Discovery of novel ketamine‐inspired derivatives as a protective agent against renal ischemic/reperfusion injury in Wistar rats

Abstract

Renal ischemia‐reperfusion (I/R) injury is a limiting factor for the success of renal grafts and is deemed greatly responsible for the mortality. A novel series of ketamine‐inspired compounds was synthesized and subjected to NF‐ĸB transcriptional inhibitory activity in LPS‐stimulated RAW264.7 cells, where entire set of compounds showed mild‐to‐moderate significant NF‐ĸB transcriptional inhibitory activity (IC50 6.53–67.52 µM). Compound 6d showed highest inhibitory activity among the tested series (IC50 2.62 µM) and found more potent as compared to ketamine as standard. The effect of compound 6d was further quantified in I/R injury in Wistar rats, where it dose‐dependently improves kidney function of rats with significant amelioration of kidney injury as suggested by histopathologic examination of renal tissues. It further showed reduction in the generation of pro‐inflammatory cytokines and improves the antioxidant status of experimental rats. Compound 6d inhibited apoptosis and increases the expression of Bcl2 and decreases Bax, and cleaved caspase‐3 level. It further reduces TLR‐4 and NF‐κB expression in renal cells of rats, with increases in IκB‐α level in Western blot analysis as compared to I/R group. In summary, our current study showed the development of a novel class of ketamine‐inspired derivatives against renal ischemia/reperfusion injury.

The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation

“…Anesthetics such as ketamine and propofol have been reported to have antioxidant and protective effects in various organs, especially the kidney and brain (Xing et al 2022;Zhu and Zhang 2022). As mentioned earlier, many studies in the literature examine the harmful or protective effects of many anesthetics on other organs.…”

The renal protective efficacy of ketamine vs. propofol vs. ketofol against renal ischemia / reperfusion injury: An experimental rat study

“…Research has demonstrated that it exhibits a protective effect against IRI, although the exact molecular mechanisms involved are still unclear [6][7][8][9]. Ketamine has been shown to reduce the generation of pro-inflammatory cytokines, to attenuate induced lipid peroxidation, and also to enhance renal antioxidant status, thus exhibiting a protective effect against renal IRI [6,8]. Ketofol consists of a combination of propofol 0.5mg kg ‫1-‬ and ketamine 0.5mg kg ‫1-‬ .…”