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Rezaiean Mehrabadi A, Jamshidzadeh A, Rashedinia M, et al. Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria. Iran J Pharm Res. 2015;14(3):825-32
Rezaiean Mehrabadi, A., Jamshidzadeh, A., Rashedinia, M., & Niknahad, H. (2015). Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria. Iranian journal of pharmaceutical research : IJPR, 14(3), 825-32.
Rezaiean Mehrabadi, Abbas, et al. "Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria." Iranian journal of pharmaceutical research : IJPR vol. 14,3 (2015): 825-32.
Rezaiean Mehrabadi A, Jamshidzadeh A, Rashedinia M, Niknahad H. Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria. Iran J Pharm Res. 2015;14(3):825-32. PMID: 26330870; PMCID: PMC4518110.
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Iran J Pharm Res. 2015;14(3):825-32.

Study of the Effects of ATP Suppliers and Thiol Reductants on Toxicity of Pioglitazone in Isolated Rat Liver Mitochondria.

Iranian journal of pharmaceutical research : IJPR

Abbas Rezaiean Mehrabadi, Akram Jamshidzadeh, Marzieh Rashedinia, Hossein Niknahad

Affiliations

  1. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

PMID: 26330870 PMCID: PMC4518110

Abstract

Pioglitazone (PG) is one of thiazolidinediones used for the treatment of type II diabetes mellitus. Some reports of its hepatotoxicity exist, but the mechanism of its hepatotoxicity is not well known. In the present study, the protective effect of some ATP suppliers are investigated against mitochondrial toxicity of PG in isolated rat mitochondria. Mitochondrial viability was investigated by MTT assay. The effects of PG on superoxide dismutase activity, ATP production, mitochondrial swelling and oxidative stress were also investigated. PG reduced mitochondrial viability with an LC50 of 880±32 µM. It reduced ATP production and superoxide dismutase activity in mitochondria and increased mitochondrial swelling, but no oxidant effect was present as measured by TBARS formation. Fructose, dihydroxyacetone, dithioteritol, and N-acetylcysteine reduced mitochondrial toxicity of PG. Therefore, PG toxicity may be due to its mitochondrial toxicity and energy depletion, and ATP suppliers could be effective in preventing its toxicity.

Keywords: ATP suppliers; Mitochondria; Pioglitazone; Toxicity

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