Investigation of the protective effectiveness of malus sylvestris extract on thioacetamide-induced chronic liver fibrosis

In this study, the protective capacity of the ethanol extract of Malus sylvestris (MS) against thioacetamide (TAA)-induced experimental liver fibrosis was investigated using histopathological, immunohistochemical, and biochemical methods. A total of 24 rats were used in the study and randomly divided into four groups: Control, MS, TAA, and TAA+MS. While the Control group rats were fed a standard pellet diet, the MS group received 200 mg/kg MS extract orally once daily; the TAA group was administered 100 mg/kg TAA intraperitoneally three times a week; and the TAA+MS group received both treatments 200 mg/kg MS extract orally once daily and 100 mg/kg TAA intraperitoneally three times a week. At the end of the one-month experimental period, necropsy was performed, and liver tissues were collected for histopathological analysis, while blood and liver tissue samples were subjected to biochemical evaluation. Biochemical analysis revealed no significant difference in AST levels between the Control and MS groups, whereas the TAA group showed a significantly elevated AST level compared to all other groups. In the TAA+MS group, AST levels were significantly higher than in the Control and MS groups but significantly lower than in the TAA group. Analysis of ALT levels showed a significant increase in the TAA group. In the TAA+MS group, ALT levels were significantly higher compared to the Control and MS groups; however, there was no significant difference compared to the TAA group. Regarding HDL levels, the Control and MS groups exhibited significantly higher HDL levels than the other groups. The TAA+MS group showed higher HDL levels compared to the TAA group but lower levels compared to the Control and MS groups. These results suggest that MS extract increased HDL levels in the TAA+MS group.Evaluation of LDL levels revealed no significant difference between the Control and MS groups. However, LDL levels were significantly elevated in the TAA group (p < 0.05), while the TAA+MS group showed a significant reduction compared to the TAA group. Serum TAS and SOD levels were significantly lower in the TAA group than in the other groups, whereas these levels were significantly higher in the TAA+MS group compared to the TAA group. TOS levels were significantly elevated in the TAA group relative to the other groups, but MS supplementation in the TAA+MS group significantly reduced TOS levels compared to the TAA group. TAA administration led to significant increases in caspase-3 and hydroxyproline levels in rats. In contrast, MS administration in the TAA+MS group significantly reduced these levels. No significant differences in caspase-3 and hydroxyproline levels were observed between the Control and MS groups. Tissue TAS levels were significantly decreased in the TAA group compared to the Control and MS groups, whereas MS administration in the TAA+MS group led to a partial (p > 0.05) increase in TAS levels. Tissue TOS levels were significantly higher in the TAA group than in the Control and MS groups, but MS treatment significantly reduced these levels in the TAA+MS group (p < 0.05). Tissue SOD levels were significantly lower in the TAA group than in the other groups (p < 0.05), while MS administration significantly increased SOD levels in the TAA+MS group (p < 0.05). Tissue levels of caspase-3 and hydroxyproline were also significantly elevated by TAA treatment, whereas MS administration in the TAA+MS group significantly reduced these levels (p < 0.05). Histopathological and immunohistochemical evaluation of liver tissue samples revealed that the marked degenerative, necrotic, and fibrotic changes observed in the TAA group were significantly reduced in the TAA+MS group following MS administration. These findings indicate that Malus sylvestris extract exhibits protective efficacy against fibrotic changes in TAA-induced liver fibrosis.