Deciphering inhibitory potential of Proton Pump Inhibitors on novel oncogenic biomarker TRPM7 using targeted approach

Abstract

Proton Pump Inhibitors (PPIs) ranks among the most widely used drugs for gastric related disorders worldwide. They are under vigilance since past few years owing to numerous adverse effects including ionic disturbances to alteration in bone remodeling process. They have been repurposed as anticancer agent, targeting various pathways but the relationship with the novel oncogenic biomarker, TRPM7 has not being studied. Hence, the present study was intended to identify the inhibitory potential of PPIs on oncogenic biomarker, which is a cationic channel. This targeted protein channel has its regulation based on ionic balance, which made an alert for also assessing putative adverse effects of PPIs specifically for ionic balance. Hence, the study was initiated by screening the adversity of PPIs followed by interaction study of TRPM7 channel and PPIs. newlinePreliminary work was performed by carrying out an in-vivo study in wistar rats. The animals were administered with Pantoprazole (30mg/kg/day, p.o), Rabeprazole newline(20mg/kg/day,p.o) and Esomeprazole(5mg/kg/day,p.o) for a duration of 8 weeks. Assessment of the adverse effects so performed showed ionic imbalance, reflected newlineincreased in serum creatinine and urea level owing to an increase in risk for kidney injury, decrease in bone strength and ionic imbalance related variations in ECG newlinepatterns. Esomeprazole showed maximal kidney injury risk and detrimental effect on bone as compared to other PPIs. Together with adversity, impact on TRPM7 was also newlineassessed which showed PPIs treated groups to have reduced concentration of TRPM7 in tissues collected (Colon, pancreas, prostate and ovary) with minor alterations. newlineHowever, Pantoprazole (30mg/kg/day, p.o) showed progressive decrease among all the tissues. newlineIn-silico molecular docking was the next study performed to validate the interaction observed from in-vivo study for expression of TRPM7.