Introduction

Pioglitazone, an oral antidiabetic agent in thiazolidinedione group, was first introduced in 2000 as a single dose per day use. Then, in 2002, it was also approved for use in oral monotherapy for overweighed diabetic patients whose blood sugar could not be controlled by diet and exercise (1). Thiazolidinediones, also called peroxisome proliferating activating receptor gamma (PPAR-γ) agonists, exert their effects mainly by the activation of these receptors. Thiazolidinediones, which provide glycemic control by improving insulin sensitivity, are lipophilic and can enter to the cell nucleus and bind to PPAR-γ (2). Thiazolidinediones also increase transcription of insulin-sensitive genes by targeting nuclear PPAR-γ (3). The active substance pioglitazone is used frequently today either alone or in combination with other drugs (4). Other thiazolidinediones, troglitazone and rosiglitazone, were withdrawn from the market because of their hepatotoxic and cardiotoxic effects (4–6). The most important side effects of pioglitazone are heart failure and peripheral edema. The congestion caused by pioglitazone is resistant to diuretic therapy (7). Ventricular hypertrophy, congestion of kidney and liver tissues, deterioration of liver and cardiac enzymes have been demonstrated in animal model studies on pioglitazone intoxication (8,9). Because it lowers blood glucose by improving target cell response to insulin, and without increasing pancreatic insulin secretion, it is highly preferred for obesity control by the physicians besides antidiabetic effects. It is an easy-to-find and frequently used drug, therefore intoxications with pioglitazone alone or in combination with other drugs are not rare (10,11). However, to our knowledge in the literature there are no studies about the reversibility and treatability of the toxic effects of pioglitazone. Supportive treatment modalities are advised to use in the management of overdose cases. Intralipid emulsions (ILE) are present in the form of medium chain triglycerides, long chain triglycerides or combinations thereof. They are primarily used for nutritional support. The effects of intralipid emulsion treatment in poisoning cases were first tested in cardiac arrest models studied with bupivacaine, a local anesthetic, in animals (12). Then, with the positive results reported consecutively, it was recommended to be used in humans if cardiac arrest developed due to local anesthetic poisoning (13). Finally, the researchers focused on the effectiveness of ILE as a rescue agent in other lipophilic drug intoxications (12,14,15). American Heart Association declared in 2015 guidelines that it may be reasonable to administer ILE to patients with other forms of drug toxicity who are failing to recover from standard resuscitative measures (13). In this study, the histopathologic effects of pioglitazone which is a lipophilic drug and changes due to acute poisoning on tissues were investigated (2). Also, the effectiveness of ILE in reversing these possible unwanted effects was tested in a rat model.