Abstract
Background: Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used in the treatment of HIV infections and has been reported to be toxic to the male reproductive system. This study was designed to evaluate the ameliorative effects of kolaviron (KV), a biflavonoid from Garcinia kola, on NVP-induced testicular toxicity.
Methods: The adult male Wistar rats were given two and four times therapeutic doses of NVP (NVP-2T and NVP-4T; 18 and 36 mg/kg NVP) alone or in combination with KV (200 mg/kg). NVP was given daily, whereas KV was administered five times in a week by oral gavage.
Results: Treatment with NVP did not alter the body weight gain and relative weight of testis of the rats. NVP-4T significantly (p<0.05) decreased the sperm motility, protein content, and live-dead ratio and also increased the percentage sperm abnormalities of the rats. Although NVP-4T significantly increased sperm abnormalities, it has no effect on epididymal sperm count. Also, NVP-4T caused a significant (p<0.05) elevation of serum aminotransferases and γ-glutamyl transferase activities. In addition, NVP-4T significantly (p<0.05) decreased the levels of testicular superoxide dismutase, catalase, glutathione S-transferase, and glutathione with marked elevation of malondialdehyde (index of lipid peroxidation) in the rats. In contrast, NVP-2T did not produce an adverse effect on the biochemical indices studied in testes and sperm of rats. Supplementation with KV significantly ameliorated the biochemical changes caused by NVP-4T.
Conclusions: Taken together, KV reversed the adverse effects of NVP-4T on testicular antioxidant enzymes and markers of oxidative stress in the rats.
References
1. Warren KJ, Boxwell DE, Kim NY, Drolet BA. Nevirapine-associated Stevens-Johnson syndrome. Lancet 1998;351:567.10.1016/S0140-6736(98)24008-6Search in Google Scholar
2. Fagot JP, Mockenhaupt M, Bouwes-Bavinck JN, Naldi L, Viboud C, Roujeau JC; EuroSCAR Study Group. Nevirapine and the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis. AIDS 2001;15:1843–8.10.1097/00002030-200109280-00014Search in Google Scholar
3. Adaramoye OA, Adesanoye OA, Adewumi OM, Akanni O. Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats. Hum Exp Toxicol 2012;31:676–85.10.1177/0960327111424304Search in Google Scholar
4. Halliwell B, Grootveld M. The measurement of free radical reactions in humans: some thoughts for future experimentation. FEBS Lett 1987;213:9–14.10.1016/0014-5793(87)81455-2Search in Google Scholar
5. Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ. A series of prostaglandin F2–like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA 1990;87:9383–7.10.1073/pnas.87.23.9383Search in Google Scholar
6. Morrow JD, Roberts LJ. Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress. Methods Enzymol 1999;300:3–12.10.1016/S0076-6879(99)00106-8Search in Google Scholar
7. Roberts LJ, Morrow JD. Isoprostanes as markers of lipid peroxidation in atherosclerosis. In: Serhan CN, Ward PA, editors. Molecular and cellular basis of inflammation. Totowa, NJ: Humana Press, 1999:141–63.Search in Google Scholar
8. Farombi EO, Adepoju BF, Ola-Davies OE, Emerole GO. Chemoprevention of aflatoxin B1-induced genotoxicity and hepatic oxidative damage in rats by kolaviron, a natural biflavonoid of Garcinia kola seeds. Eur J Cancer Prev 2005;14:207–14.10.1097/00008469-200506000-00003Search in Google Scholar PubMed
9. Adaramoye OA, Adeyemi EO. Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seed. Basic Clin Pharmacol Toxicol 2006;98:135–41.10.1111/j.1742-7843.2006.pto_256.xSearch in Google Scholar PubMed
10. Iwu MM, Igboko OA, Okunji CO, Tempesta MS. Anti-diabetic and aldose reductase activities of biflavanones of Garcinia kola. J Pharm Pharmacol 1990;42:290–2.10.1111/j.2042-7158.1990.tb05412.xSearch in Google Scholar PubMed
11. Adaramoye OA, Adeyemi EO. Hypoglycaemic and hypolipidaemic effects of fractions from kolaviron, a biflavonoid complex from Garcinia kola in streptozotocin-induced diabetes mellitus rats. J Pharm Pharmacol 2006;8: 121–8.Search in Google Scholar
12. Adaramoye OA, Farombi EO, Adeyemi EO, Emerole GO. Inhibition of human low-density lipoprotein oxidation by flavonoids of Garcinia kola seeds. Pak J Med Sci 2005;21:331–9.Search in Google Scholar
13. Iwu MM. Antihepatotoxicity of Garcinia kola seeds. Experientia 1985;41:679–700.10.1007/BF02007729Search in Google Scholar PubMed
14. Cotterhill PJ, Scheinmann F, Stenhouse TA. Extractives from Guttiferae kolaflavanone, a new biflavanone from the nuts of Garcinia kola Heckel. J Chem Soc Perkin Trans 1978; 1:246.Search in Google Scholar
15. Adaramoye OA, Awogbindin I, Okusaga JO. Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on ethanol-induced oxidative stress in liver of adult Wistar rats. J Med Food 2009;12:584–90.10.1089/jmf.2008.0138Search in Google Scholar
16. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265–75.10.1016/S0021-9258(19)52451-6Search in Google Scholar
17. Mohun AF, Cook LJ. Simple method for measuring serum level of glutamate-oxaloacetate and glutamate-pyruvate transaminases in laboratories. J Clin Pathol 1957;10:394–9.10.1136/jcp.10.4.394Search in Google Scholar
18. Reitman S, Frankel S. A colorimetric method for the determination of serum level of glutamate-oxaloacetate and pyruvate transaminases. Am J Clin Pathol 1957;28:56–63.10.1093/ajcp/28.1.56Search in Google Scholar
19. Fossati R, Melzid’Eril GV, Turenghi G, Precipe L, Berti G. A kinetic colorimetric assay of γ-glutamyltransferase. Clin Chem 1986;32:1581–4.10.1093/clinchem/32.8.1581Search in Google Scholar
20. King EJ, Armstrong AR. Calcium, phosphorus and phosphatases. In: Varley H, editor. Practical clinical biochemistry. New Delhi: CBS Publishers, 1988:458–9.Search in Google Scholar
21. Walls R, Kumar KS, Hochstein P. Aging human erythrocytes. Differential sensitivity of young and old erythrocytes to hemolysis induced by peroxide in the presence of thyroxine. Arch Biochem Biophys 1976;176:463–8.10.1016/0003-9861(76)90374-XSearch in Google Scholar
22. Moron MA, Depierre JW, Mannervick B. Levels of glutathione, glutathione reductase and glutathione-S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582:67–78.10.1016/0304-4165(79)90289-7Search in Google Scholar
23. McCord JM, Fridovich I. Superoxide dismutase, an enzymatic function for erythrocuperin. J Biol Chem 1969;244: 6049–55.Search in Google Scholar
24. Aebi H. Catalase. In: Bergmeyer HV, editor. Methods of enzymatic analysis. New York: Verlag Chemie, 1974:673–84.Search in Google Scholar
25. Habig WH, Pabst MJ, Jakoby WB. Glutathione-S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 1974;249:7130–9.10.1016/S0021-9258(19)42083-8Search in Google Scholar
26. Zemjanis R. Diagnostic and therapeutic technique in animal reproduction: collection and evaluation of semen. Baltimore: William and Wilkins Co., 1970:139–53 pp.Search in Google Scholar
27. Rezvanfar M, Sadrkhanlou R, Ahmadi A, Shojaei-Sadee H, Rezvanfar M, Mohammadirad A, et al. Protection of cyclophosphamide-induced toxicity in reproductive tract histology, sperm characteristics, and DNA damage by an herbal source; evidence for role of free-radical toxic stress. Hum Exp Toxicol 2008;27:901–10.10.1177/0960327108102046Search in Google Scholar PubMed
28. Pant N, Srivastava SP. Testicular and spermatotoxic effects of quinalphos in rats. J Appl Toxicol 2003;23:271–4.10.1002/jat.919Search in Google Scholar PubMed
29. Wells ME, Awa OA. New technique for assessing acrosomal characteristics of spermatozoa. J Dairy Sci 1970;53:227.10.3168/jds.S0022-0302(70)86184-7Search in Google Scholar
30. Gilbert DL, Colton CA. Reactive oxygen species in biological systems: an interdisciplinary approach. New York: Kluwer Academic/Plenum Publishers, 1999:138–45 pp.Search in Google Scholar
31. Sies H. Oxidative stress: introduction. In: Oxidative stress, oxidant and antioxidants. San Diego, CA: Academic Press, 1991:15–22 pp.Search in Google Scholar
32. Trush MA, Kensler TW. An overview of the relationship between oxidative stress and chemical carcinogenesis. Free Radic Biol Med 1991;10:201–9.10.1016/0891-5849(91)90077-GSearch in Google Scholar
33. Siems WG, Grune T, Esterbauer H. 4-Hydroxynonenal formation during ischemia and reperfusion of rats small intestine. Life Sci 1995;57:785–9.10.1016/0024-3205(95)02006-5Search in Google Scholar
34. Wang MY, Dhingra K, Hittelman WN, Liehr JG, deAndrade M, Li DH. Lipid peroxidation-induced putative malondialdehyde-DNA adducts in human breast tissues. Cancer Epidemiol Biomarkers Prev 1996;5:705–10.Search in Google Scholar
35. Aitken RJ. Generation of reactive oxygen species, lipid peroxidation and human sperm function. Biol Rep 1989; 40:183–97.10.1095/biolreprod41.1.183Search in Google Scholar
36. Lopes S, Jurisicova A, Sun J, Casper RF. Reactive oxygen species: a potential cause for DNA fragmentation in human spermatozoa. Hum Reprod 1998;13:896–900.10.1093/humrep/13.4.896Search in Google Scholar
37. Kaplan MM. Laboratory tests. In: Schiff L, Schiff ER, editors. Diseases of the liver, 7th ed. Philadelphia: JB Lippincott, 1993:108–44 pp.Search in Google Scholar
38. Guoyao W, Yun-Zhong F, Sheng Y, Joanne R, Nancy D. Glutathione metabolism and its implications for health. J Nutr 2004;134:489–92.10.1093/jn/134.3.489Search in Google Scholar
39. Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Annu Rev Pharmacol Toxicol 2005;45:51–88.10.1146/annurev.pharmtox.45.120403.095857Search in Google Scholar
40. Dröge W. Metabolische Störungen bei HIV-Infektion (Metabolic disturbances with HIV infection). In: Project News; No. 2. Berlin, Germany: AIDS-Zentrum des Bundesgesundheitsamtes, 1989:4 pp.Search in Google Scholar
41. Halliwell B. Free radicals, antioxidants and human diseases, curiosity, causes or consequence. Lancet 1994;344:720–4.10.1016/S0140-6736(94)92211-XSearch in Google Scholar
42. Smith GJ, Ohl VS, Litwack G. The glutathione-S-transferases and chemically induced hepato-carcinogenesis: a review. Cancer Res 1977;37:8–14.Search in Google Scholar
43. Vernet P, Aitken RJ, Drevet JR. Antioxidant strategies in the epidydimis. Mol Cell Endocrinol 2004;216:31–9.10.1016/j.mce.2003.10.069Search in Google Scholar PubMed
44. Farombi EO, Shrotriya S, Surh YJ. Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-κB and AP-1. Life Sci 2009;84:149–55.10.1016/j.lfs.2008.11.012Search in Google Scholar PubMed
45. Farombi EO, Abarikwu SO, Adedara IA, Oyeyemi MO. Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats. Basic Clin Pharmacol Toxicol 2007;100:43–8.10.1111/j.1742-7843.2007.00005.xSearch in Google Scholar PubMed
46. Farombi EO, Ugwuezunmba MC, Ezenwadu TT, Oyeyemi MO, Ekor M. Tetracycline induced reproductive toxicity in male rats: effects of vitamin C and N-acetylcysteine. Exp Toxicol Pathol 2008;60:77–85.10.1016/j.etp.2008.02.002Search in Google Scholar PubMed
47. Farombi EO, Nwaokeafor IA. Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats. Clin Exp Pharmacol Physiol 2005;32:667–74.10.1111/j.0305-1870.2005.04248.xSearch in Google Scholar PubMed
©2013 by Walter de Gruyter Berlin Boston
Articles in the same Issue
- Masthead
- Masthead
- Review
- Heat: not black, not white. It’s gray!!!
- Original Articles
- Distribution of performance-related gene polymorphisms (ACTN3 R577X and ACE ID) in different ethnic groups of the Indian Army
- Birth month and longevity: birth month of victims of sudden (SCD, ≤1 h) and rapid (RCD, ≤24 h) cardiac deaths
- Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) polymorphism is associated with chronic inflammatory periodontitis. A cross-sectional study
- The effect of coadministration of α-tocopherol and ascorbic acid on arsenic trioxide-induced testicular toxicity in adult rats
- Effect of acute immobilization stress with or without a heme oxygenase inducer on testicular structure and function in male albino rats
- Effect of Jobelyn® on intruder- and isolation-induced aggressive behavior in mice
- Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory T-cell differentiation in alloreactive human lymphocytes
- Antinociceptive, anti-inflammatory and antiulcerogenic activities of ethanol root extract of Strophanthus hispidus DC (Apocynaceae)
- Acrolein-induced inflammatory signaling in vascular smooth muscle cells requires activation of serum response factor (SRF) and NFκB
- Nephroprotective activity of Cocculus hirsutus leaf extract in 5/6 nephrectomized rat model
- Toxicological evaluations of methanolic extract of Moringa oleifera leaves in liver and kidney of male Wistar rats
- Nevirapine induces testicular toxicity in Wistar rats: reversal effect of kolaviron (biflavonoid from Garcinia kola seeds)
- Toxicity of Chevron Escravos crude oil and chemical dispersant on guinea pig testicular function
- Jobelyn® pretreatment ameliorates symptoms of psychosis in experimental models
Articles in the same Issue
- Masthead
- Masthead
- Review
- Heat: not black, not white. It’s gray!!!
- Original Articles
- Distribution of performance-related gene polymorphisms (ACTN3 R577X and ACE ID) in different ethnic groups of the Indian Army
- Birth month and longevity: birth month of victims of sudden (SCD, ≤1 h) and rapid (RCD, ≤24 h) cardiac deaths
- Hyperpolarization-activated cyclic nucleotide-gated 2 (HCN2) polymorphism is associated with chronic inflammatory periodontitis. A cross-sectional study
- The effect of coadministration of α-tocopherol and ascorbic acid on arsenic trioxide-induced testicular toxicity in adult rats
- Effect of acute immobilization stress with or without a heme oxygenase inducer on testicular structure and function in male albino rats
- Effect of Jobelyn® on intruder- and isolation-induced aggressive behavior in mice
- Dichloroacetate at therapeutic concentration alters glucose metabolism and induces regulatory T-cell differentiation in alloreactive human lymphocytes
- Antinociceptive, anti-inflammatory and antiulcerogenic activities of ethanol root extract of Strophanthus hispidus DC (Apocynaceae)
- Acrolein-induced inflammatory signaling in vascular smooth muscle cells requires activation of serum response factor (SRF) and NFκB
- Nephroprotective activity of Cocculus hirsutus leaf extract in 5/6 nephrectomized rat model
- Toxicological evaluations of methanolic extract of Moringa oleifera leaves in liver and kidney of male Wistar rats
- Nevirapine induces testicular toxicity in Wistar rats: reversal effect of kolaviron (biflavonoid from Garcinia kola seeds)
- Toxicity of Chevron Escravos crude oil and chemical dispersant on guinea pig testicular function
- Jobelyn® pretreatment ameliorates symptoms of psychosis in experimental models