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troglitazone and rosiglitazone, were withdrawn from the market because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.