Acute Pioglitazone Intoxication in Rats: Lack of Protective Effect of Intravenous Lipid Emulsion-A Pilot Study.

Abstract

Intravenous lipid emulsion (ILE) is an established antidote for local anesthetic systemic toxicity and has been tested in various lipophilic drug intoxications, but its efficacy in pioglitazone toxicity remains unclear. This study evaluated the biochemical and histopathological effects of pioglitazone and the potential protective role of ILE in an animal model. Thirty-two male Sprague-Dawley rats were randomly assigned to four groups (n = 8): control, ILE (12.4 mL/kg, 20% IV), pioglitazone (PIO; ½ LD₅₀, 1000 mg/kg), and PIO + ILE. ILE (or saline) was administered intravenously over ~2 min immediately after pioglitazone, with matched volume and duration. Animals were observed for 24 h with free access to food and water. At 24 h, rats were decapitated, and blood and tissue samples were analyzed. Pioglitazone induced significant hepatic and renal injury (both p < 0.001), while cardiac changes were minimal and nonsignificant. ILE administration did not reduce liver or kidney injury. The ILE-only group showed higher renal injury versus controls (p < 0.001). Serum biochemistry revealed increased BUN and creatinine in PIO + ILE compared with Control and ILE (adjusted p < 0.05), with no difference between PIO and PIO + ILE. ILE failed to reverse hepatic or renal injury in acute pioglitazone toxicity and was associated with potential nephrotoxic effects. These findings suggest limited utility of ILE for pioglitazone overdose, likely reflecting drug physicochemical properties (moderate lipophilicity and high protein binding) and timing/dosing constraints. Caution is warranted, particularly regarding renal effects.