Background: Hepatic fibrosis is a major health problem that requires further medical attention. Proton pump inhibitors are proven to possess other therapeutic potentials apart of their acid anti-secretory actions.
Aim of the work: To test possible anti-fibrotic effect of esomeprazole magnesium trihydrate in management of liver fibrosis compared to silymarin, the well-known hepatoprotective agent.
Materials & methods: 40 male albino rats were divided into 4 groups: normal control group; CCl4-treated group (1 mL/kg 40% CCl4, diluted in olive oil) I.P twice weekly for 6 weeks; esomeprazole-treated group (30 mg/kg body weight); and Silymarin-treated group (100 mg/kg body weight). Both esomeprazole and silymarin were given orally daily for two weeks after the last CCl4 dose. Serum and tissue samples were assessed for histopathological and biochemical analyses.
Results: Esomeprazole reversed hepatocellular damage, improved liver integrity, corrected major histopathological disturbances induced by CCl4 and lowered fibrosis scoring. It also improved anti-oxidant capacity and attenuated lipid peroxidation. Esomeprazole treatment resulted in down-regulation of hepatic pro-apoptotic Bax and up-regulation of anti-apoptotic Bcl2 protein expressions. In addition, it resulted in inhibition of TNF-α, TGF-β and IL-6 -mediated inflammatory responses, and retrieval of the epithelial marker e-cadherin.
Conclusion: Esomeprazole confers significant anti-fibrotic actions. Further study is needed to elucidate other probable mechanisms for this effect and to test their anti-fibrotic potential clinically.
Keywords: CCl(4); Esomeprazole; IL-6; Liver fibrosis; Proton pump inhibitors; TGF-β.
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