Hepatoprotective effect of Pinostrobin against Thioacetamide-induced liver cirrhosis in rats

Abstract Pinostrobin was used in traditional medication for management of numerous syndromes. In the current study, histology, immunohistochemistry, and hepatoprotection effects of Pinostrobin were assessed against thioacetamide (TAA) hepatotoxicity in rats. Thirty rats were arbitrarily separated into five groups. Group 1 was intraperitoneally (i.p) injected with distilled water 3 times/week and fed (po) daily with 10% Tween 20 for 2 months. Group 2-5 were i.p. injected with 200 mg/kg TAA thrice weekly for 8 weeks and fed with 10% Tween 20, 50 mg/kg silymarin, 30 and 60 mg/kg of Pinostrobin daily for 8 weeks, respectively. Experimental groups fed groups showed that Pinostrobin significant reduction in liver index and hepatocyte proliferation with much lesser cell injury. These groups were significantly down-regulated the PCNA and α-SMA. The liver homogenate exhibited increased antioxidant enzymes (SOD and CAT) activities accompanied with decline in malondialdehyde (MDA) level. The serum level of bilirubin, total protein, albumin and liver enzymes (ALP, ALT, and AST) were restored to normal and were comparable to that normal control and silymarin with TAA treated groups. The hepatotoxic group showed a significant rise in serum liver biochemical markers together with a considerable decrease in protein and albumin level compared to the normal group. The hepatotoxic group displayed decreased catalase and superoxide dismutase activities while increased lipid peroxidation. Pinostrobin decreased level of TNF-a, IL-6 and increased the level of IL-10. Acute toxicity with a higher dose of 500 mg/kg Pinostrobin did not manifest any toxicological signs in rats. Macroscopy of hepatotoxic liver exhibited irregular, rough surface with micro and macro nodule. Histopathology stained by Hematoxylin and Eosin, and Masson Trichrome showed there was inflammation and infiltration of lymphocytes, focal necrosis, fibrosis, and bile duct propagation. Pinostrobin fed group had expressively reduced TAA toxicity in gross and histology as designated by fewer disturbances of hepatic tissue, slight fibrosis, and low-grade cells infiltration. Immunohistochemical staining designated that pinostrobin significantly down-regulated the expression of proliferation cellular nucleus antigen (PCNA) and alpha-smooth muscle actin (α-SMA) in theliver. Thus, the findings of this study presented that the hepatoprotective effect of this plant may be due to a reduction in toxicity, inhibition of hepatocytes proliferation, down-regulation of PCNA and α-SMA, decreased enzyme markers, and increased protein and albumin increased endogenous enzymes and reduced lipid peroxidation level.