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Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs

  • Harikrishnan Radhakrishnakartha , Abhilash Puthuvelvippel Appu und Indira Madambath EMAIL logo


Background: Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol.

Methods: Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA).

Results: There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results.

Conclusions: Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.

Corresponding author: Indira Madambath, Department of Biochemistry, University of Kerala, Thiruvananthapuram-695 581, India, Phone: 0471-2308078, Fax: 0471-2308078, E-mail:

Financial assistance in the form of a Research Fellowship in Science to Meritorious Students (RFSMS) sponsored by UGC is gratefully acknowledged.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


1. Lebold KM, Grant KA, Freeman WM, Wiren KM, Miller GW, Kiley C, et al. Individual differences in hyperlipidemia and vitamin E status in response to chronic alcohol self-administration in cynomolgus monkeys. Alcohol Clin Exp Res 2011;35:474–83.10.1111/j.1530-0277.2010.01364.xSuche in Google Scholar

2. McDonough KH. Antioxidant nutrients and alcohol. Toxicology 2003;189:89–97.10.1016/S0300-483X(03)00155-0Suche in Google Scholar

3. Seitz HK, Kuhn B, von Hodenberg E, Fiehn W, Conradt C, Simanowski UA. Increased messenger RNA levels for low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver after long-term ethanol ingestion. Hepatology 1994;20:487–93.Suche in Google Scholar

4. Sweedy MA, Hamid NA, Moselhy ME. The role of a mixture of green tea, turmeric and chitosan in the treatment of obesity-related testicular disorders. J Appl Biomed 2007;5:131–8.10.32725/jab.2007.018Suche in Google Scholar

5. Muthusami KR, Chinnaswamy P. Effect of chronic alcoholism on male fertility hormones and semen quality. Fertil Steril 2005;84:919–24.10.1016/j.fertnstert.2005.04.025Suche in Google Scholar PubMed

6. Villalta J, Ballesca JL, Nicolas JM, Martinez de Osaba MJ, Antunez E, Pimentel C. Testicular function in asymptomatic chronic alcoholics: relation to ethanol intake. Alcohol Clin Exp Res 1997;21:128–33.10.1097/00000374-199702000-00019Suche in Google Scholar

7. Khalili MA, Zare-Zadeh N, Hashemi H. Correlation between serum lipids profile with sperm parameters of infertile men with abnormal semen analysis. Iran J Reprod Med 2009;7:123–7.Suche in Google Scholar

8. Venkatesh V, Sharma JD, Raka Kamal. A comparative study of effect of alcoholic extracts of Sapindus emarginatus, Terminalia belerica, Cuminum cyminum and Allium cepa on reproductive organs of male albino rats. Asian J Exp Sci 2002;16:51–63.Suche in Google Scholar

9. Aruna K. Ascorbic acid in the testis and accessory sex-organs of bat, Cynopterus sphinx (vahl) during the reproductive cycle. AJBB [internet] 2012;1:1(e105) 6 pages. Available at: http://www.ajbbonline.com/Issue1_May2012.html.Suche in Google Scholar

10. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn Rev 2010;4:11826.10.4103/0973-7847.70902Suche in Google Scholar PubMed PubMed Central

11. Biswas NM, Chaudhari A, Sarkar M, Biswas R. Effect of ascorbic acid on in vitro synthesis of testosterone in rat testis. Indian J Exp Biol 1996;34:612–3.Suche in Google Scholar

12. Asha GS, Indira M. Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs. Comp Biochem Physiol C Toxicol Pharmacol 2004;137:109–14.10.1016/j.cca.2003.12.002Suche in Google Scholar PubMed

13. Abdulaziz MA. Amelioration of high cholesterol diet caused lipids accumulation in hepatic cells by rutin and ascorbic acid. Br J Pharmacol Toxicol 2013;4:56–64.10.19026/bjpt.4.5378Suche in Google Scholar

14. Hume CW. The UFAW Handbook on the Care and Management of Laboratory Animals. Edinburgh/London: Churchill Livigstone, 1972.Suche in Google Scholar

15. Green CR, Watts LT, Kobus SM, Henderson GI, Reynolds JN, Brien JF. Effects of chronic prenatal ethanol exposure on mitochondrial glutathione and 8-iso-prostaglandin F2alpha concentrations in the hippocampus of the perinatal guinea pig. Reprod Fertil Dev 2006;18:517–24.10.1071/RD05128Suche in Google Scholar PubMed

16. Harikrishnan R, Abhilash PA, Das SS, Prathibha P, Rejitha S, John F, et al. Protective effect of ascorbic acid against ethanol-induced reproductive toxicity in male guinea pigs. Br J Nutr 2013;110:689–98.10.1017/S0007114512005739Suche in Google Scholar PubMed

17. Reitman S, Frankel SA. Colorimetric method for determination of serum glutamic oxaloacetic and glutamic pyruvic transaminases. Am J Clin Pathol 1957;28:56–63.10.1093/ajcp/28.1.56Suche in Google Scholar

18. Folch J, Lees M, Stanley S. A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 1957;226:497–509.10.1016/S0021-9258(18)64849-5Suche in Google Scholar

19. Abell LL, Levy BB, Brodie BB, Kendall FE. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 1952;195:357–66.10.1016/S0021-9258(19)50907-3Suche in Google Scholar

20. Van Handel E, Zilversmit DB. Micromethod for the direct determination of the serum triglyceride. J Lab Clin Med 1957;50:150–57.Suche in Google Scholar

21. Falholt K, Lund B, Falholt W. An easy colorimetric micro method for routine determination of free fatty acid in plasma. Clin Chem Acta 1973;46:105–10.10.1016/0009-8981(73)90016-8Suche in Google Scholar

22. Zilversmith DB, Davis AK. Microdetermination of plasma phospholipids by trichloroacetic acid precipitation. Lab Clin Med 1950;35:155–60.Suche in Google Scholar

23. Rao AV, Ramakrishnan S. Estimation of HMG CoA reductase activity. Clin Chem 1975;21:1523.Suche in Google Scholar

24. Kornberg A, Horecker BL. Glucose-6-phosphate dehydrogenase. In: Colowick SP, Kaplan NO, editors. Methods in enzymology. NewYork: Academic Press, 1955:323–7.Suche in Google Scholar

25. Ochoa S. Malic enzyme. In: Colowick SP, Kaplan NO, editors. Methods in enzymology. New York: Academic Press, 1955:739–53.Suche in Google Scholar

26. Vallee B, Hoch F. Yeast alcohol dehydrogenase, a zinc metalloenzyme. J Am Chem Soc 1955;77:821–22.10.1021/ja01608a103Suche in Google Scholar

27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951;193:265–75.10.1016/S0021-9258(19)52451-6Suche in Google Scholar

28. Bancroft D, Stevens A, Turmer R, editors. Theory and practice of histological technique, 4th ed. Edinburgh, London, Melbourne: Churchill Livingstone, 1996:47–67.Suche in Google Scholar

29. Johnson AD, Gomes WR, Free MJ, VanDemark NL. Testicular lipids. III. Effect of surgery and unilateral or bilateral cryptorchidism. J Reprod Fertil 1968;16:409–14.10.1530/jrf.0.0160409Suche in Google Scholar

30. Oshima M, Carpenter MP. The lipid composition of the prepubertal and adult rat testis. Biochim Biophys Acta 1968;152:479–97.10.1016/0005-2760(68)90089-1Suche in Google Scholar

31. Connor WE, Lin DS, Neuringer M. Biochemical markers for puberty in the monkey testis: desmosterol and docosahexaenoic acid. J Clin Endocrinol Metab 1997;82:1911–6.10.1210/jc.82.6.1911Suche in Google Scholar

32. Sharaf AA, El-Din AK, Hamdy MA, Hafeiz AA. Effect of ascorbic acid on oxygen consumption, glycolysis and lipid metabolism of diabetic rat testis. Ascorbic acid and diabetes I. J Clin Chem Clin Biochem 1978;16:651–5.Suche in Google Scholar

33. Frenoux JM, Vernet P, Volle DH, Britan A, Saez F, Kocer A, et al. Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymis structure and functions. J Mol Endocrinol 2004;33:361–75.10.1677/jme.1.01515Suche in Google Scholar PubMed

34. Ashakumary L, Vijayammal PL. Additive effect of alcohol and nicotine on lipid peroxidation and antioxidant defence mechanism in rats. J Appl Toxicol 1996;16:305–8.10.1002/(SICI)1099-1263(199607)16:4<305::AID-JAT353>3.0.CO;2-FSuche in Google Scholar

35. Balasubramaniyan V, Manju V, Nalini N. Effect of leptin administration on plasma and tissue lipids in alcohol induced liver injury. Hum Exp Toxicol 2003;22:149–51.10.1191/0960327103ht337oaSuche in Google Scholar

36. Davis BK. Timing of fertilization in mammals: sperm cholesterol/phospholipid ratio as a determinant of the capacitation interval. Proc Natl Acad Sci USA 1981;78:7560–4.10.1073/pnas.78.12.7560Suche in Google Scholar

37. Shimamoto K, Sofikitis N. Effect of hypercholesterolemia on testicular function and sperm physiology. Yonago Acta Medica 1998;41:23–9.Suche in Google Scholar

38. Gorden GG, Southern AL. Metabolic effects of alcohol on the endocrine system. In: Lieber CS, editor. Metabolic aspects of alcoholism. Baltimore: University Park Press, 1977:249–72.Suche in Google Scholar

39. Dosumu OO, Duru FIO, Osinubi AA, Oremosu AA, Noronha CC. Influence of virgin coconut oil (VCNO) on oxidative stress, serum testosterone and gonadotropic hormones (FSH, LH) in chronic ethanol ingestion. Agric Biol J North Am 2010;1:1126–32.10.5251/abjna.2010.1.6.1126.1132Suche in Google Scholar

40. Bartke A. Effects of prolactin and luteinizing hormone on the cholesterol stores in the mouse testis. J Endocrinol 1971;49:317–24.10.1677/joe.0.0490317Suche in Google Scholar

41. Bartke A, Musto N, Caldwell BV, Behrman HR. Effects of a cholesterol esterase inhibitor and of prostaglandin F2alpha on testis cholesterol and on plasma testosterone in mice. Prostaglandins 1973;1:97–104.10.1016/0090-6980(73)90141-XSuche in Google Scholar

42. Scott TW, Voglmayr JK, Setchell BP. Lipid composition and metabolism in testicular and ejaculated ram spermatozoa. Biochem J 1967;102:456–61.10.1042/bj1020456Suche in Google Scholar

43. Awano M, Kawaguchi A, Mohri H. Lipid composition of hamster epididymal spermatozoa. J Reprod Fertil 1993;99:375–83.10.1530/jrf.0.0990375Suche in Google Scholar

44. Bangur CS, Howland JL, Katyare SS. Thyroid hormone treatment alters phospholipid composition and membrane fluidity of the rat brain mitochondria. Biochem J 1955;305:29–32.10.1042/bj3050029Suche in Google Scholar

45. Haidl G, Opper C. Changes in lipids and membrane anisotropy in human spermatozoa during epididymal maturation. Hum Reprod 1997;12:2720–23.10.1093/humrep/12.12.2720Suche in Google Scholar

46. Gomathi C, Balasubramanian K, Bhanu NV, Srikanth V, Govindarajulu P. Effect of chronic alcoholism on semen studies on lipid profiles. Int J Androl 1993;16:175–81.10.1111/j.1365-2605.1993.tb01176.xSuche in Google Scholar PubMed

47. Ramirez-Torres MA, Carrera A, Zambrana M. High incidence of hyperestrogenemia and dyslipidemia in a group of infertile men. Ginecol Obstet Mex 2000;68:224–29.Suche in Google Scholar

48. Srikanth V, Balasubramanian K, Govindarajulu P. Effects of ethanol treatment on Leydig cellular NADPH-generating enzymes and lipid profiles. Endocr J 1995;42:705–12.10.1507/endocrj.42.705Suche in Google Scholar PubMed

49. Shirai T, Ikemoto I. Mechanism of alcoholic testicular damage. Nihon Hinyokika Gakkai Zasshi 1992;83:305–14.Suche in Google Scholar

50. Takeda K, Yamauchi M, Ohata M, Sakamoto K, Nakajima H, Hirakawa J. Association between testicular atrophy and muscular atrophy after ethanol administration. Jikeikai Med J 2003;50:37–43.Suche in Google Scholar

Received: 2012-9-25
Accepted: 2013-9-19
Published Online: 2013-10-24
Published in Print: 2014-02-01

©2014 by Walter de Gruyter Berlin Boston

Heruntergeladen am 6.12.2023 von https://www.degruyter.com/document/doi/10.1515/jbcpp-2012-0056/html?lang=de
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