Investigation on sodium valproate induced germ cell damage, oxidative stress and genotoxicity in male Swiss mice

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 32; no. 4; pp. 385 - 394
• Main Authors: Khan, Sabbir, Ahmad, Tauseef, Parekh, Chintan Vishnubhai, Trivedi, Priyanka Pushkarbhai, Kushwaha, Sapana, Jena, Gopabandhu
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2011; Elsevier
• Subjects: Animals; Anticonvulsants - toxicity; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; DNA Damage; Embryology: invertebrates and vertebrates. Teratology; Epididymis - pathology; Fundamental and applied biological sciences. Psychology; Genotoxicity; Germ cell; Male; Medical sciences; Mice; Mutagens - toxicity; Neuropharmacology; Organ Size - drug effects; Oxidative Stress; Pharmacology. Drug treatments; Sodium valproate; Sperm Count; Sperm Head - drug effects; Spermatozoa - abnormalities; Spermatozoa - drug effects; Teratology. Teratogens; Testis - chemistry; Testis - metabolism; Testis - pathology; Toxicology; Valproic Acid - toxicity; Germ cell; Oxidative stress; Mice; Sodium valproate; Genotoxicity; 4-Aminobutyrate transaminase; Enzyme; Toxicity; Transferases; Rodentia; Enzyme inhibitor; Male; Anticonvulsant; Valproic acid; Germinal cell; Histone deacetylase inhibitor; Vertebrata; Mammalia; Mouse; Mood stabilizer; Transaminases; Animal; DNA
• DOI: 10.1016/j.reprotox.2011.09.007
• ISSN: 0890-6238

► Present study reported the role of VPA-induced oxidative stress leading to DNA damage and germ cell toxicity in mice. ► Present results reported at clinical relevant doses, which can aid realistic picture for human risk assessment in clinical setups. ► In present study, we successfully reported the genotoxic potential of VPA as revealed by sperm comet assay in the rodent model. Sodium valproate (VPA) is the most widely used antiepileptic drug for the treatment of epilepsy, bipolar psychiatric disorders and migraine. However, long-term VPA treatment has several adverse effects on the reproductive system. The present study was aimed to investigate the possible germ cell toxicity of VPA in mice. Animals were treated with VPA intraperitoneally for 10 and 28 days at the doses of 500 mg/kg-d and 100, 200 and 400 mg/kg-d, respectively, and were sacrificed 24 h after the last dose. The germ cell toxicity of VPA was assessed using oxidative stress parameters, sperm count, sperm head morphology, sperm comet assay, 8-oxo-dG expression and histology. VPA treatment significantly decreased the sperm count, testes and epididymis weight and significantly increased the sperm head abnormality, sperm DNA damage, oxidative stress and 8-oxo-dG expression in the testes of mice. The present study illustrates that VPA induced germ cell toxicity in mice.