Ramipril Blunt Glycerol‐induced Acute Renal Failure in Rats Through its Anti‐apoptosis, Anti‐inflammatory, Anti‐oxidant, and Renin‐inhibiting Properties

Abstract

Acute Kidney Injury (AKI) is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days and causes a buildup of waste products in the blood making it hard for the kidney to keep the right balance of fluid in the body. It affects other organs such as the heart, brain and lungs (Schrier et al., 2004). Renal tubular damage is a pathological characteristic of AKI. 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. Studies have demonstrated that the pathogenesis of glycerol‐induced AKI involves myoglobin toxicity [Gburek et al 2003; Reeder and Wilson 2005], reactive oxygen species (ROS) [Wu et al 2017], inflammation [ Al Asmari et al 2017], apoptosis [Wang et al 2011] and redox‐active iron [Wu et al 2017].In this study ramipril and pioglitazone (reference drug) were evaluated for their potential therapy in glycerol‐induced AKI in rats. 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, NK‐KB, and KIM‐1 were carried out.Results from this study show 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. Histopathologically, there were massive infiltration of leucocytes and congestion of the kidney in toxicant group, but the ramipril treated group showed a milder condition. In immunohistochemistry, the two drugs significantly inhibited the expressions of the four proteins, which were highly expressed in the toxicant group.This study thus showed that ramipril and pioglitazone have nephroprotective effect and thus has ability to blunt acute kidney injury through their anti‐inflammatory, anti‐apoptosis, anti‐renin and anti‐oxidant properties.Support or Funding InformationThis study was supported with a grant (TETFUND/DESS/NRF/UI IBADAN/STI/VOL. 1/B2.20.11) received from the National Research Foundation of the Tertiary Education Trust Fund (TETFUND), Abuja, Nigeria.