Vonoprazan mitigates diethyl nitrosamine-induced acute liver injury in mice via modulating p-AMPK/ SIRT1/ PGC-1α and Keap1/Nrf2/HO-1 pathways.

BACKGROUND

Vonoprazan (VON), a potassium-competitive acid blocker, is used in the treatment of acid-related disorders including GERD, gastritis, and esophagitis besides H. pylori infection.

AIM: This study was carried out to elucidate the hepatoprotective effect of VON against diethylnitrosamine (DN)-induced acute liver injury (ALI) in mice.

METHOD: Thirty-six male mice were randomly alienated into six groups, including control group, VON20 group, DN-induced ALI group, VON5 + DN group, VON10 + DN group and VON20 + DN group. ALI was induced in mice using DN (150 mg/kg, i.p.). VON was orally administered at three doses (5, 10 and 20 mg/kg) for 7 days before DN injection, and DN was injected on day 7.

RESULTS

In comparison to DN group, VON exerted hepatoprotective effect, evidenced by significant decrease in serum levels of ALT, AST, GGT and LDH. Additionally, VON administration restored oxidant/anti-oxidant balance, as presented by significant decrease in hepatic levels of MDA in addition to profound increase in hepatic level of GSH and TAC. Furthermore, VON administration attenuated DN-induced reduction in hepatic levels of p-AMPK, SIRT1, PGC-1α, Nrf2 and HO-1. VON also induced significant reduction in hepatic levels of Keap1, NF-κB and TNF-α when compared to DN. Histopathologically, VON mitigated DN-induced histopathological irregularities in hepatic tissues.

CONCLUSION

VON suggests hepatoprotective potential, in a dose dependent manner, possibly due to their antioxidant and anti-inflammatory properties.