory effects of honey cannoi be
distinguished from endotoxin. Crtokine, 2008, 42( I ), I I 3 - I 20.
I12l Bogdanov, S. A Short History of Hor,ey. I The book al honey. Bee Product Science;
[20] I May 15]; Available from: httpi//w\\1v.bee-hexagon.net/fiies/fiie/fileE/Honey
/2HoneyElabomtiorl.pdl
[3] Pengarang, S. Air mani-Memekatkan. Id 190 Kolek:Ji Ubatubatan Traditiondl. Banl
Caves: Education Matters Sdn. Bhd.t 2008t7-8.
ll4l Ttuesiapaulose. Sweeten your Sex y,ith Ho ef.l2009 Nov 231; Available froml
http://socyberty.con/sexualit/sweeten-your-sex-with-honey/.
[15] Ttuesiapaulose. Ten Set Tips on Ayutveda.l2o09 Nov l5l; Available lroml
http i/,/healthmad.conr/alternative/ten-sex{ips-of-a}urveda/-
u6l Tortora, GJ; Derrickson, BH. The Reproductive System.In: Pr.lr.rples ofAnatamy and
Phrsiolog: Maintainunce and Continuity of the Humm B.,.rr. I2th edition. New
wiley and Sons Pte Lid.;2009; l08l-1095.
Jersey: John
l17l Gambelunghe, C; Rossi, R; Sommavilla, M; Ferranti, C; Rossi, R; Ciculi, C; et al.
Effecls of chrysin on urinary testosterone levels in human males. I Med. Food,2003,
6(4),387-390.
l8l Tartibian, B; Hajizadeh Maleki, B; Abbasi, A. The effects ofhoney supplementation on
seminal plasma cltokires, oxidative stress biomarkeN, ard anti-oxid rts durirg 8
weeks ofintensive cyclingljaining J. A dtol,Dd: l0.2l644androl.ll0.0128l5.
ligl Gill-Sharma, MK; D'Souza, S; Parte, P;Balasinor, N; Choudhuri, J; Majramkar, DDi et
al. Effect oforal tamoxilen on semen characteristics and serum hormone profile rn male
bomet monkeys. Corrdception. 2003, 6'7 15\, 409-113.
[20] Abdul-Ghani, AS; Dabdoub, N; Muhammad, R; Abdul-Chad, R; Qazzaz, M. Effect of
Palestinian honey on spermatogenesis in rats.l Med. Food,2008, ll(4),199-802.
l21l Mohamed, M; Sulaiman, SA; Jaafar, H; Sirajudeen, KN. Effect of different doses of
Malaysian honey on reproductive parameterc in adult male rats. Andrclogia. Doi:
10.1 1 I 1t.1439-0272.2010.01 159.x.
[22] Sikka, SC; Wang, R. Endocrine disruptors and estrogenic eflects on male reproducti\e
a"\is. Asian J. Androl.,2008. l0(l), 134-145.
[23] Saradha, B; Mathur, PP. Effect of environmental contaminats on male reproduction.
E v iron. Tor i.ol. P hatnaco 1.. 2006. 21, 34-41.
I24l Richthofl J;Elzanaty, S; Rylander, L;Hagmar, L; Gi\\ercman, A. Association between
tobaooo exposure and reproductive pammeters in adolescent males. Inl. J. Andrcl.,
2008,3r(l).3r-39.
[25] Gaur, DS; Talekar, M; Pathak, \?. Effect of cigarette smoking on semen quality of
infefiile men. .tirgdpo,"e Med. J. ,200? , 481.2), 1 19 -123 .
[26] Evans. HJ; Fletcher, J; Toffarce, M; Hargeave, TB. Sperm abnormalities and cigarette
smoking. Zdncel. 1981, I 18221), 627 -629.
[27] Potts, zu; Newbury, CJ; Srdth, G; Notarianni, LJ; Jefferies, TM. Sperm chomatin
damage associated with male smoking. Mrldt Rer., 1999, 423(l-2), 103-l I L
140 Mahaneem Mohamed

[28] Sepaniak, S; Forges, T; Gerard, H; Foliguet, B; Bene, MC; Monnier-Barbarino, P- The

influence of cigarette smoking on human spem quality and DNA fiagmentation.
Tot ic a 1o ey, 2006, 223(1 -2), 5 4-60.
[29] Shni, R; Koskimaki, Jt Hakama, M; Hakldnen, J; Huhtala, H; Tarnmela, TL; et al-
Effect oflife-style factors on iocidence oferectile dysfunction. /rt. L,ipor nes.,2004,
16(s),389-94.
I30l Venners, SA; Wang, X; Chen, C;Wang, Lt Chen, D; Guang, W; et al. Paternal smoking
and pregnancy loss: a prospective study using a biomarker of pregnancy. lrn. -.
Ep ideniol., 2004. 159(10), 993-1001.
[31] Yardimci, S; Atan, A; Delibasi, T; Sunguroglu, K; Guven, MC. Long{erm effech of
cigarette-smoke exposure on plasma testosterone, luteinizing hormone and follicle-
stimulating hormone levels in rnale rats. ,B/. I Urol. , 199'7 , 19(l), 66-69 .
[32] Yanamoto, Y; Isoyama, E; SoJikitis, N; Miyagar?, I. Effecis of smoking on testicular
function and fertilizing polential in rats. U,"ol. Rer., 1998, 26(l), 45-48.
[33] Polyzos, A; Schmid, TE; Pina-Guzman, B; Quinlanilla-Vega, B; Marchetti, F.
Differential sensitivity ofmale germ cells to mainstream and sidestream tobacco smoke
in ihe mouse. Toricol. Appl. Phamacor, 2009, 23 7(3 ), 298-3 05.
[34] Kapawa, A; Giannakis, D; Tsoukanelis, Ki Kanakas, N; Baltogiannis, D; Agapitos, E:
et al. Effects of patemal cigarette smoking on testicular function, sperm fertilizirg
capacity, embryonic development, and blastocyst capacity for implantation in rats.
A dtologio,2004,36(2\, 5 7 -68.

[35] Saleh, R-A; Agarwal, A: Sharma, RK; Nelson, DR; Thomas, AJ; lr. Effect of cignette
smoking on levels of seminal ox;dative stress in infertile men: a prospectlve study.
Fenil. Steril.,2002,18(3), 49 t -499.
[36] Rajpurkar, A; Dhabuwala, CB; Jiaq, Y; Li, H. Chronic clgarette smoking induces an
oxidantantioxidant imbalance in the testis. I Envircn. Pathol. ToxicaL. Oncol.2000.
l9(4),369-3?3.
[37] Smith, C; Marks, AD; Liebermann, ML. Oxygen ioxicity and free radical injury. In:
Mdrk's Bo.sic Medicol Biochetnbtl: A clinical appraach. 2nd edition, Maryland:
LippincottWilliams andWilkins; 2005t 439-457.
[38] Nelson, E. The miseries ofpassive smoking. Hum. Exp. Toxicol.,2001,20(2),61-E3.
[39] Church, DF: Pryor, WA. Free-radical chemistry ofcigarette smoke aDd its toxicological
implicatLons. Ediran. Heolth Pe$pect. , 1985 , 64, | | | - 126 .
[40] Bartalis, J; Zhao, 1'l-t Flora, JW: Paine, JB; Wooten, JB. Carbon-centered radicals in
ciga.ette smoker acyl and alkylaninocarbonyl radicals. Anal. Chen.,2009,8112), 631-
641.
I41l Marne$, U; RiggirN, JN; West, JD. Endogenous generation of reactive oxidants and
electrophiles and their reactiorls with DNA and protein. J. Clin.l vejr, 2003, 111(5),
583-593.
[42] Dean, RT; Fu, S; Stocker, R; Davies, MJ. Biochemisiry and pathology of radical-
mediated protein oxidation. Biachetn. J., 1997,324(.1), 1-18.
[43] Hayes, JD; Flanagan, ru; Jowsey, lR. Glutathione transferases.lri,u. Rev Phormocol.
Ioxrcol. 2005, 45, 5l-88.
[44] Halliwell, B; Gutteridge, JM. The anlioxidants of hunan extraccllular fluids. lrcr.
Bioche . Biophls., 1990,280(1), 1-8.
 Honey and Male Reproductive Health t4l

[45] Kaplowitz, N; Aw, TY; Ookitens, M. The regularion ofhepalic glutathion.'. Ann1.t. Re\)_
Phahndcol Tarica1., 1985,25,'7 t'-i 44.
[46] Akerboom, TPt Bilzer, M; Sies, H. The retaiionship of biliary gluraihione disulfide
efflux and intracellular glutathjone disulfide content in perfusecl rat h\et. J. Biol.
C hel1., 1982, 251 (8\, 4248-4252.
[47] Meredith, MJ;Reed, DJ. Status ofrhe mjrochondnrl pool otgt iathione in rhe isotared

[48] Hwang, Ci Sinskey, AJ; Lodish HF. Oxi{tized redox state of glurathione in the
endoplasmic rcticulum.
^tcience, 1992, 257 (5O t 6), t4g6- t SO2.
[49] Alvarez, JG; Storey, BT. Differential incorporarion of l'atty aci{ls into and peroxidative
loss of fatty acids from phospholipids of human spennatozoa. Mol_ Reprod. Dev.,1995,
42(3), 334-346.
[50] Peeker, R; Abramsson, L; Marklund, SL. Superoxide dismutase jsoenzymes in human
seminal plasma and spermatozoa. Mot. Hun. Replod., 1997. 12f3). l06t_t 066.
[51] Nonogaki, T; Noda, Y; Narimoto, K: Shrotanr. Mi Mori. Tl Matsuda. T; er al.
Localization of CMn-superoxide dismutase in the human male genital organs. llrn.
Reprod., 1992, 7 (1\, 8t -8s.
[52] Jeulin, C; Soufir, JC; Weber, p; Laval-Martin, D; Caiva)rac, R. Caralase activiry in
human spermarozoa and seminat plasma. Gd,?ete Rer., I989.24a2). 185_196.
[53] Bauche, F; Fouchard, MH; Jegou, B. Anhoxidanj sysrem rD rat tesricutar cels FrB,!
L e u., 1994, 349 (3\, 392-39 6.

[54] Ben Abdallah, Ft Dammak, I; Mallek, Z; Attia, H; Henrati, B; Ammar-Keskes. L_

Eftects of date seed o11 on testiculdr antjo\idant eMynes and epididlmal sperm
characteristics in male mice. Andtutogia. 2009, 4t (4), 229-234.
[55] Alvarez, JG; Touchstone, JC; Blasco, Lt Storey, BT. Spontaneous lipid peroxidation
and production of hydrogen peroxide aDd superoxide in human spermatozoa.
Superoxide disDutase as major enzyme protectant against oxygen toxiciti. J Androl.,
1987, 8(s),338-348.
[56] ciannattasio, A; De Rosa, M; Smemglia, R; Zaffilli, S; Cimmino. At Di Rosario_ B: er
al. Cluralhione peroriddse rCpX' ajl.! ) in semrDdl pJrsma ot hmlrh\ and inteaile
male.. J. Endo, rinot 1r,Ar. 2002.25tt tl 08l-o8b
[57] Yeung, CH; Cooper, TGt De ce],rer, M; De Ge],rer, C; Rolf, C; Kamischke, A. et al.
Studies on the o.igin of redox enzymes in seminal plasma and their relationship
with
results olin-vitro lertilizatia1. Mol. Hum. Reprad., 1998,4(9). 835_839.
l5El Raijmakers, MT; Roelofs, HM; Steegers, EA; Steegers-Theunissen, RR; Mulder. Tpl
Knapen, MF; et al. GlutathioDe and glutathione S_transferases Al_1 and pl-t
m
seminal plasma nray play a role in protecting against oxidative damage to spennatozoa.
Fefi it. Steril., 2003,'t9(t), t69_t,t 2.
[59] Colagar, AH: Marzony, ET. Ascorbic Acid in human seminal plasmai determinatron
and its relationship to sperm quality.l Ctlin. _Bioc hen. Nu,.,2OO9, 45(2), 144_149.
[60] Fraga, CG; Motchnik, pA; WFobek, AJ; Rempet, DM; Ames, BN. Smoking and low
antioxidant levels increase oridative damage to sperm DNA. M ral. Rer.
, I99;, 3 5 1 (2),
199-203.
161l Thiele, U; Friesleben, HJ; Fuchs, J; Ochsendorf, FR. Ascorbic acid and urate in human
seminal plasma: determination and intenelationships with chemiluniDescence ln
washed semen. I1ulr,. Rep,.od, 1995, l0(l), 110-115.
142 Mahaneem Mohamed

[62] Mdncini, A; De Marinis, L; Oradei, A; Hallgass, ME; Conte, G; Pozza, D; et al.

Coenzl,ne Qi() concentrations in normal and pathological human seminal fluid. I
Andro l., 1994, ls(6), s9 l-594.
[63] Colagar, AH; Marzony, ET; Chaichi, MJ. Zinc levels in seminal plasma are associated
with sperm quality in feftile and infertile men. r'r'uh Res.,2009,29(2),82-88.
[64] Rajpurkar, A; Jiang, Y; Dhabux,ala, CB; Dunbar, JC; Li, H. Cigarette smoking induces
apoptosis in rat testis.l rnircn. Pathol. Toxicol. Oncal,2002,2l{3),243-248.
[65] Oz],urt, H; Pekmez, H; Parlaktas, BS; Kus, I; Oz],tlrt, B; Sarsilmaz, M. Oxidative stress
in testicular tissues of rats exposed to cigarette smoke and protective effects of cafferc
acid phenethyl ester.,rrian J. Androl., 2006, 8(2\, 189-193.
[66] Al-\vaili, NS. Eft'ects ofdaily consumption ofhoney solution on hematological indices
and blood levels ofminerals and enzymes in normal individuals.l Med. Food,2003,
6(2), 13s-140.
[67] Cheldof, N; Wang, XH; Engeseth, NJ. Identification and quantifigation of antioxidant
componerts ofhoneys from various floral sources. J. Agnc. Food Chem.,2002, 50(21),
5870-5877.
168l Yao, L; Jiang, Y; D'Arcy, B; Singanusong, R; Datta, N; Caffin, N; et al. QMntitative
high-performance liquid chromatography analyses of flavonoids in Australian
Eucallptus honeys. I lgl k:. Food Chetn. , 2004, 52(2), 210-2t4.
[69] Beretta, G; Granata, P; Fenero, M; Oriolim M: Facino, RM. Standardization of
antioxidant properties of honey by combination of specirophotometric/fluorometric
assays and chemometrics. AnaL Chim. Acta,2AA5,533, 185-191.
[70] Mohamed, M; Sirajudeen, KNS; Swamy, M; Yaacob. NS: Sulaiman, SA. StLdies on the
aniioxidant properties oftualang honey of Mala,s ia.. A,tt. J. Trud. CA M.2010,1(l), 59-
63.
[71] Mohamed, M; Sulaiman, SAi Jaafar, H; Sirajudeeo, KNS. Effects of Malaysian
Tualang honey on reproductive hormones, sexual behaviour and ferlility in male rats
exposed to cigarette smoke. J. ApiPtod. ApiMed. Sci.,2010,2(l),54.
[72] Mahaneem, M; Sulaiman, SA; Jaafar, H; Sirajudee\ KNS. Effect of honey on testicular
functions in rats exposed to cigaretle smoke. LlpiProd. ApiMed. Scr., 2011, 3(1), 12-
t"/.
[73] Mohamed, M; Sulaiman, SA; Jaafar, H; Sirajudeen, KNS. Eflects of Malaysian
Tualang honey on oxidative slress markers and testicular histology in rats exposed to
,
cigarctte smoke. lpiPlod. ,4piMed. Sci.,2010,2(1),54.
[74] Mohamed, M; Sulaiman, SA; Jaafar, H; Sirajudeen, KNS. Histological changes in male
accessory reproductive organs in rats exposed to cigarette smoke and the proiective
effect ofhorey supplementatlon. J. ApiPrcd. ApiMed. Scr:, 2010, 2(l), 55-
 
 
  

 
  

View publication stats