Effect of Proton Pump Inhibitors on Hepatic Regeneration

Abstract

Introduction: The liver is critical in multiple processes, including the clearance of endogenous compounds, the synthesis of macromolecules, and organ-specific biotransformation processes. Therefore, the liver’s regenerating capacity is of vital importance. Multiple pathways are activated in the complex process that leads to hepatic regeneration. In the present study, we aimed to evaluate the effect of proton pump inhibitors omeprozole, lansoprazole, and pantoprazole on hepatic regeneration following partial hepatectomy. Materials and Methods: Four groups were formed with 32 rats in each. Partial liver resections were performed for all animals. Omeprazole (71.4 µg/day), lansoprazole (107 µg/day), pantoprazole (143 µg/day) and placebo (0.5 cm³) were administered to the groups respectively. A quarter of the rats in each group were sacrificed on the 1st postoperative day. The rest were sacrificed on the 3rd, 5th and 7th postoperative days. The remnant regenerating liver mass was removed and weighed, and Ki-67 monoclonal antibody levels were measured. Results: There was no statistical difference between the four groups on the first day in evaluating the weight of the liver mass (p = 0.09) and Ki-67 (p = 0.268) levels. Only the omeprazole group showed a difference; the Ki-67 level was lower in the omeprazole group on the 3rd (p = 0.003, p = 0.0001, p = 0.003), 5th (p = 0.017, p = 0.001, p = 0.0001) and 7th (p = 0.0001) days compared to the other groups. Also the weight of the remnant liver mass was lower in the omeprazole group on the 3rd, 5th and 7th (p = 0.0001) days. Conclusion: We figured out that lansoprazole and pantoprazole have no effects on liver regeneration, whereas omeprazole showed a negative effect on hepatic regeneration.

Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans

“…Experimental evidence in rats suggests that PPI administration limits the regenerative capacity of livers following partial hepatectomy. 55 Administration of PPI upregulates expression of mRNA and protein level and results in increased activity of the heme oxygenase-1 enzyme in gastric and endothelial cells. 56 Heme oxygenase-1 is generally seen as salutary, but its beneficial properties are vitiated at higher doses, and with sustained duration of expression.…”

Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury

“…Experimental evidence in rats suggests that PPI administration limits the regenerative capacity of the liver after partial hepatectomy. 25 It is unclear whether PPI exposure also limits the regenerative capacity of renal tubular cells, for example. Such a mechanism, if verified, may at least partially explain the increased risk of renal outcomes in PPI users.…”

The role of proton pump inhibitors in renal disease - the risk of using OTC drugs

“…Badania z udziałem zwierząt wykazały z kolei związek między stosowaniem IPP a osłabieniem zdolności regeneracyjnych wątroby, co sprzyja trwałemu jej uszkodzeniu. Niewykluczone staje się zatem, że postępująca dysfunkcja nerek mogłaby postępować w podobny, jeszcze niepoznany sposób [17,1]. Inną teorię prezentują natomiast Morschel i wsp., wskazując hipomagnezemię oraz proces zapalny jako główne czynniki przyczyniające się do rozwoju AKI oraz CKD [18].…”

“…Mechanism of kidney damage as a result of breakdown of proton pump inhibitors (based on the diagram fromMorschel et al[17]). …”