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

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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 <strong>University</strong> 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).
Uc,#!dy. SC. N;tdcru. S , 1% Conlrbbulton or hcpatic cy. lmhrome P4Se ryncml lo the genenuan or rractire oiy. yrn rmia U~~hsm Phsrmncol 48, 155-159 nucpe. J.A . Aun. S D.. 1976 baopmildul utalyd hpd vrox8drunn or mcro.omc-rrh and arllrrul mmbrsnu Btoch~m Unphys As" 444. 192-201 BuIsr, W R . Kuprur. D., 1989 Chsmlcrisl~a ormonwxy. maw-mcdtulcd coraknl btndintl or mthoiyshlor ~n hu. man and rat lrver mict~~)m Drug Meub mul. 17. 487-4'44 Uulger, W 11 . ~ucc.cltclii. R M , Kuprcr. D. 1978. stud,- on [he m vwo ud in uuta -n n~ochcm Phumaeol 27. 1417 24212421 IUIW:, w II . TC~P~~, J.E. KuP~c.. D. 1983 c.,".knt band- 1"s orII4CI melhvxythlor rnclrbollldll LO rut l8v.r mrro. wme.nch Eomponcnu Toitcol. Appl. Phann.sol MI. 367-374 Grlki~. I. Msnncrr,k. 8 . 197s Pvrbrwtnon and ch.r.clm moon d Ihr llrrom- gluolhtom mJucwc lrom r.c llvcr I Btol Chsm 2%. Y74-5.480 Cnrlvn 6. Gnrcrrmm. A, Kcdmg, N.. Stnkkrback. N E . IW1 Er,ckolci r, dccrcannp quall~y olrmcn during DYI~ Yl ywn Ur Mcd J HIS. UN-613 Chuncc, 8. St*. 11. Bovcn%. A . 1979 Ilydropro.~& maabltm tn msmmsl~an arpnr. Phystol Rev 59. 327- SY Ch.l~~n. R B. IIrrris. M W.. Dnrts. B J . Ward. S M . Wtbon. R 8. Mrunuy. M A. Lockh.tn. A C. Smi~lowsa. R J . M'ncr. v C , tlurkr. L T . Collnnr B J . I997 N eneu or pcnndtr1t)urrn~k mdhokychbr sxpaurr m adult mt ~CIIOYT. ammum, ~ n rrprodusu~ d synrm runstson FU". dam Appl Tax& 40. 138-151. Chm. S E . mm hdosnn d"ruplon and mak mproduetlrr runslnon-a Ihon rrvrw In, J Andml 23. 45-16 Chllm. KC . Sujalha. R . LL~h~urny~~dane. C.. Malhur. f P . 2001 EITca or t~ndmc an anuoxhnt auyw m cWsdym8r and rprl,dym;ll rrrrm or adult n~ Auan J A"'J,"l 3. 20s-2M Clalbm. A,. I985 Olrluc In Grrmwuld. R IEd 1, Hmd. bod al Methd lor Oxysn Rsdrrl Raurch CRC P-. Nn York on 283-284 - or mthorychlor an w antuoi~danl or Ganmdhann. 8. ~ i i p n M . A.. Malhur. P.P. ml. Ell- 8-1 @. dzdyd spcm an rolm. Aum J. Andrd. 3. 28l-UII Grry. B L Jr. htby. J . Fcmll. J . Rlhnbrr~ G.. link. R . Cmpr, R . OoMmao. 1.. Slatt. V., bsby, 1919 A bormpmr ansly*. or nrtho~ychla.~dupdm-8 ol rrorodunar dwdmnml and rwuion ia the nt Fun. &m Ap@ Toxrol' 12.91- 108. Cny. L E Jr.Oltby. J . Coopt. R L. Kda. W.R.. 1999 The ntrosnr and .nbsndropn~ mu& meIhox)Ehlor .Ilm the rmroductl*. lncl ."d boh.*ia vilbou, .Irm,n. plunary ua or LA ad preb~in -a m nr* rmi To%rol. Ind llssllh IS. 31-47. Onreau. J F. bnnou. D.L. I597 Rwlin oxy~m awls and human mnnamzoa: phpiobw and pathophyazoloay. Ink. J Androl M. 61-69. Ichikawa. T. Ma, T., Ohmoti. H., Sshill, W 8.. 1999 Rcue llvc oiypn ~mla mnurnc. me asrolome rusttoo bul no1 .crostn sstivily in human ~pnnnlozoe Inl J Androl 22. 11-49 >, -- Knmalh. S A. Namyan, K A . 1912. Interution orUZ- ~nth cndoplatmc rrUEulum of nl llnr Aul Bloshsm. 48. S3-61. Klmcrclicr. G R. Heu. R.A.. 1H8. Tomsology or thr mk crcvrrrnl ducts and a-arl wr plandl In Kcnncch, S K (Ed ). Rcpmlulivc and Dcrclopmml.1 Toricolo8y, m ss3-Is9 hruonlr. A.. Mrmuc~ N. Pou.da. Y. Puo. D.. ~~pu~fina. A I. 2mo ~osmbk C(BLILM andlor antundropnlc .rrrrtr or m c ~ h u i on ~ h prvl*cL~n ~ ~ ~ mkaw ~n ,,,lr Arch Toxrol 74. 170.175 hbhoumy~d~nc. C . Ch81m. KC . Ma~hur. P P . m2r Thc rrrel or 2.3.7.8-lct~chlorndibbbb~pd.dox~~ on the mitoshondrul and micraome.nch rncaa~ or rat lesur Tollsology 171, 127- 13s blrhoum~undane. C. Chxtr.. KC.. Mllhur. P.P. 2002b Thc siT-l of mlhox).chlar on Ihc rpd1dym.1 anl~oiid~nt $)-am or adult n! Rcprod Tax~col I6 #n p m Lutchuumycand~nc. C , Chlln. KC , Malhur, P P , 2m2c lndv~tlon oroi6d.lcvc st- tn tk epldldym.1 lprm or rnl aRcr cipmurr to 1.3.7.8.lclnshlomdlbebe1l).pd&o~.dn Arch TOXISOI in p- Msnor. SC. McDonnel. D. Omdo. K W.. 1998 lnhtb81non or androp rraplardcpdml Innrrlpllonsl .airily by DDT Ismcn snd mlhoxyrhlor In He62 human hcpatom. EEIIS Tnxd Awl Ph.mucol 151. 115-142 Marklund. S . Marklund. G , 1974 Inrolvcmmt or rupraxdc m8an rmdjUI ~n .utoaxhtion or pyraglllol snd a ronw nlnl .%my lor wproild. dmmullw. Eur J Bloshm 47. 469-474 - Mllhur. P P. Chatloywdhyay, S. 1982, lnv~lvrmnl or 1 ~ . .anal mzyma ~n Rutarnidc-nndd stmuhtlon ~n ~ntts Andmlog. 14. 171.176, ~shm-6, F R. 1999. Inrosuons ~n the mk rrnla.l and rucur oxypn Hum. Rcpod Updal. 5. rm..," >, --- Paplm. D E . V.kntinc, W N . 1%7 Sludm on qmntc~tw md qmllutirr ~b~en~llbm dCIYUlm duuthim rnroxd.r J Lab Clmn Mcd 70. 158-I69 pd[&, V , Mmbly., e.. liuhumm. I. Ahotup. M.. 1994 r& ~ - ~ d IS, r d 3;3-&1, . . Pod. E.. K-n. Y. 1911 Supraild. anoat and H,D, produclia by chmiully elmled pn'laml -ophy..$ndun& bu multiDk nonoh.lonlk slimuli Ccll lmmunol 9. WI-II~ ' ' - ' had.,. E.. Co-, P. Houbnon. A. hbn. D. MA&. D.C. Ra. M.. 2ub.v. D. Ram&. I. I9W
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FUNCTIONAL STUDIES ON THE EFFECTS O
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ACKNOWLEDGEMENTS I wish to express
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TABLE OF CONTENTS Page No ACKNOWLED
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TABLE OF CONTENTS (Continued) Deter
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TABLE OF CONTENTS (Continued) Effec
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TAULIC OF CON'I'ISN'I'S (C'untinued
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xi LIST OF TABLES (Continued) I'agc
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Table 24a Table 24b Table 24c Table
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Fig. 1 Fig. 2 Effect of TCDD on the
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Fig. 12c Fig. 12d Fig. 13 Fig. 14a
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LIST OF FIGURES (Continued) Fig. 23
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LH M PL mg mRNA N AD NADH NADP NADP
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layers, an outer layer of visceral
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tubular epithelium and continually
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lmn~unization of monkeys against FS
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and this reaction is catalyzed by t
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extratubular environment or synthes
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the most active in protein secretio
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1958). A rapid fall in serum testos
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have also been reported in the rats
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Effect of TCDD on heart muscle has
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1.4 Effect of oxidative stress on m
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2 SCOPE OF THE PRESENT STUDY There
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3 MATERIALS AND METHODS 3.1 Animals
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Subgroup III: Administration of TCD
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choppcd with the help of sharp razo
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anti-FSH antibody. After incubation
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lust sped (500 to 700 rpm) on an or
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3.13.4 Quantitative determinntiun u
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The plates were dried by inverting
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centrifuged at 3,500 g for I5 min o
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3.17 Preparation of tiasue humogena
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supcrnutant was taken. Hlunk was pr
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3.21.4 Assay of glutathione peroxid
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4 RESULTS 4.1 Administration of TCD
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seminiferous tubules was found to b
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fractions of rat testis as compared
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4.1.11.1 Effect of TCDD on the prod
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4.2 Co-administration of TCDD and v
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4.2.8 Effect of co-administration o
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4.2.11.5 Effect of co-administratio
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Table I b. Effect of TCDD on the we
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Table 4. Effect of TCDD on the seru
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Table 7b. Effect of TCDD on the pro
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Table 8c. Effect of TCDD on the lev
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Table 9d. Effect of TCDD on the act
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Table 13. Effect of TCDD on the ant
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Table 15. Effect of TCDD on the lev
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Table 16c. Effcct of TCDD on the an
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Table 18a. Effect of co-administrat
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Table 21. Effect of co-administrati
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Table 24b. Effect of co-administrat
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Table 25c. Effect of co-administrat
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Table 26d. Effect of co-administrat
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Table 30. Effect of co-administrati
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Table 32. Effect of caadrninistrati
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Table 33c. Effcct of co-administrut
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5 DISCUSSION 5.1 Significance of th
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Measurement of weights of the acces
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compartment of the cells (Chainy el
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the reduction in daily sperm produc
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eported in the TCDD-treated rats (M
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lilnction is to ililcrccpt lipid pc
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in the animals administered with TC
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protective effects on serum testost
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suygcstccl that vivamin 1: conld im
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Fig.4~. ENect of TCDD or TCDD and v
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tE W d In w it I I (,OCX) 3s PUB (,
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Fig. 7c. Effect of TCDD or TCDD and
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u 3 f ~ = m w * N O .- ~Slew aew en
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Fig.lOb. ENmt of TCDD or TCDD and v
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Fig. 1Ir Effect of TCDD or TCDD md
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Fig. 14c. Effect of TCDD or TCDD an
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Fig. 16b. Effect of TCDD or TCDD an
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Fig.18~. EKect of TCDD or TCDD and
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1 1.2 l4 Fig. 19b. ENect of TCDD or
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Fig. ZOb. Elkt of TCDD or TCDD and
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Fig. 21. Effect olTCDD or TCDD and
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Fig. 22c. Effect of TCDD or TCDD an
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Fig. 24b. Eflect ofTCDD or TCDD and
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7 REFERENCES Aitken RJ, Irvine DS,
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Chitm KC, Latchoumycandanc,C, Mathu
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Flsher JS, Turner KJ, Brown D, Shar
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Hornsby PJ. Regulation of cytochrom
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Latcboumycandane C, Chitra KC, Math
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Moore RW, Panona JA, Bookstaff RC,
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Rommerts FFG, Cooke BA, Van Der Kem
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Slaunwhite WR, Burgett MJ. h virro
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1.1 Preparation of dosing solution
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1.4.6 Wash concentrate One bottle,
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1.7.3 Estradiol controls Two vials.
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1.1 1.2 Orcinol(6%) 6 g of orcinol
Page 201 and 202: 1.16.2 Horseradish peroxidase (8 Un
Page 203 and 204: 1.20 Superoxide dismutase 1.20.1 Tr
Page 205 and 206: 1.24.2 Thiobarbituric acid (TBA; 0.
Page 207 and 208: Chronic effect: of enclosulfan on t
Page 209: enbw1h1.W mu IUY Wcab unpiliml~t at
Page 212 and 213: cbniuis 11~11 b"nci:~lc ~wlive oxyg
Page 214 and 215: DNA, RNA ;uxl Wcin wcrr abarval, wh
Page 216 and 217: Mt~~m(10-lZsu&)vacob- Wfmn Ihehml ~
Page 218 and 219: New Delhi, llrliil Ib SCI~KK Rcm& M
Page 220 and 221: tiii~lc rcprmluction or rut (Cllitr
Page 222 and 223: wciglit (b.wt.) per day for 45 days
Page 224 and 225: 0.1 00 01 " 0.8 I . .lo Dl* rcnn IW
Page 226 and 227: Chilr:~. K.C.. L!olnn!myci!~dum. C.
Page 228 and 229: C. hteboumyeradlos . KC. CMtn . P.P
Page 230 and 231: I. 1 Ilal 01 2 1.7 # I c I ~ ~ L I
Page 232 and 233: Fin. L Corrclatwn bclwfcn "perm cou
Page 235: Iionshii nepmdvctivc mxicity ad upt
Page 240 and 241: o. Glutathione reductage mg pmWn mg
Page 242 and 243: IOWAME -. Tor. #558517 PME: 9 SESS:
Page 244 and 245: JOBNAME: Rqm. Tm. M5W7 PAOB: 11 SBS
Page 246 and 247: t 02 ELSEVIER Toricology OM) (2W1)
Page 248 and 249: ---- - wcre obtu~ncd from E-Monk. G
Page 250: 3.2. A,III~AILNI syrlo~t of ,nIroch
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