Ramipril, an angiotensin-converting enzyme inhibitor ameliorates oxidative stress, inflammation, and hepatic fibrosis in alloxan-induced diabetic rats

Angiotensin-II is considered as a peptide responsible for the vascular dysfunction and complications in various tissues including liver through inducing free radicle mediated oxidative stress. This study aimed to evaluate the effect of ramipril, an angiotensin-converting enzyme inhibitor (ACE inhibitor), on oxidative stress, inflammation, and fibrosis in the liver of alloxan-induced diabetic rats. In this investigation, rats were divided into four groups (six rats in each group): control, control +ramipril, alloxan, and alloxan+ ramipril. A single dose (90 mg/kg) of alloxan was given intra-peritoneally to induce type two diabetes. After the induction of diabetes, ramipril (10 mg/kg) was administered to each animal for 21 days. An oral glucose tolerance test (OGTT) was performed. All animals were sacrificed at the end of the study. Blood and liver tissues were collected from each animal and stored for further biochemical studies. Liver marker enzymes and oxidative stress parameters were also assayed followed by histological examination in the liver. Alloxan administration in rats showed oral glucose intolerance and increased fasting blood glucose levels. Ramipril (10 mg/kg) treatment in alloxan administered rats improved the OGTT and lowered fasting blood glucose level. This study also revealed the elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes activities in the alloxan administered rats which were attenuated by ramipril treatment. Oxidative stress parameters such as advanced protein oxidative products (APOP), nitric oxide (NO), and malondialdehyde (MDA) were also increased in alloxan administered rats which were diminished by the treatment of ramipril. Moreover, alloxan administration increased inflammation and fibrosis in the liver, which was further prevented by ramipril treatment. In conclusion, ramipril alleviated oxidative stress and fibrosis in the liver by suppressing oxidative stress. This investigation suggests that ACE inhibitors may be useful for treating diabetic complications and liver injury in alloxan-administered rats.