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Protective effects of N-acetylcysteine against hyperoxaluria induced mitochondrial dysfunction in male wistar rats

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Abstract

The purpose of the present study was to evaluate the nephro-protective potential of N-acetylcysteine against hyperoxaluria-induced renal mitochondrial dysfunction in rats. Nine days dosing of 0.4 % ethylene glycol +1 % ammonium chloride, developed hyperoxaluria in male wistar rats which resulted in renal injury and dysfunction as supported by increased level of urinary lactate dehydrogenase, calcium, and decreased creatinine clearance. Mitochondrial oxidative strain in hyperoxaluric animals was evident by decreased levels of superoxide dismutase, glutathione peroxidase, glutathione reductase, reduced glutathione, and an increased lipid peroxidation. Declined activities of respiratory chain enzymes and tricarboxylic acid cycle enzymes showed mitochondrial dysfunction in hyperoxaluric animals. N-acetylcysteine (50 mg/kg, i.p.), by virtue of its –SH reviving power, was able to increase the glutathione levels and thus decrease the oxidative stress in renal mitochondria. Hence, mitochondrial damage is, evidently, an essential event in ethylene glycol-induced hyperoxaluria and N-acetylcysteine presented itself as a safe and effective remedy in combating nephrolithiasis.

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Abbreviations

COM:

Calcium oxalate monohydrate

DTNB:

5,5-Dithiobis-2-nitrobenzoic acid

EG:

Ethylene glycol

ETC:

Electron transport chain

GR:

Glutathione reductase

GSH:

Reduced glutathione

GPx:

Glutathione peroxidase

i.p.:

Intraperitoneal

LDH:

Lactate dehydrogenase

LPO:

Lipid peroxidation

NP-SH:

Non-protein thiols

MDA:

Malondialdehyde

Mn-SOD:

Manganese superoxide dismutase

NADH:

Nicotinamide adenine dinucleotide

NAC:

N-acetylcysteine

ROS:

Reactive oxygen species

T-SH:

Total thiols

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Acknowledgments

The financial assistance provided by the University Grants Commission, New Delhi is gratefully acknowledged.

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The authors state no conflict of interest.

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Correspondence to S. K. Singla.

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Sharma, M., Kaur, T. & Singla, S.K. Protective effects of N-acetylcysteine against hyperoxaluria induced mitochondrial dysfunction in male wistar rats. Mol Cell Biochem 405, 105–114 (2015). https://doi.org/10.1007/s11010-015-2402-6

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