The Antidiabetic Potential of Chloroquine in Streptozotocin-Induced Diabetes and its Complications in Rats

Abstract

This study assessed the therapeutic effects of chloroquine on diabetes and its renal, cardiac and hepatic complications. A single intraperitoneal streptozotocin (STZ) injection in an animal model was used for this study. Blood glucose level, body weight, markers of oxidative stress such as malondialdehyde (MDA), hydrogen peroxide (H2O2) generation, protein carbonyl, nitric oxide (NO), reduced glutathione and antioxidant enzymes such as superoxide dismutase, glutathione peroxidase were evaluated. Histopathology of various organs was done to evaluate structural changes. Immunohistochemical changes using CTnI, Kim-1, PPARγ and Nrf2 were also performed. It was shown that chloroquine administration significantly improved blood glucose levels and body weight. Structural changes such as necrosis, inflammatory cell infiltration, and congestion induced by STZ injection were ameliorated with chloroquine treatment. Untreated diabetic animals showed marked increase in levels of oxidative stress and inflammatory markers such as MDA, H2O2, NO, MPO, and depletion in both non-enzymatic and enzymatic antioxidant defense system, upregulation of Kim1, CTnI, downregulation of PPARγ and Nrf2. Treatment with chloroquine ameliorated renal and cardiac injury coupled with increased expressions of Kim-1 and CTnI. It can therefore be postulated that chloroquine exhibited antidiabetic property through upregulation of PPARγ. Its anti-inflammatory and antioxidant properties were confirmed through the upregulation of Nrf2 and improved antioxidant status.