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In Vivo Attenuation of Alcohol- and Cadmium Chloride–Induced Testicular Toxicity Modulated by Silymarin in Male Wistar Rat

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Abstract

The aim of the study is to investigate the in vivo attenuation of alcohol- and cadmium chloride–induced testicular toxicity modulated by Silymarin in male Wistar rats. A total of fifty-six (56) Wistar rats were used for this study and they were randomized into seven (7) groups of eight (8) rats each. Group 1 was control rats; Groups 2–7 served as the experimental groups. After 6 weeks treatment duration, the rats were euthanized, semen was collected for semen analysis, blood samples for testosterone, and FSH and LH assay determination, and left testes was harvested for histological analysis. One-way ANOVA was used to compare means at p-level < 0.05 was considered significant. Findings from this study have shown that alcohol and cadmium chloride adversely affected semen parameters, testosterone, and FSH and LH hormone milieu. Data also showed that Silymarin administration attenuated the adverse effect of alcohol and cadmium chloride on semen quality and hormones associated with reproductive functions. Hence, Silymarin mopped the effect of in vivo attenuation of alcohol and cadmium chloride testicular damage. The findings of this study have further established that alcohol and cadmium chloride adversely affected semen parameters, testicular alterations, and serum hormonal milieu. However, the effect was more significantly deleterious in rats exposed to cadmium chloride when compared to rats exposed to alcohol, subsequently alcohol- and cadmium chloride–induced degeneration of testicular tissues. Furthermore, Silymarin administration attenuated the adverse effect of alcohol on semen quality and hormones associated with reproductive functions.

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Data Availability

The data that supports the findings of this study are available from the corresponding author on request and approval from all authors.

References

  1. Raghuveer C, Chawala VK, Soni ND, Jayant K, Vyas RK (2010) Oxidative stress and role of antioxidants in male infertility. Pak J Physiol 6(2):54–59

    Google Scholar 

  2. Sharma P, Jha AB, Dubey RS, Pessarakli M (2012) Reactive oxygen species, oxidative damage, and antioxidative defense mechanism in plants under stressful conditions. J Bot 2(1):12–20

    Google Scholar 

  3. Strassburger D, Schaster M, Soffer Y, Ron-El R (2002) Factors influencing the outcome of ICSI in patients with obstructive and non-obstructive azoospermia: a comparative study. Hum Reprod 17:3114–3121

    Article  PubMed  Google Scholar 

  4. Skakkebaek NE, Rajpert-De ME, Main KM (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum Reprod 16:972–978

    Article  CAS  PubMed  Google Scholar 

  5. Sallmen M, Weinberg CR, Baird DD, Lindbohm ML, Wilcox AJ (2005) Has human fertility declined over time? Why we may never know. Epidemiology 16:494–499

    Article  PubMed  Google Scholar 

  6. Tan SW, Meiller JC, Mahaffey KR (2009) The endocrine effects of mercury in humans and wildlife. Crit Rev Toxicol 39(3):228–269

    Article  CAS  PubMed  Google Scholar 

  7. Panjehpour M, Bayesteh M (2008) The cytotoxic effects of cadmium chloride on the human lung carcinoma (Calu-6) cell line. Res in Pharm Sci 3(2):49–53

    Google Scholar 

  8. World Health Organization (2004) Global status report on alcohol. Accessed from: http:// www.who.int/entity/substance_abuse/publication/global_status_report_2004_overview.pdf Accessed 16th November, 2019

  9. Bhardwaj JK, Sharma RK (2011) Changes in trace elements during follicular atresia in caprine ovary. Biol Trace Elem Res 140:291–298

    Article  CAS  PubMed  Google Scholar 

  10. Talabi AR, Sarchesmeh AA, Khalili MA, Tabibreyad N (2011) Effects of ethanol consumption on chromatin condensation and DNA integrity of epididymal spermatozoa in rat. Alcohol 45(4):403–409

    Article  CAS  Google Scholar 

  11. Homan GF, Davies M (2007) The impact of lifestyle factors on reproductive performance in the general population and those undergoing infertility treatment: a review. Hum Reprod Update 13(3):209–223

    Article  CAS  PubMed  Google Scholar 

  12. Muthusami KR, Chinnaswamy P (2005) Effect of chronic alcoholism on male fertility hormones and semen quality. Fertil Steril 84:919–924

    Article  CAS  PubMed  Google Scholar 

  13. Singh RP, Tyagi AK, Zhao J, Agarwal R (2002) Silymarin inhibits growth and causes regression of established skin tumors in SENCAR mice via modulation of mitogen-activated protein kinases and induction of apoptosis. Carcinogenesis 3(3):499–510

    Article  Google Scholar 

  14. Julin B (2012) Dietary cadmium exposure and risk of postmenopausal breast cancer: a population-based prospective cohort study. Cancer Res 72:1459–1466

    Article  CAS  PubMed  Google Scholar 

  15. Patel SP, Sullivan PG, Lyttle TS, Rabchevsky AG (2010) Acetyl-L-carnitine ameliorates mitochondrial dysfunction following contusion spinal cord injury. J Neurochem 114:291–301

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang MJ, Lin WW, Chen HL, Chang YH, Ou HC, Kuo JS, Hong JS, Jeng KCG (2002) Silymarin protects dopaminergic neurons against lipopolysaccharide - induced neurotoxicity by inhibiting microglia activation. Eur J Neurosci 16:2103–2112

    Article  PubMed  Google Scholar 

  17. Brzóska MM, Galażyn-Sidorczuk M, Dzwilewska I (2013) Ethanol consumption modifies the body turnover of cadmium: a study in a rat model of human exposure. J Appl Toxicol 33(8):784–798

    Article  PubMed  CAS  Google Scholar 

  18. Atef MMA, Fatma AAI, Noha AAE, Samir WA (2014) Antioxidant effects of curcumin against cadmium chloride-induced oxidative stress in the blood of rats. J Pharmacog Phytother 6(3):33–40

    Article  Google Scholar 

  19. Saleh RA, Agarwal A (2002) Oxidative stress and male infertility: from research bench to clinical practice. J Androl 23:737–752

    CAS  PubMed  Google Scholar 

  20. Seed J, Robert C, Clegg ED, Dostal LA, Foote RH, Hurtt ME, Gary RK, Makris SL, Perreault SD, Schrader SM, Seyler D, Sprando R, Treinen KA, Veeramachaneni DN, Wise LD (1996) Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. Reprod Toxicol 10(3):237–244

    Article  CAS  PubMed  Google Scholar 

  21. Bonnet X, Naulleau G, Bradshaw D, Shine R (2001) Changes in plasma progesterone in relation to vitellogenesis and gestation in the viviparous snake Viperaaspis. Gen Comp Endocrinol 121:84–94

    Article  CAS  PubMed  Google Scholar 

  22. Bancroft JD, Gamble MR (2002) Theory and practice of histological techniques; 5th. Ed. Edinburgh. Churchill Livingstone Pub. 172-175: 593-620

  23. Blanco A, Moyano R, Vivo J (2007) Quantitative changes in the testicular structure in mice exposed to low doses of cadmium. Environ Toxicol Pharmacol 23:96–101

    Article  CAS  PubMed  Google Scholar 

  24. Lafuente A, Esquifino AI (2002) Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male. Toxicol Lett 110:209–218

    Article  Google Scholar 

  25. Lafuente A, Marquez N, Perez-Lorenzo M, Pazo D, Esquifino AI (2000) Pubertal and postpubertal cadmium exposure differentially affects the hypothalamic-pituitary- testicular axis function in the rat. Food & Chem Toxicol 38:913–923

    Article  CAS  Google Scholar 

  26. Li LH, Heindel JJ (1998) Sertoli cell toxicants. In: Korach KS (ed) Reproductive and developmental toxicology. Marcel Dekker, New York, pp 655–691

    Google Scholar 

  27. Rinaldi M, Micali A, Marini H, Adamo EB, Puzzolo D, Pisani A, Trichilo V, Altavilla D, Squadrito F, Minutoli L (2017) Cadmium, organ toxicity and therapeutic approaches: a review on brain, kidney and testis damage. Curr Med Chem 24(35):3879–3893

    Article  CAS  PubMed  Google Scholar 

  28. Lafuente A, Marquez N, Piquero S, Esquifino AI (1999) Cadmium affects the episodic luteinizing hormone secretion in male rats: possible age-dependent effects. Toxicol Lett 104:27–33

    Article  CAS  PubMed  Google Scholar 

  29. Akang EN, Oremosu AA, Dosumu OO, Ejiwunmi AB (2011) The role of Telfairiaoccidentalis in protecting the testis against alcohol induced damage. Maced J Med Sci 4:380–387

    Article  Google Scholar 

  30. Frias J, Rodriguez R, Torres JM, Ruiz E, Ortega E (2000) Effects of acute alcohol intoxication on pituitary gonadal axis hormones, pituitary adrenal axis hormones, beta-endorphin and prolactin in human adolescents of both sexes. Life Sci 67:1081–1086

    Article  CAS  PubMed  Google Scholar 

  31. Ren J, Banan A, Keshavarzian A, Zhu Q, LaPaglia N, McNulty J (2005) Exposure to ethanol induces oxidative damage in the pituitary gland. Alcohol 35:91–101

    Article  CAS  PubMed  Google Scholar 

  32. Ellingboe J, Varanelli CC (1979) Ethanol inhibits TT biosynthesis by direct action on Leydig cells. Res Commun Chem Pathol Pharmacol 24(1):87–102

    CAS  PubMed  Google Scholar 

  33. Chiao YB, Johnston DE, Gavaler SJ, Van Thiel DH (2008) Effect of chronic feeding on testicular content of enzymes required for testosteronogenesis. Alcohol Clin Exp Res 5(2):230–236

    Article  Google Scholar 

  34. Adler RA (1992) Clinically important effects of alcohol on endocrine function. J Clin Endocrinol Metabol 74:957–960

    CAS  Google Scholar 

  35. Zhu Q, Meisinger J, Emanuelle NV (2000) Ethanol exposure enhances apoptosis within the testes. Alcohol Clin Exp Res 24:1550–1556

    Article  CAS  PubMed  Google Scholar 

  36. Kefer JC, Agarwal A, Sabanegh E (2009) Role of antioxidants in the treatment of male infertility. Int J Urol 16:449–457

    Article  CAS  PubMed  Google Scholar 

  37. Trappoliere M, Caligiuri A, Schmid M, Bertolani C, Failli P, Vizzutti F, Novo E, Di Manzano C, Marra F, Loguercio C (2009) Silybin, a component of sylimarin, exerts anti-inflammatory and anti-fibrogenic effects on human hepatic stellate cells. J Hepatol 50:1102–1111

    Article  CAS  PubMed  Google Scholar 

  38. Van-Thiel DH, Galaver PK, Rosenblum E, Eagon YB (1987) Effects of ethanol on endocrine cells: testicular effects. Ann N Y AcadSci 492:287–302

    Article  CAS  Google Scholar 

  39. Frias J, Torres JM, Miranda MT, Ruiz E, Ortega E (2002) Effects of acute alcohol intoxication on pituitary–gonadal axis hormones, pituitary–adrenal axis hormones, B-Endorphin and prolactin in human adults of both sexes. Alcoh Alcoh 37:169–173

    Article  CAS  Google Scholar 

  40. Bhardwaj JK, Kumari P, Saraf P, Yadav AS (2018) Antiapoptotic effects of vitamins C and E against cypermethrin-induced oxidative stress and spermatogonial germ cell apoptosis. J BiochemMol Toxicol 32(8):e22174

  41. Bhardwaj JK, Saraf P, Kumari P, Mittal M, Kumar V (2018) N-Acetyl-cysteine mediated inhibition of spermatogonial cells apoptosis against malathion exposure in testicular tissue. J Biochem Mol Toxicol. 32(4): e22046

  42. Bhardwaj JK, Panchal H (2021) Quercetin mediated attenuation of cadmium induced oxidative toxicity and apoptosis of spermatogenetic cells in caprine testes in vitro. Environ Mol Mutagen 62(6):374–384

    Article  CAS  PubMed  Google Scholar 

  43. Hew KW, Ericson WA, Welsh MJ (1993) A single low cadmium dose cause failure of spermiation in the rat. Toxicol Appl Pharmacol 12:15–21

    Article  Google Scholar 

  44. Bhardwaj JK, Palliwal A, Saraf P (2021) Effects of heavy metals on reproduction owing to infertility. J. Biochem. Mol. Toxicol. 35(8):1-21. e22823

    Article  CAS  Google Scholar 

  45. Rikans LE, Yamano T (2000) Mechanisms of cadmium acute hepatotoxicity. J Biochem Mol Toxicol 14:110–117

    Article  CAS  PubMed  Google Scholar 

  46. Valenzuela A, Garrido A (1994) Biochemical bases on the pharmacological action on the flavonoids silymarin and of its structural isomer silibinin. Biol Res 27:105–112

    CAS  PubMed  Google Scholar 

  47. Sarah F, Samual B, Roland E, Titilayo A (2012) Testicular toxicity and sperm quality fallowing cadmium exposure in rat: ameliorative potentials of allium cepa. J hum Reprod Sci 2:37

    Google Scholar 

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All authors participated in the design, interpretation of the studies, and analysis of the data and gave final approval of the manuscript. EB, NBC, AE, OO, NA, EEI, and NEK conducted the experiments, EB and NEK conceptualized, designed, and wrote the manuscript, NBC and OO drafted and critically revised the manuscript, AE, NA, and EEI contributed to analysis, methodology, and interpretation. All authors read and approved the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Bartholomew Chukwuebuka Nwogueze.

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Enebeli, B., Nwangwa, E.K., Nwogueze, B.C. et al. In Vivo Attenuation of Alcohol- and Cadmium Chloride–Induced Testicular Toxicity Modulated by Silymarin in Male Wistar Rat. Biol Trace Elem Res 200, 3666–3676 (2022). https://doi.org/10.1007/s12011-021-02944-3

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