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Role of glutathione on renal mitochondrial status in hyperoxaluria

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Abstract

Role of glutathione on kidney mitochondrial integrity and function during stone forming process in hyperoxaluric state was investigated in male albino rats of Wistar strain. Hyperoxaluria was induced by feeding ethylene glycol (EG) in drinking water. Glutathione was depleted by administering buthionine sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis. Glutathione monoester (GME) was administered for supplementing glutathione. BSO treatment alone or along with EG, depleted mitochondrial GSH by 40% and 51% respectively. Concomitantly, there was remarkable elevation in lipid peroxidation and oxidation of protein thiols. Mitochondrial oxalate binding was enhanced by 74% and 129% in BSO and BSO + EG treatment. Comparatively, EG treatment produced only a 33% increase in mitochondrial oxalate binding. Significant alteration in calcium homeostasis was seen following BSO and BSO + EG treatment. This may be due to altered mitochondrial integrity and function as evidenced from decreased activities of mitochondrial inner membrane marker enzymes, succinate dehydrogenase and cytochrome-c-oxidase and respiratory control ratio and enhanced NADH oxidation by mitochondria in these two groups. NADH oxidation (r = -0.74) and oxalate deposition in the kidney (r = -0.70) correlated negatively with mitochondrial glutathione depletion. GME supplementation restored normal level of GSH and maintained mitochondrial integrity and function, as a result of which oxalate deposition was prevented despite hyperoxaluria. These results suggest that mitochondrial dysfunction resulting from GSH depletion could be a contributing factor in the development of calcium oxalate stones.

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Authors and Affiliations

  1. Virology Section, Department of Microbiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India

    Alagarraju Muthukumar

  2. Department of Biochemistry, Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Madras, India

    Ramasamy Selvam

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  1. Alagarraju Muthukumar
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  2. Ramasamy Selvam
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Muthukumar, A., Selvam, R. Role of glutathione on renal mitochondrial status in hyperoxaluria. Mol Cell Biochem 185, 77–84 (1998). https://doi.org/10.1023/A:1006817319876

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