Tetracycline-induced reproductive toxicity in male rats: effects of vitamin C and N-acetylcysteine.
Tetracycline, a broad-spectrum antibiotic employed clinically in the treatment of bacteria infections, is known to cause a number of biochemical dysfunctions and suspected to induce testicular damage to animals and humans, but there is paucity of data on its effect and mechanism of action on the male reproductive system. The present study therefore evaluates its spermatotoxic and testicular toxicity in male rats and the chemoprotective effects of Vitamin C (Vit C) and N-acetylcysteine (NAC). Tetracycline was administered orally at the dose level of 28.6 mg/kg body weight per day in two equal divided doses (12h interval). Vit C and NAC were also administered orally to the rats at doses of 200 and 50 mg/kg body weight per day, respectively, for the 14 days of the experiment. While there was no change in the body weights of rats, tetracycline administration caused significant decrease in the relative weights of testis, epididymis and seminal vesicles (P<0.05). Administration of tetracycline caused a reduction in the epididymal sperm motility, percentage of live spermatozoa, sperm count, and an increase in abnormal sperm morphology, as well as induction of adverse histopathologic changes in the testes. While Vit C and NAC significantly mitigated the toxic effect of tetracycline on sperm parameters, the antioxidants did not improve the adverse histopathologic changes induced by antibiotic. Treatment of rats with tetracycline significantly decreased the activities of superoxide dismutase, catalase (CAT), glucose-6-phosphate dehydrogenase, glutathione-S-transferase (GST) and the levels of GSH and serum testosterone, while the activity of gamma-glutamyltranspeptidase and the formation of malondialdehyde (MDA) increased. Both Vit C and NAC significantly attenuated the toxic effects of tetracycline to the antioxidant and testicular marker enzymes as well as markers of oxidative stress. Collectively, the results suggest that therapeutic dose of tetracycline elicits spermatotoxic and testicular toxicity in male rats through induction of oxidative stress. The chemoprotective effects of Vit C and NAC during tetracycline treatment suggest that these antioxidants may find clinical application in cellular damage involving reactive oxygen species (ROS).
Farombi
Ebenezer O
EO
Drug Metabolism and Toxicology Research Laboratories, Department of Biochemistry College of Medicine, University of Ibadan, Nigeria. olatunde_farombi@yahoo.com
Ugwuezunmba
Mercy C
MC
Ezenwadu
Teclar T
TT
Oyeyemi
Matthew O
MO
Ekor
Martins
M
D000111:Acetylcysteine / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D004359:Drug Therapy, Combination; D016166:Free Radical Scavengers / Q000494:pharmacology*; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000097:blood; D005982:Glutathione Transferase / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D013733:Testicular Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D013752:Tetracycline / Q000633:toxicity*
D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D013739:Testosterone; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D013752:Tetracycline; D005978:Glutathione; D001205:Ascorbic Acid; D000111:Acetylcysteine