Chloroquine Blunts Diabetes Mellitus in Streptozocin‐induced Toxicity in Rats Through Upregulation of Peroxisome Proliferating Activating Receptor‐gamma

Abstract

Although Chloroquine (CQ) has been the cheapest and mainstay treatment for Plasmodium vivax, the development of Chloroquine resistance (CQR) therefore implies that its use in this regards is now limited. Of particular interest to this study are reports linking Chloroquine to insulin and glucose homoeostasis. A significant hypoglycemic effect of Chloroquine has been observed after 3 days in human subjects with non‐insulin‐dependent diabetes mellitus, suggesting that it may be therapeutically useful in type II diabetes (Al‐Bari 2015). It is for the reason that its antidiabetic efficacy is being evaluated in this study. Diabetes mellitus is a very common age‐long chronic disease of humans, and its frontiers are expanding daily. The World Health Organization declared diabetes to be an epidemic condition because about 191 million individual worldwide were afflicted in the year 2000 and a possible increase to 366 million by 2030 was projected (Wild et al., 2004).Diabetes mellitus was induced in rats using streptozocin (50 mg/kg) and after 48 hours, rats with glucose level of 250 mg/dL and above were taken to be diabetic and were used in the study. The study was divided into four groups of five animals per group. Group A comprised of rats that were non‐diabetic and non treated while group B comprised of rats that were diabetic and non‐treated. Group C animals on the other hand were diabetic and treated with pioglitazone (25 mg/kg) while group D animals were treated with 5 mg/kg dose of Chloroquine. Treatment was for 21 days but at day 7, 14 and 21, blood samples were collected for the determination of glucose level. Body weights of the animals were also determined before and after treatment. On day 29, blood samples were collected for serum chemistry. The animals were then sacrificed after which tissues such as liver, kidney, heart and pancreas were collected for histopathology and immunohistochemistry.Results showed that group B animals experienced increase in the levels of oxidative stress markers such as MPO, MDA and hydrogen peroxide whereas reverse is the case for groups C and D animals. Also group B animals experienced decreased levels of enzymic and non‐enzymic antioxidant markers whereas groups C and D experienced increase. There was up regulation of KIM‐1 and cardiac troponin in group B animals while there was a down regulation of these protein in groups C and D animals which also experienced upregulation of PPAR‐gamma and nrf2. With respect to histopathology, there were various levels of necrotic lesions in the kidney, heart and pancreas in group B animals whereas these lesions were mild in groups C and D animals.It could be concluded that Chloroquine exhibited antidiabetic property through upregulation of PPAR‐gamma. Its anti‐inflammatory property was confirmed through the upregulation of nrf2. Its antioxidant property was also exhibited through upregulation of nrf2 and through increase in the levels of the enzymic and non‐enzymic antioxidant markers with corresponding decrease in the levels of oxidative stress markers.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.