A. Muthukumar et R. Selvam, ROLE OF GLUTATHIONE ON RENAL MITOCHONDRIAL STATUS IN HYPEROXALURIA, Molecular and cellular biochemistry, 185(1-2), 1998, pp. 77-84
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.