Toxicological evaluation of subchronic use of pioglitazone in mice

Objective(s): Pioglitazone (Actos) is one of the most controversial recent oral antidiabetic drugs. It was originally authorized in the European Union in ۲۰۰۰, and approved as an oral monotherapy for overweight second type of diabetic patients in ۲۰۰۲. It belongs to the thiazolidinedione group which some of its members have been withdrawn from the market due to the hepatotoxicity or cardiotoxicity effects.This studyinvestigates sub-chronic use of pioglitazone induced toxicity in mice by the assessment of renal and liver function tests, cardiac enzymes, and some hematological indices with histological changes of liver, kidney, heart, and bladder. Materials and Methods: ۱۲۰ albino mice were divided into four groups; ۳۰ in each. The first group (control) received water, second (diabetic) group received alloxan only, while the third and the fourth groups received alloxan with ۲۰۰ and ۴۰۰ mg/kg/day of pioglitazone, respectively for ۹۰ days. Results: Prolonged use of pioglitazone induced significant abnormalities of hepatic, renal, and cardiac biomarkers and some hematological indices associated with histopathological changes in the liver, kidney, heart, and bladder that increased based on administered dose. Conclusion: Subchronic use of pioglitazone leads to hepatic, renal, cardiac, hematological, and bladder affection depending on the applied dose.

کلیدواژه ها:

Mice ، Pioglitazone ، Sub-chronic use ، Toxicity