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Protective Effects of Alpha Lipoic Acid Against Arsenic Induced Oxidative Stress in Isolated Rat Liver Mitochondria

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Abstract

Arsenic as a heavy metal and toxic pollutant has been established that has the hepatotoxic effect in animal and human models. Previous studies showed that mitochondria as the first target of arsenic toxicity has a pathogenic role in liver diseases. This study investigated alpha lipoic acid (ALA) as an antioxidant could ameliorate against liver toxicity induced by arsenic in rat mitochondria. First, mitochondria were isolated by the liver tissue centrifugation protocol. Then, isolated mitochondria were exposed with different concentrations of ALA and arsenic in different times for receiving the optimum dose and time. Finally, mitochondria were pretreated with the optimum concentrations and times of ALA and then treated with optimum concentration and time of arsenic (160 μg/ml; 30 min). The results demonstrated a significant decrease in total mitochondrial dehydrogenase activity (mitochondrial complex II) by 3, 4 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay after arsenic exposure. Mitochondria treated with arsenic also showed a significant increase in ROS generation, MMP, and MDA levels. The activity of mitochondrial catalase and mitochondrial GSH significantly decreased after exposure of mitochondria with arsenic. Pretreatment of mitochondria with ALA improved mitochondrial complex II activity; decreased mitochondrial membrane damage, MDA, and ROS amounts; and ameliorated mitochondrial GSH levels and mitochondrial catalase activity. These findings revealed that arsenic induced oxidative stress and mitochondria dysfunction, while ALA improved mitochondrial function through increasing of antioxidant defense or preserving of complex II, but suggested that ALA could prevent from mitochondria dysfunction.

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Abbreviations

DTNB:

Dithiobis-2-nitrobenzoic acid

EDTA:

Ethylene diamine tetra acetic acid

DCFH-DA:

Dichlorofluorescein diacetate sucrose

Rh 123:

Rhodamine 123

DMSO:

Dimethyl sulfoxide

HEPES:

Hydroxyethyl piperazineethanesulfonic acid

TBA:

Thiobarbituric acid

TCA:

Tri chloro acetic acid

ALA:

Alpha lipoic acid

MMP:

Mitochondrial membrane damage

MDA:

Malondialdehyde

GSH:

Glutathione

ROS:

Reactive oxygen species

TAC:

Total antioxidant capacity

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Acknowledgements

This article is extracted from Farzan Mozaffarian thesis with registration no. B-97046 for a Pharm. D degree of Ahvaz Jundishapur University of Medical Sciences.

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Authors and Affiliations

  1. Toxicology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Farzan Mozaffarian, Mohammad Amin Dehghani, Atefeh Raesi Vanani & Masoud Mahdavinia

  2. Department of Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran

    Farzan Mozaffarian, Mohammad Amin Dehghani, Atefeh Raesi Vanani & Masoud Mahdavinia

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  1. Farzan Mozaffarian
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  2. Mohammad Amin Dehghani
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  3. Atefeh Raesi Vanani
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  4. Masoud Mahdavinia
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Correspondence to Masoud Mahdavinia.

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Mozaffarian, F., Dehghani, M.A., Vanani, A.R. et al. Protective Effects of Alpha Lipoic Acid Against Arsenic Induced Oxidative Stress in Isolated Rat Liver Mitochondria. Biol Trace Elem Res 200, 1190–1200 (2022). https://doi.org/10.1007/s12011-021-02712-3

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