Management of metabolic disorders: Diabetes mellitus (mainly the secondary complications of the disease)  

Nephropathy or kidney disease is one of the dangerous secondary complications induced by diabetes. In an animal model study, it was observed that dietary curcumin brought about significant inhibition in the progression of renal lesions. Curcumin fed at 0.5% level in the diet to streptozotocin-induced diabetic rats for eight weeks lessened renal damage and preserved the integrity and functions of the kidneys. Kidney damage was assessed by the amount of proteins excreted in the urine and the extent of leaching of renal tubular enzymes. The integrity of the kidney was assessed by measuring the activities of several key enzymes of the kidney tissues including glucose-6-phosphatase, lactic dehydrogenase, ATPases and other enzymes which are normally active in the various metabolic pathways (carbohydrate metabolism, polyol pathway). Membrane integrity was assessed by determining the ratio PUFA/SFA (Polyunsaturated fatty acids to saturated fatty acids). The results were corroborated by histological examination of the relevant sections of the kidneys. The authors inferred that the beneficial effects of dietary curcumin on diabetic nephropathy is probably mediated through the hypolipidemic effects of curcumin.

Age-related cataractogenesis is a significant health problem worldwide and is also commonly found in diabetics. Oxidative stress has been suggested to be a common underlying mechanism of the formation of cataracts. If the antioxidant defenses of the ocular lens is enhanced, the formation of cataracts is delayed or prevented. A study was designed to test the efficacy in preventing cataractogenesis in an in vitro rat model. Rats were maintained on a standard diet for 2 weeks, after which they were given a daily dose of corn oil alone or with 75 mg curcumin/kg body weight in corn oil for 14 days. Their lenses were removed and cultured for 72 hours in vitro in the presence or absence of 100 microM of 4-hydroxy-2-nonenal, which is a highly electrophilic product of lipid peroxidation. The results of these studies showed that 4-HNE caused cultured lenses to become opaque, as indicated by the measurements of transmitted light intensity. However, the lenses from curcumin-treated rats were much more resistant to 4-HNE-induced opacification than were lenses from control animals fed curcumin-free diet. Curcumin treatment was found to cause a significant induction of the glutathione S-transferase (GST) isozyme rGST8-8 in rat lens epithelium. This enzyme is known to preferentially utilize 4-HNE. The authors suggest that the protective effect of curcumin may be mediated through the induction of this GST isozyme and that curcumin may be an effective protective agent against cataract formation induced by lipid peroxidation.

Increased oxidative stress and high serum glucose levels have been postulated to contribute significantly to the accelerated accumulation of advanced glycation end products (AGEs) in diabetics. This results in cross-linking of collagen and the progression of the degenerative secondary complications of diabetes. Curcumin (200 mg/kg body wt, administered orally) was found to reduce the level of AGEs and the cross-linking of collagen in diabetic rats. The oxidative stress in diabetic rats was observed to reduce significantly on curcumin administration. Similarly, the accumulation of lipid peroxidation products in serum of diabetic rats was reduced significantly by curcumin. Accelerated accumulation of AGE-collagen and extensive cross-linking of collagen in the tail tendon and skin of diabetic animals was also prevented to a greater extent by curcumin treatment. The preventive effect of curcumin on the advanced glycation and cross-linking of collagen was more pronounced than its therapeutic effect. This study confirmed the significance of free radicals in the accumulation of AGEs and cross-linking of collagen in diabetes and validated the use of curcumin for the inhibition of AGE-induced complications of diabetes mellitus.

Hyperlipidemia is often associated with diabetes and could induce cardiovascular problems. In earlier studies, curcumin was proven to be an effective hypolipidemic agent 82. One study validated the role of dietary curcumin in maintaining healthy serum cholesterol levels in diabetic rats. Streptozotocin-induced diabetic rats were maintained on 0.5% curcumin containing diet for 8 weeks. It was observed that the LDL-VLDL fraction and the serum levels of triglycerides and phospholipids were reduced by dietary curcumin in diabetic rats. In a parallel study employing a high cholesterol diet for the diabetic rats, curcumin exhibited lowering of cholesterol and phospholipid in treated animals as compared to curcumin-free controls. Liver cholesterol, triglycerides and phospholipid elevated under diabetic conditions were lowered by dietary curcumin, in both studies. Renal cholesterol and triglycerides elevated in diabetic rats, were similarly lowered by the curcumin in the diet. The authors observed that the enzyme activity of liver cholesterol-7a-hydroxylase was markedly higher in curcumin fed diabetic animals. This suggests that curcumin induces a higher rate of cholesterol catabolism.


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