Iris gatesii foster: Acute toxicity and Hepatoprotective effects of against thioactamid-induced liver Cirrhosis in rats via modulation of PCNS/TGF-β1pathways

Iris gatesii is a well-known therapeutic plant used in Kurdish folk medicine for the treatment of inflammation and tumors. We evaluated the acute toxicity and hepatoprotective effects of methanolic extracts of Iris gatesii (MEIG) against thioacetamide (TAA)-induced liver injury in rats. Albino Dawley rats (30) were clustered into five groups: normal (A) and TAA control rats (B) treated with daily distilled water; reference rats received three oral doses of 50 mg/kg silymarin; D and E, rats received daily doses of 250 and 500 mg/kg MEIG, respectively. In addition, groups B-E received three injections of 200 mg/kg TAA in a week for 60 days. The hepatotoxic results revealed a noticeably lower hepatic injury in MEIG-treated rats, as indicated by the reduced liver index and hepatocyte proliferation. Histopathological evaluation (H&E and Masson trichrome staining) showed significant inhibitory potential of MEIG on the incidence rate of hepatic lesions, represented by decreased liver necrosis and lower fibrous connective tissue proliferation initiated by TAA in rats. MEIG treatment significantly downregulated proliferating cell nuclear antigen (PCNA) in the liver and spleen parenchymal tissues. Moreover, MEIG-treated rats had lower TGF-β1 tissue expression, higher antioxidants (SOD, CAT, and GPx), and reduced MDA content in hepatic tissues compared to cirrhotic control rats. Pro-inflammatory cytokines (IL-10) were negatively modulated, and anti-inflammatory cytokines were noticeably higher in MEIG-treated rats than in cirrhotic control rats. In addition, MEIG treatment significantly restored serum liver biomarkers (enzymes and proteins) in TAA-induced hepatotoxicity.