Protective Effect of L-Carnitine against Deltamethrin Induced Male Reproductive Toxicity in Adult Rats Exposed at their Prepubertal Stage
DOI:
https://doi.org/10.18311/ti/2023/v30i3/32261Keywords:
Deltamethrin, L Carnitine, Prepubertal Rats, Reproductive ToxicityAbstract
The present study aims to investigate the protective role of L-Carnitine (LC) against Deltamethrin-induced testicular toxicity in male rats exposed during their early developmental period. DTM was administered at a dose of 6 mg/kg body weight to the prepubertal rat’s Post-Natal Day (PND) 23 rats through oral route and exposure was continued until they reach PND 90. After completion of the exposure period, male rats were assessed for reproductive endpoints. Deltamethrin exposure caused a significant reduction in testosterone production and decreased the sperm parameters such as sperm count, sperm motility, sperm viability and sperm membrane integrity. Deltamethrin intoxication also reduced the reproductive organs’ weight and testicular steroidogenic enzymes (3β-hydroxysteriod dehydrogenase and 17β-hydroxysteriod dehydrogenase) levels. Further DTM exposure induced the oxidative stress as evidenced by the significant reduction in the superoxide dismutase, catalase, and glutathione levels with significant elevation in the malondialdehyde. DTM also induced the significant sperm DNA damage. In addition, DTM exposure significantly declined the testosterone levels over the control group, indicating the impaired steroidogenesis. In addition to the compromised steroidogenesis DTM exposure also deteriorated the testicular architecture according to the histological observations. On the other hand, therapy with LC (100 mg/kg body weight) improved the biomass of reproductive organs, the features of the sperm, testicular steroidogenesis and testicular antioxidant enzymes levels. Concluding that DTM might disturb the testicular antioxidant level that eventually impaired the reproductive health of rats. However, LC supplementation mitigated the reproductive toxicity through its antioxidant property.
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Accepted 2023-05-10
Published 2023-09-20
References
Walker K. Cost‐comparison of DDT and alternative insecticides for malaria control. Med Vet Ent. 2000; 14(4):345-54. https://doi.org/10.1046/j.1365- 2915.2000.00262.x PMid:11129697 DOI: https://doi.org/10.1046/j.1365-2915.2000.00262.x
Wouters W, Bercken JVD. Action of pyrethroids. Gen. Pharmacol. 1978; 9:387-398. https://doi.org/10.1016/0306- 3623(78)90023-X PMid:365673 DOI: https://doi.org/10.1016/0306-3623(78)90023-X
LaForge FB, Markwood LN. Organic insecticides. Annu Rev Biochem. 1938; 1:473-90. https://doi.org/10.1146/ annurev.bi.07.070138.002353 DOI: https://doi.org/10.1146/annurev.bi.07.070138.002353
Casida JE. Pyrethrum flowers and pyrethroid insecticides. Environ. Health Perspect. 1980; 34:189-202. https:// doi.org/10.1289/ehp.8034189 PMid:6993201 PMCid: PMC1568513 DOI: https://doi.org/10.1289/ehp.8034189
Elliott M, Janes NF. Synthetic pyrethroids - A new class of insecticide. Chem Soc Rev. 1978; 1:473-505. https://doi. org/10.1039/cs9780700473 DOI: https://doi.org/10.1039/cs9780700473
Kaneko H, Ohkawa H, Miyamoto J. Degradation and movement of permethrin isomers in soil. J Pestic Sci., 1978; 3:43-51. https://doi.org/10.1584/jpestics.3.43 DOI: https://doi.org/10.1584/jpestics.3.43
Lawrence LJ, Casida J. Pyrethroid toxicology: Mouse intracerebral structure-toxicity relationships. Pestic Biochem physiol. 1982; 18:9-14. https://doi. org/10.1016/0048-3575(82)90082-7 DOI: https://doi.org/10.1016/0048-3575(82)90082-7
Daveedu T, Sainath SB. Deltamethrin induced reproductive impairment in adult male rats exposed during prepubertal stage. Int J Biol Pharm Allied Sci. 2023; 12(11).
Morgan MK. Children’s exposures to pyrethroid insecticides at home: A review of data collected in published exposure measurement studies conducted in the United States. Int J Env Res Publ Health. 2012; 9(8):2964-85. https://doi. org/10.3390/ijerph9082964 PMid:23066409 PMCid: PMC3447599 DOI: https://doi.org/10.3390/ijerph9082964
Lenz A, Lombardo F, Sgro P. Use of carnitine therapy in selected cases of male factor infertility: A double-blind crossover trial. Fertil Steril. 2003; 79:292–300. https://doi. org/10.1016/S0015-0282(02)04679-4 PMid: 12568837 DOI: https://doi.org/10.1016/S0015-0282(02)04679-4
Ng CM, Blackman MR, Wang C, Swerdloff RS. The role of carnitine in the male reproductive system. Ann N Y Acad Sci. 2004; 1033:177-88. https://doi.org/10.1196/annals.1320.017 PMid:15591015 DOI: https://doi.org/10.1196/annals.1320.017
Ishi T, Shimpo Y, Matsuoka Y, Kinositha K. Anti-apoptotic effect of acetyl-L-carnitine and L-carnitine in primary cultured neurons. Jpn J Pharmacol. 2000; 83:119–24. https:// doi.org/10.1016/S0021-5198(19)30606-7 PMid:10928324 DOI: https://doi.org/10.1016/S0021-5198(19)30606-7
Galli G, Fratelli M. Activation of apoptosis by serum deprivation in a teratocarcinoma cell line: Inhibition by L-acetylcarnitine. Exp Cell Res. 1993; 204:54–60. https:// doi.org/10.1006/excr.1993.1008 PMid:8416796 DOI: https://doi.org/10.1006/excr.1993.1008
Arrigoni-Martelli E, Caso V. Carnitine protects mitochondria and removes toxic acyls from xenobiotics. Drugs Exp Clin Res. 2001; 27:27–49.
Costa M, Canale D, Filicori M, d’lddio S, Lenzi A. Italian study group on carnitine and male infertility. L‐carnitine in idiopathic asthenozoospermia: A multicenter study. Androl. 1994; 26(3):155-9. https://doi. org/10.1111/j.1439-0272.1994.tb00780.x DOI: https://doi.org/10.1111/j.1439-0272.1994.tb00780.x
Enomoto A, Wempe MF, Tsuchida H. Molecular identification of a novel carnitine transporter specific to human testis: Insights into the mechanism of carnitine recognition. J Biol Chem. 2002; 277: 36262–271. https://doi.org/10.1074/jbc.M203883200 PMid:12089149 DOI: https://doi.org/10.1074/jbc.M203883200
Jeulin C, Lewin LM. Role of free L-carnitine and acetyl- L-carnitine in postgonadal maturation of mammalian spermatozoa. Hum Reprod Update. 1996; 2:87–102. https://doi.org/10.1093/humupd/2.2.87 PMid:9079406 DOI: https://doi.org/10.1093/humupd/2.2.87
Caviglia D, Scarabelli L, Palmero S. Effects of carnitines on rat Sertoli cell protein metabolism. Horm Metab Res. 2004; 36:221–225. https://doi.org/10.1055/s-2004-814451 PMid:15114520 DOI: https://doi.org/10.1055/s-2004-814451
Belsey MA, Moghissi KS, Eliasson R, Paulsen CA, Gallegos AJ, Prasad MR. Laboratory manual for the examination of human semen and semen-cervical mucus interaction, Singapore: Press Concern; 1980.
Talbot P, Chacon RS. A triple-stain technique for evaluating normal acrosome reactions of human sperm. J Exp Zool. 1981; 215(2):201–08. https://doi.org/10.1002/jez.1402150210 PMid:6168732 DOI: https://doi.org/10.1002/jez.1402150210
Jeyendran RS, Van Der Ven HH, Zaneveld LJD. The hypo-osmotic swelling test: An update. Arch. Androl. 1992;29(2):105–16. https://doi.org/10.3109/ 01485019208987714 PMid:1456832 DOI: https://doi.org/10.3109/01485019208987714
Blazak WF, Treinen KA, Juniewicz PE. Application of testicular sperm head counts in the assessment of male reproductive toxicity. In: Chapin RE, Heindel, Jerrold J, editors. Methods in Toxicology. Male Reproductive Toxicology. Academic Press; 1993. p. 86-94. https://doi. org/10.1016/B978-0-12-461207-5.50009-2 DOI: https://doi.org/10.1016/B978-0-12-461207-5.50009-2
Linder RE, Strader LF, Slott VL, Suarez JK. Endpoints of spermatotoxicity in the rat after short duration exposures to fourteen reproductive toxicants, Reprod Toxicol. 1992; 6:491. https://doi.org/10.1016/0890-6238(92)90034-Q PMid:1288759 DOI: https://doi.org/10.1016/0890-6238(92)90034-Q
Simon L, Carrell DT. Sperm DNA damage measured by comet assay. Methods Mol Biol. 2013; 927: 137–46. https:// doi.org/10.1007/978-1-62703-038-0_13 PMid:22992910 DOI: https://doi.org/10.1007/978-1-62703-038-0_13
Chance AC, Maehly. Assay of catalase and peroxidises. Methods Enzymol. 1955; 2:764–75. https://doi.org/10.1016/ S0076-6879(55)02300-8 DOI: https://doi.org/10.1016/S0076-6879(55)02300-8
Beutler E. The preparation of red cells for assay. In: Beutler E, editor. Red Cell Metabolism: A manual of biochemical methods. New York: Grune and Straton Company; 1975. p. 8–18.
Ohkawa H. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 44:276-8.
Brancraft JD, Stevens A. Theory and practice of histological techniques. 2nd ed. New York, USA: Chruchill Livingstone; 1982.
Sharma P, Huq AU, Singh R. Cypermethrin-induced reproductive toxicity in the rat is prevented by resveratrol. Journal of Human Reproductive Sciences. 2014; 7:99–106. https://doi.org/10.4103/0974-1208.138867 PMid:25191022 PMCid:PMC4150150 DOI: https://doi.org/10.4103/0974-1208.138867
Desai K, Moid R, Patel NPB, Highland HN. Evaluation of deltamethrin induced reproductive toxicity in male Swiss Albino mice. Asian Pac J Reprod. 2016; 5(1):24-30. https:// doi.org/10.1016/j.apjr.2015.12.004 DOI: https://doi.org/10.1016/j.apjr.2015.12.004
Aksu E, Kandemir F, Özkaraca M, Ömür A, Küçükler A, Çomaklı S. Rutin ameliorates cisplatin-induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats. Andrologia. 2017; 49(1):e12593. https://doi.org/10.1111/and.12593 PMid:27106863 DOI: https://doi.org/10.1111/and.12593
Saillenfait AM, Ndiaye D, Sabaté JP. Pyrethroids: Exposure and health effects- An update. Int J Hyg Environ Health. 2015; 218:281–92. https://doi.org/10.1016/j. ijheh.2015.01.002 PMid:25648288 DOI: https://doi.org/10.1016/j.ijheh.2015.01.002
Sengupta R, Kim J, Gomes C, Oh S, Park J, Im WB. Effect of ascorbic acid supplementation on testicular steroidogenesis and germ cell death in cadmium treated rats. Mol Cell Endocrinol. 2004; 221(1–2):57-66. https:// doi.org/10.1016/j.mce.2004.03.012 PMid:15223132 DOI: https://doi.org/10.1016/j.mce.2004.03.012
Oda SS, El-Maddawy ZKh. Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats. Exp Toxicol Pathol. 2012; 64(7-8):813-9. https://doi.org/10.1016/j.etp.2011.03.001 PMid:21478004 DOI: https://doi.org/10.1016/j.etp.2011.03.001
Eid A. Protective effect of L-carnitine against cisplatininduced testicular toxicity in rats. Al-Azhar J Ph Sci. 2016; 53(1):123–42. https://doi.org/10.21608/ajps.2016.6891 DOI: https://doi.org/10.21608/ajps.2016.6891
Okada FK. Stumpp T, Miraglia SM. Carnitine Diminishes etoposide toxic action on spermatogonial self-renewal and sperm production in adult rats treated in the prepubertal phase. J Histochem Cytochem. 2020; 0022155420916274. https://doi.org/10.1369/0022155420916274 Mid:32228279 PMCid:PMC7226625 DOI: https://doi.org/10.1369/0022155420916274
Mardanshahi T, Rezaei N, Zare Z, Shafaroudi MM, Mohammadi H. Effects of L-carnitineon the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic rats. Int J Reprod Bio Med. 2019; 17(5). https://doi.org/10.18502/ijrm.v17i5.4600 PMCid:PMC6653497 DOI: https://doi.org/10.18502/ijrm.v17i5.4600