ON TESTIS AND EPlDlDYMlS OF RATS - Pondicherry University ...

ioavaiiability andlor production of testosterone
and also thc cstrogfnic and antiandrogenic activitics
of thc mcthoxychlor and its metabolits.
Thc rncchiinisn~ of mclhoxychlor mcdialod 0x1-
ililllvc strcss is not "cry clcar but ~t has bocn
shown lo bc mcdiatcd by thc activation of microsome-nch
monooxygenax, which a involved ~n
the convcrsnon of methoxychior Into its reacttve
mctabolitcs (Bulger el ai.. 1983). During this reaclloll
tllc ~cibctlvc 1I1~l.lb0lilCs. possibly free ~di.
cals. b~nd wvaicntly to microsome-rich
components (Bulger et al . 1983). 11 has been
shown that human cytochrome P450 enzymes.
rcsponslblc for tlic conversion of mothoxychlor
lnto 11s major mclaboitler and CYPIAZ, havc
been shown to play e predommilnt role in'thir
reaclloii (Slrcsscr and Kupfer, 1998). The ablilty
of cytoclirome P-450 system lo lnduce ROS has
been wcll documented (Bondy and Naderi. 1994)
It has bcco reported that ROS such as H,O,
appcdrs lo be a key agent In the cytotoxtc erects
In alxrn?.\tozo;t iwd 111 itddltlo!, to thew dlrcot
cffcct on ccllulnr constituent produce oxcdatlve
stress by dccreas~ng the enzymatic defenses of the
tcais (Grlv~au and Lannou. 1997). In the present
nudy. ad~nlnlstration of mcthoxychlor dccrcased
thc i~cliv~t~cs of ~ttulurc, superox~dc d~smutnrc.
piutathionc reductax, and glulathtonc peroxidase
and concomitant incrcaw In the levels of H?0,
and hpld pcroxldal~on dificrentiaily in the mltochondrral
and msrosomc-rich fractions of rat
tcrtls Thc marlmum decllnc In the actlvltlcs of
ontioxId.tnl cnrynlcs was obscrvcd In mlcrosomc
rlch fracuans followcd by mltachondrtal fractions
aftcr mcthoxychlor trcntment. Superoxlde d~smutarc
1s conskdercd the first llne of defence against
delcter~aus cKec(s of oxyradicais In cell by catalyz~ng
the d~rmutat!on of superoxidc rad~cals to
H,02 and molecular oxygen. The rcduct~on in the
ncttvaty of catalar may rcflect ~nabilzty of tesllculilr
m~tochondrta and mscrosomes to cl~mtnatc
11,0, produccd by thc actwellon of mcthoxychlor
and 11s n~elabol~ler. Th~s may also be due to
cnzyme ~naclbvation cawed by taws ROS production
in mttochondr~s and mtcrosomes (Pigco-
Icl et "1.. Il99U). Thc nnt~oridant cnrymcs cnlnlusc
and pcroxtdarc protect superoxide dismutasc
against mactlvatlon by H,O,. Rcc~procally, the
superoxide d~smutase protects the catalase and
peroxidase against inhibition by superoxtdc anion.
Thus. the balance of this enzyme system may be
crscntlal to gct rid oTsuperoxidc anion and pcror.
ides generated in subaeliular companmmts of the
testis. The reduction in the activities of anttoxldant
enzymes and increase in H,O, and lipld
peroxidation wuld reflcct the adverse effect of
mcthoxychior on the antioxidant system in testis
suhccllular fruchons. The ROS cause damage to
m~lochondr~al and other cytoplasmic organelle
membrane structures through peroxldatlon of
phospholipids, proteins and nucleotides. Undcr
hlgh ROS concentrations prc-damaged spermalolo*
arc exposed to hpid peroxldatlon by polyunsaturated
fatty acids (ichikawa el a].. 1999) The
milochondrial and m!crosome-rich membranes
havc been reported to undergo permeabllily
changes following enhanced lip~d peroxidation
and giutath~onc dcplction (Chance et al., 1979).
The results suggested that the low to medium
dnscs exposure or pubcrtal rat lo mcthoxychlor
~nducen dcpletlon in antioxidant defcncc systems
diflerentially in milochandrial and microsome.
rich rracllons ind~cating melhaxychlor-lnduced
ox~daltve stress tn tcrtis rubcellular fractions. Thls
crrcct may lead to dtsruplion In functtonal integrity
of cell organelles in testis and thus the
advcrsc effcct of methoxychlor on male rcproduction
of rats may be due to the induction of
oridanve stress in testls.
The authors acknowledge Dr Ute Ticmann,
Research lnslrtutc for the Biology of Farm Anl.
rnuir. Dummerstorf, Germany for the generous
gait of mclhoxychlor and the staff of the Biolnfor
matlcs Center. Pondcherry University for various
facillt~es C. Latchoumycandane acknowledgcs the
Indian Council of Medical Research, New Delhi
for Scnior Research Fellowship and P.P. Mathur
acknowlcdgcs the Population Council. Ncw York
for financial assistance (Grant Nos.B99.047P-91
lCMC and B99.048RilCMC).