The therapeutic potential of
lipoic acid (LA) in diabetes and
diabetic nephropathy treatment was elucidated.
Alloxan diabetic rabbits were treated daily for three weeks with either 10 or 50 mg of LA per kg
body weight (i.p.). The following parameters were measured: 1) serum
glucose,
urea,
creatinine and
hydroxyl free radical (HFR) levels; 2) blood
glutathione redox state; 3) urine
albumin concentration; 4) hepatic and renal HFR levels, GSH/
GSSG ratios,
cysteine contents and the activities of the
enzymes of
glutathione metabolism; and 5) the activity of renal
NADPH oxidase. Histological studies of kidneys were also performed. The treatment of diabetic rabbits with 50 mg of LA resulted in lethal hypoglycaemia in 50% of animals studied. Although the low dose of LA did not change serum
glucose concentration, it decreased serum
urea and
creatinine concentrations, attenuated diabetes-induced decline in GSH/
GSSG ratio and abolished
hydroxyl free radicals accumulation in serum, liver and kidney cortex. LA did not change the activities of the
enzymes of
glutathione metabolism, but it elevated hepatic content of
cysteine, which limits the rate of
glutathione biosynthesis. Moreover, LA lowered urine
albumin concentration and attenuated glomerulopathy characteristic of diabetes. However, it did not affect diabetes-stimulated activity of renal
NADPH oxidase. In view of these data, it is concluded that low doses of LA might be useful for the
therapy of diabetes and
diabetic nephropathy. Beneficial action of LA seems to result mainly from direct scavenging of HFR and restoring
glutathione redox state due to elevation of intracellular
cysteine levels.