ROLE OF GLUTATHIONE ON RENAL MITOCHONDRIAL STATUS IN HYPEROXALURIA

Role of glutathione on kidney mitochondrial integrity and function dur ing stone farming process in hyperoxaluric state was investigated in m ale albino rats of Wistar strain. Hyperoxaluria was induced by feeding ethylene glycol (EG) in drinking water. Glutathione was depleted by a dministering buthionine sulfoximine (BSO), a specific inhibitor of glu tathione biosynthesis. Glutathione monoester (GME) was administered fo r supplementing glutathione. BSO treatment alone or along with EG, dep leted mitochondrial GSH by 40% and 51% respectively. Concomitantly, th ere was remarkable elevation in lipid peroxidation and oxidation of pr otein thiols. Mitochondrial oxalate binding was enhanced by 74% and 12 9% in BSO and BSO + EG treatment. Comparatively, EG treatment produced only a 33% increase in mitochondrial oxalate binding. Significant alt eration in calcium homeostasis was seen following BSO and BSO + EG tre atment. This may be due to altered mitochondrial integrity and functio n as evidenced from decreased activities of mitochondrial inner membra ne marker enzymes, succinate dehydrogenase and cytochrome-c-oxidase an d respiratory control ratio and enhanced NADH oxidation by mitochondri a in these two groups. NADH oxidation (r = -0.74) and oxalate depositi on in the kidney (r = -0.70) correlated negatively with mitochondrial glutathione depletion. GME supplementation restored normal level of GS H and maintained mitochondrial integrity and function, as a result of which oxalate deposition was prevented despite hyperoxaluria. These re sults suggest that mitochondrial dysfunction resulting from GSH deplet ion could be a contributing factor in the development of calcium oxala te stones.