Ramipril mitigates Glycerol-induced Acute Kidney Injury in Rats via its Anti-oxidant, Anti-renin and Anti-apoptosis Effects.

A sudden decrease in the functionality of the kidney with concomitant structural damage and functional loss is known as acute kidney injury (AKI), with some of the potential causes having to do with a focal mismatch between oxygen and nutrient delivery to the nephrons. Increased energy demands on account of cellular stress is another cause [Kellum et al 2021]. AKI occurs when renal function is acutely decreased, so waste products accumulate within the body, making the body unable to maintain electrolyte, acid-base, and water balance [Bhatraju et al 2020]. As a result of the decrease in the kidney's ability to carry out its perfusion activity, the epithelial cells lost the ability to maintain sufficient intracellular ATP for essential processes. This ATP depletion leads to cell injury. Depending on the severity of ATP depletion, cell death by necrosis or apoptosis could occur [Biswas et al 2018]. Studies have actually demonstrated that the pathogenesis of glycerol-induced AKI involves myoglobin toxicity, reactive oxygen species, inflammation, and redox-active iron [Al Asmari et al 2017; Wu et al 2017]. Currently, animal models of glycerol-induced AKI are widely used [Mousleh et al 2018]. Glycerol injection into the muscle causes the release of myoglobin and other muscle contents into the circulation, ultimately resulting in AKI. Twenty animals divided into four groups of five animals per group were used. Group I served as control while group II received glycerol on day 8 only. Groups III and IV were administered with pioglitazone and ramipril for 7 days respectively and on day 8 received glycerol. On day 9 blood samples were collected for serum biochemical analysis of markers of oxidative stress, enzymatic and non-enzymatic antioxidants, creatinine and blood urea nitrogen. Animals were sacrificed thereafter; and kidney tissues were harvested for histopathology and immunohistochemistry. Expression of caspase 3, renin receptor, NF-κB, and KIM-1 were carried out. Results from this study showed that ramipril and pioglitazone significantly inhibited markers of oxidative stress while also significantly increased the levels of enzymatic and non-enzymatic anti-oxidant markers. These drugs caused decreased levels of creatinine and BUN. While massive leucocytes infiltration and congestion of the kidney occurred in the toxicant group, it was mild in the ramipril treated group and the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group. Thus ramipril and pioglitazone have nephroprotective effect and mitigated acute kidney injury through their anti-inflammatory, anti-apoptosis, anti-renin and anti-oxidant properties. Some References Al Asmari AK, Al Sadoon KT, Obaid AA, Yesunayagam D, Tariq M. Protective effect of quinacrine against glycerol-induced acute kidney injury in rats. BMC Nephrol. 2017; 18:41. Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Hans- Joachim A. Acute kidney injury. Disease Primers 2021; 7: 52.