Pyridoxamine, an inhibitor of protein glycation, in relation to microalbuminuria and proinflammatory cytokines in experimental diabetic nephropathy.

Diabetic nephropathy (DN) is one of the major complications that develop as consequence of chronic and uncontrolled hyperglycaemia. Hyperglycaemia initiates various processes, one of which is protein glycation, leading to the formation of advanced glycation end products. Alteration of intracellular signalling, gene expression, release of proinflammatory molecules and free radicals are examples of such changes and they contribute to the initiation of diabetic complications. In the current manuscript, we studied the effect of pyridoxamine (PM) on protein glycation, oxidative stress, interleukin-1α (IL-1α), IL-6, C-reactive protein (CRP), gene expression of tumour necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1) in relation to microalbuminuria and kidney functions in a model of alloxan-induced diabetic rats. We have observed that onset of microalbuminuria has preceded the gradual increase of blood sugar level in diabetic rats. In diabetic rats, gene expression of TNF-α and TGF-β1 recorded a gradual increase and marked increase was observed after one and two weeks of alloxan administration, in comparison with normal rats. PM induced significant decrease in kidney malondialdehyde content and the gene expression of TNF-α and TGF-β1, in addition to levels of serum glucose, fructosamine, urea, creatinine, IL-1α, IL-6, CRP and urine microalbumin. Histopathological examination of kidney tissues showed certain improvements as compared with diabetic control. In conclusion, our results may provide a supporting evidence for the therapeutic benefit of PM in DN.