title: Effects of nicotine on the testicular toxicity of streptozotocin-induced diabetic rat: intervention of enalapril.
abstract: The aim of the present study is to investigate whether nicotine augmented the testicular toxicity and angiotensin converting enzyme inhibitor, enalapril, can ameliorate the effects in diabetic rat. Male Sprague Dawley rats were randomized into five groups: control, nicotine, diabetic, Diab + Nico, and Diab + Nico + Enal. Animals were made diabetic by single injection of streptozotocin (55 mg/kg/intraperitoneally). Nicotine dissolved in drinking water at a concentration of 100 µg/ml was given ad libitum and enalapril was given orally at a dose of 10 mg/kg/day for four consecutive weeks. After 4 weeks of treatment, animals were killed and biochemical parameters glucose, glycosylated hemoglobin, cotinine, and the testosterone levels were measured. Testicular toxicity was evaluated using sperm count, sperm comet assay, histology, and immunohistochemical staining of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and the proinflammatory markers (nuclear factor kappa B (NF-κB), cyclooxygenase (COX-2), and tissue necrotic factor alpha (TNF-α)) evaluated by western blotting. Results showed that nicotine did not alter the blood glucose and glycosylated hemoglobin level, significantly decreased the sperm count and increased the sperm DNA damage. These changes were accompanied by significant increases in the 8-oxo-dG, NF-κB, COX-2, and TNF-α expression. Furthermore, the intervention of enalapril in nicotine-treated diabetic rat attenuated the testicular damage and restored sperm count, sperm DNA damage, as well as reduced the expression of NF-κB, COX-2, and TNF-α. These findings clearly suggest that nicotine not only augmented the testicular toxicity in the diabetic rat but also increases the risk of germ cell toxicity effects that were attenuated by enalapril treatment.
authors.affiliation: Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research, Punjab, India.
authors.forename: S
authors.initials: S
authors.lastname: Kushwaha
authors.affiliation: Department of Pharmacology and Toxicology, Facility for Risk Assessment and Intervention Studies, National Institute of Pharmaceutical Education and Research, Punjab, India gbjena@gmail.com.
authors.forename: G B
authors.initials: GB
authors.lastname: Jena
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D051546:Cyclooxygenase 2 / Q000378:metabolism; D019610:Cytoprotection; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004656:Enalapril / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D013076:Sperm Count; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013311:Streptozocin; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D016328:NF-kappa B; D018722:Nicotinic Agonists; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D004656:Enalapril; D009538:Nicotine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D003849:Deoxyguanosine
keywords: DNA damage; Nicotine; diabetes; enalapril; testes