Esomeprazole ameliorates CCl4 induced liver fibrosis in rats via modulating oxidative stress, inflammatory, fibrogenic and apoptotic markers.

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.