Hepatoprotective Effect of Diosmin on Iron-induced Liver Damage

Research Abstract

Background and Objectives: Liver injury is an ascending healthcare challenge. The aim of the present investigation was to elucidate the possible protective effect of diosmin against ferrous sulfate-induced liver injury in adult male albino rats. Methodology: Animals were divided into 6 groups; group 1: normal control (tween 80, p.o., 10 days), group 2: N-acetylcysteine control(300 mg/kg/day, p.o., 10 days), group 3: diosmin control (20 mg/kg/day, p.o., 10 days), group 4: ferrous sulphate (two doses of ferrous sulfate, 30 mg/kg/day, i.p., at 9th and 10th day), group 5: N-acetylcysteine (300 mg/kg/day, p.o., 10 days) plus ferrous sulphate (two doses of ferrous sulfate, 30 mg/kg/day, i.p., at 9th and 10th day), and group 6: diosmin (20 mg/kg/day, p.o., 10 days) plus ferrous sulphate (two doses of ferrous sulfate, 30 mg/kg/day, i.p., at 9th and 10th day). On the 11th day, blood and tissue samples were collected. Statistical analysis was carried out using one way ANOVA test followed by Tukey-Kramer multiple comparisons test, with value of p < 0.05 considered significant. Results: Iron-induced liver injury was evidenced by significant increase in hepatocyte membrane damage markers (serum ALT, AST, ALP, GGT, LDH and bilirubin), oxidative and inflammatory markers (hepatic MDA content and NOx production), and dyslipidemic markers (serum TC and TG) (p < 0.05). In addition, significant decreases in hepatic GSH content and serum albumin were noted (p < 0.05). Treatment with diosmin significantly improved hepatocyte membrane damage markers (showing reductions ranging from 24% to 48%), oxidative and inflammatory markers (showing 34% and 32% reductions regarding MDA and NOx, respectively), dyslipidemic markers (showing 35% and 39% reductions regarding serum TC and TG respectively) (p < 0.05). Histopathological investigation of liver sections, in addition to immunohistochemical investigations of iNOS and eNOS in liver sections, strongly supported biochemical findings. Conclusion: Diosmin may have good hepatoprotective effect, mostly through antioxidant and anti-inflammatory potentials. Modulation of NOS expression may have a key role in such protection.

Research Keywords

Diosmin; ferrous sulphate; N-acetylcysteine; hepatotoxicity; eNOS; iNOS; oxidative stress markers.