Investigation of hepatic and renal toxicity induced by omeprazole in CCl4 injury mouse model

Omeprazole belongs to a class of drugs called proton pump inhibitors (PPIs). It is routinely used to treat stomach ailments. PPIs are known to induce the cytochrome P450 pathway, an important modulator of liver damage leading to liver fibrosis. Most concerning is the ever increasing number of cases of acute interstitial nephritis (AIN) associated with PPI therapy. It appears to be a class effect as all PPIs have been documented to cause AIN. Several adverse drug event registries now note PPIs as the most common cause of drug-induced AIN. The aim of this study was to investigate the hepatic and renal toxicity caused by omeprazole. A liver injury mouse model was designed by intraperitoneal treatment of CCl4 with olive oil (1:1) for twenty-one days. One of the groups of CCl4 given mice was treated with orally given omeprazole treatment for fifteen days. Serological and biochemical analysis revealed that ALT, AST, ALP, creatinine, and urea levels were increased and levels of total protein and albumin were significantly decreased in the omeprazole group as compared to control. Histopathological studies of hepatic tissues revealed the degree of cellular injury with infiltration of cells and disturbed hepatic structure after treatment with omeprazole compared to control. Expression of (CYP1A1, CYP1A2, CYP2E1, IL6, IL1β, MYD88, collagen, α-SMA, TLR4, TLR9) showed a significant increase in omeprazole treated group. In conclusion, our results demonstrated omeprazole, a hepatotoxic drug. However, further research is needed to finally establish the regime.