Omeprazole Prevents Colistin-Induced Nephrotoxicity in Rats: Emphasis on Oxidative Stress, Inflammation, Apoptosis and Colistin Accumulation in Kidneys

Abstract

The clinical value of colistin, a polymyxin antibiotic, is limited by its nephrotoxicity. Omeprazole is a commonly prescribed proton pump inhibitor. The current study aimed to evaluate the effects of the concomitant administration of omeprazole on colistin-induced nephrotoxicity in rats. Omeprazole significantly ameliorated colistin nephrotoxicity as evidenced by prevention in the rise in the serum level of creatinine, urea and cystactin C as well as urinary N-acetylglucosamine activity. This was confirmed by histological studies that indicated a decreased incidence of interstitial nephritis, degenerative cortical changes and collagen deposition. This was accompanied by the prevention of oxidative stress as omeprazole significantly inhibited the lipid peroxidation, glutathione depletion and enzymatic exhaustion of superoxide dismutase as well as catalase. Additionally, omeprazole inhibited the expression of interleukin-6 and tumor necrosis factor-α. Further, omeprazole inhibited the colistin-induced rise in Bax and the down-regulation of Bcl2 mRNA expression. An assessment of the serum levels of colistin revealed that omeprazole had no significant impact. However, it was observed that omeprazole significantly inhibited the accumulation of colistin in kidney tissues. In conclusion, omeprazole protects against colistin-induced nephrotoxicity. This can be attributed to, at least partly, omeprazole’s anti-oxidant, anti-inflammatory and anti-apoptotic activities in addition to its ability to prevent the toxic accumulation of colistin in kidneys.

Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses

“…In vitro studies showed synergistic interaction of polymyxin with a range of non-antibiotic drugs [31]. The use of omeprazole prevented polymyxin E-induced nephrotoxicity in a rat model and was used in some horses concurrently to PolyB [32]. Metamizol on the other hand is reported to cause acute kidney injury in a low number of human patients and might have also influenced renal function in horses concurrently treated with this antipyretic drug in the present study [33].…”

The Potential Gastro-Protective Effect of Qaysum (Achillea fragrantissima) Against Ethanol-Induced Gastric Ulcer in Wistar Albino Rats

“…In the present research, AFE, as well as the administration of omeprazole, also showed a significant decline in MDA but significantly increased CAT, GSH, and SOD levels in the serum and gastric homogenates versus the positive control group. The study reported important antioxidant effects of omeprazole along with its acid-suppression activities [23].…”

Correction: Nasrullah et al. Omeprazole Prevents Colistin-Induced Nephrotoxicity in Rats: Emphasis on Oxidative Stress, Inflammation, Apoptosis and Colistin Accumulation in Kidneys. Pharmaceuticals 2022, 15, 782

“…In the original publication [ 1 ], there was a mistake in Figure 2. There was an error in the sub-image of the first row, last column.…”