The antifibrotic effect of Zilla spinosa extracts targeting apoptosis in CCl4-induced liver damage in rats

الملخص EN

Background/aim Liver fibrosis and its end-stage cirrhosis are the main reasons of morbidity and mortality all over the world.

The current study aimed to evaluate the efficacy of Zilla spinosa (Z.

spinosa) on CCl4-induced liver fibrosis, apoptosis, and oxidative stresses in rats.

Materials and methods Extract of aerial part of Z.

spinosa was used in this study.

Thirty male Sprague? Dawley rats were enrolled in this study and divided into five groups (six each): group 1 served as control and groups 2–5 were treated with CCl4 (1 ml/ kg intraperitoneal twice a week for 8 weeks), where group 2 served as a control positive, group 3 received silymarin (50 mg/kg) daily, and groups 4 and 5 were administrated with Z.

spinosa (100 and 200 mg/kg, respectively) daily for 8 weeks.

At the end of each experiment, liver function tests were analyzed in serum, whereas malondialdehyde (MDA), Nitric oxide (NO), Glutathione (GSH), and hydroxyproline (HA) were analyzed in liver tissues.

Liver fibrosis was confirmed histopathologically, and collagen content, caspase-3, and α-smooth muscle actin (α-SMA) were assayed immunhistochemically.

Results Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, MDA, NO, and HA levels were increased (P<0.05), whereas total protein and GSH were decreased (P<0.05) in CCl4-administrated rats.

Histopathological results showed loss of lobular structure, fibrosis with expansion of portal tract by fibrous tissue together with inflammatory changes confined to portal tract and central vein, and intense centrilobular necrosis and remarkable fatty hydropic degeneration.

In addition, extensive accumulation of connective tissue, marked depletion of glycogen, strong expression of α-SMA, and increased of caspase-3 were found in CCl4-administrated rats.

Oral administration of Z.

spinosa at 100 or 200 mg/kg restored the normal levels of liver function parameters, MDA, NO and GSH; decreased HA; and reduced collagen, glycogen content, caspase-3, and α-SMA in liver tissue of rats.

The high dose of 200 mg/kg showed more potent effect than low dose of 100 mg/kg when compared with silymarin treatment group.

Conclusion The present study clarified that Z.

spinosa extract has antioxidant and antiapoptotic properties in CCl4-induced liver fibrosis in rats, and may be able to exert a therapeutic effect on developing hepatic fibrosis; moreover, high dose of 200 mg/kg appeared to be more potent than low dose (100 mg/kg).