Combined effect of probucol and insulin on renal damage in diabetic rats fed a high cholesterol diet.

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on renal damage in streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after streptozotocin administration. Daily treatment with probucol, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals, when histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and mesangial hypertrophy was observed only at 15 weeks). Combined probucol and insulin treatment was the most effective in suppressing these renal histopathological changes. These results indicate that combined treatment with probucol and insulin is useful in preventing the progression of renal damage in diabetic rats. The possible mechanisms for the preventive effect of this combined treatment will be discussed.

Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet.

In the present study, we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin, or their combination on renal damage in streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide (LPO) excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after STZ administration. Daily treatment with vitamin E, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals when histopathological evaluation was performed at 4, 8, and 15 weeks (glomerular and mesangial hypertrophy were observed only at 15 weeks). Combined vitamin E and insulin treatment was the most effective at suppressing these renal histopathological changes. These results indicate that combined vitamin E and insulin treatment additively prevents the development and progression of renal damage in diabetic rats. Possible mechanisms for the preventive effect of this combined treatment are discussed.

Combined effect of probucol and insulin on cataracts of diabetic rats fed a high cholesterol diet.

We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on cataracts of streptozotocin-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after streptozotocin injection. Cataracts were observed from 8 weeks in untreated hypercholesterolemic and diabetic rats and the incidence of catarats increased to 100% by 15 weeks. The incidence of cataracts in rats treated with probucol, insulin and their combination was first seen at 12, 12 and 15 weeks, respectively, and was 86%, 63% and 33%, respectively, at 15 weeks. The preventive effects of both agents alone and their combination on the cataracts were confirmed by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with probucol and insulin is useful in preventing the development and progression of diabetic cataracts.

Combined effect of vitamin E and insulin on cataracts of diabetic rats fed a high cholesterol diet.

In the present study we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin or their combination on cataracts of streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Each rat was checked for cataracts at 0, 1, 2, 4, 8, 12 and 15 weeks after STZ injection. Cataracts were observed from 8 weeks in the control diabetic rats and their incidence of catarats increased to 100% by 12 weeks. The incidence of cataracts in rats treated with vitamin E, insulin and their combination was first seen at 12 weeks and 56%, 20% and 10%, respectively, at 12 weeks and 78%, 50% and 20%, respectively, at 15 weeks. The preventive effects of either agent alone and their combination on the cataracts were in agreement with those obtained by histopathological evaluation of eyeballs. The combined treatment with both agents markedly improved hyperglycemia, hyperlipidemia and increased serum lipid peroxide levels. These results indicate that the combined treatment with vitamin E and insulin is useful in preventing the development and progression of diabetic cataracts.