The role of enzymes of the glyoxalase system in relation to complications in type II diabetes mellitus

Background: Metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. It was considered worthwhile to find out whether changes observed in the levels of glyoxalase I, glyoxalase II, aldose reductase & D-lactate are prognostic indicators for the development of complications of diabetes or merely reflect the result of changes associated with complications.Methods: The glyoxalase system was characterized in erythrocytes of blood samples from patients with type II diabetes mellitus (n=177), and normal healthy control subjects (n=40). Diabetics were divided into 3 main groups based on presence or absence of complications.Results: The concentrations of RBC glyoxalase I, glyoxalase II, aldose reductase, and D-lactate were significantly increased in all groups of diabetic patients, (P <0.001) relative to controls. Comparison between groups showed maximum rise of enzymes in group I and group III (P <0.001); and maximum rise of D-lactate in group III (P <0.001). Within the groups of patients with complications, enzyme levels were markedly increased in patients with IHD/PVD (ischaemic heart disease/peripheral vascular disease) and decreased in patients with nephropathy.  Conclusion: Results of this study suggests a positive relationship between increased activity of erythrocyte enzymes of glyoxalase system and poor or moderate glycemic control. The increased enzyme levels in patients without complications indicate their role as prognostic markers for development of complications. Molecular mechanisms for development of Nephropathy appear to be different from those of Neuropathy and Retinopathy.

Antidepressant activity of Simvastatin in behavioral models of depression in rats

Background: There is evidence, that statins can augment the antidepressant effects of fluoxetine in rats. Hence the present experimental study was designed to evaluate the effect of Simvastatin on duration of immobility in acute forced swim test (Acute FST) and Chronic forced swim test (Chronic FST), as models of behavioral despair in rats.Methods: In acute FST and Chronic FST models, effects of simvastatin (Smv) and fluoxetine (Flx) per se and in combination, on immobility of rats were compared. Open field test was performed to discriminate between the general behavioral stimulation and antidepressant effect of study drugs. Results: In Acute FST, duration of immobility decreased (171.33 ± 6.15 sec) non-significantly in simvastatin group, & decreased significantly in the groups of rats which received fluoxetine alone (161.33 ± 8.68, P < 0.01) or in combination with simvastatin (167.66 ± 7.71 sec, P < 0.001). The 3 treatment groups did not differ from each other. In chronic FST duration of immobility lowered significantly in both, the fluoxetine treated group (147.66 ± 8.73) and the combination treated group (130.5 ± 5.68 sec) with significant fall in the combination group (P < 0.001) compared to the individual therapy groups.Conclusions: Lowering cholesterol levels with statins not only reduces risks for cardiovascular events, but also affect serotonergic neurotransmission, leading to clinical efficacy of standard antidepressants. Simvastatin can augment the antidepressant effects of fluoxetine in rats, raising the possibility that statins could be used to facilitate the effects of antidepressants in humans.