Cirrhosis induced by thioacetamide is prevented by stevia. Molecular mechanisms

This study aimed to investigate the ability of stevia leaves to prevent thioacetamide (TAA)-induced cirrhosis in rats, explore the action mechanism involved, and evaluate whether the plant could prevent striatal dopamine turnover alterations in cirrhotic rats. TAA increased collagen, hepatic stellate cell (HSC) activation and induction of the profibrogenic mediators involved in the canonical and non-canonical transforming growth factor-β1 (TGF-β1) pathways, including nuclear factor-κB (NF-κB) and proinflammatory cytokine production, malondialdehyde, and 4-hydroxynonenal, whereas GSH/GSSG and nuclear erythroid factor 2 (Nrf2) were decreased. TAA-treated rats exposed to Mn²⁺ had altered striatal dopamine turnover. Stevia partially or completely prevented all of these effects. Stevia showed antioxidant, anti-inflammatory and antifibrotic properties, probably because of its capacity to induce Nrf2 to reduce NF-κB and block several profibrogenic routes, inhibiting activation of HSCs, thus preventing fibrosis and dopamine turnover.