Expression of Inducible Nitric Oxide Synthase in N-Acetyl-p-aminophenolinduced Hepatotoxicity following Ameliorative Role of Ascorbic Acid in Wistar rat

Recent findings show conflicting evidences of both beneficial and deleterious effects of inducible nitric oxide synthase (iNOS). Ascorbic acid (ACA) is a source of antioxidant. This study seeks to examine the role of iNOS in acetaminophen (APAP)-induced liver damage following treatment with ACA. Twenty (20) female rats (150-200g) were used for the study, which were divided into four groups (A-D) n=5. Group A received normal saline while groups B-D received 2700 mg/kg of paracetamol for 21 days. Later, Groups C and D were orally treated with 200 mg/kg and 500 mg/kg body weight of ACA respectively for 21 days and group B was left untreated. Rats were sacrificed 24hours after the last administration. Blood and liver tissues were collected for biochemical, immunohistochemical and histological assays. One-way ANOVA was used to analyze data. Graph pad Prism 5 was used for analysis, p-values ? 0.05 were considered statistically significant. iNOS was strongly expressed across the groups. Collagen fibre was densely expressed in groups A and C while elastic fibre was densely distributed in A and D. ALT showed significant (p= 0.05) increase in APAP group while AST was increased only in ACA-treated groups. SGPT was increased significantly in ACA-treated groups while SGOT showed no differences across groups. TBARS was increased significantly (p=0.05) in group ACA-treated groups when compared with control. We conclude that iNOS is not only expressed in damaged tissues, as other underlying processes could lead to its expression in normal tissue. ACA was instrumental in ameliorating APAP liver damage.

Key Words: iNOS; Acetaminophen; Hepatoprotective, Ascorbic acid, hepatotoxicity; Ameliorative