Drug Res (Stuttg) 2020; 70(02/03): 112-118
DOI: 10.1055/a-1085-2542
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Toxicity of Pioglitazone on Mitochondria Isolated from Brain and Heart: An Analysis for Probable Drug-Induced Neurotoxicity and Cardiotoxicity

Enaytollah Seydi
1  Department of Occupational Health and Safety Engineering, Alborz University of Medical Sciences, Karaj, Iran (the Islamic Republic of)
2  Research Center for Health, Safety and Environment, Alborz University of Medical Sciences, Karaj, Iran
,
Tina Servati
3  Department of Pharmacology and Toxicology, Shahid Beheshti University of Medical Science, Tehran, Iran (the Islamic Republic of)
,
Fatemeh Samiei
3  Department of Pharmacology and Toxicology, Shahid Beheshti University of Medical Science, Tehran, Iran (the Islamic Republic of)
,
Parvaneh Naserzadeh
3  Department of Pharmacology and Toxicology, Shahid Beheshti University of Medical Science, Tehran, Iran (the Islamic Republic of)
,
Jalal Pourahmad
3  Department of Pharmacology and Toxicology, Shahid Beheshti University of Medical Science, Tehran, Iran (the Islamic Republic of)
› Author Affiliations
Further Information

Publication History

received 03 November 2019

accepted 16 December 2019

Publication Date:
13 January 2020 (online)

Abstract

Pioglitazone (PG) is one of the thiazolidinedione (TZDs) drugs used in diabetic patients. TZDs are known as peroxisome proliferator-activated receptor gamma (PPARγ) agonists. Mitochondria are considered as one of the targets of these drugs. The mechanisms of the effect of PG on mitochondria are not well understood. In this study, we investigated the effect of PG on mitochondria isolated from brain and heart. Mitochondrial parameters such as succinate dehydrogenase (SDH) activity, reactive oxygen species (ROS) generation, collapse in mitochondrial membrane potential (MMP), mitochondrial swelling and cytochrome c release were evaluated. The results showed that PG at concentrations of 12.5, 25 and 50 µg/ml increased the generation of ROS, the collapse of MMP, mitochondrial swelling and the release of cytochrome c in mitochondria isolated from both brain and heart tissues. The underlying mechanisms of PG induced neuro-toxicity and cardio-toxicity may be associated with changes in mitochondrial function, ROS generation (oxidative stress), and changes in the mitochondrial membrane.