Effects of Exercise and Alpha-Lipoic Acid Supplementation in Diabetes

Açıklama

The present thesis aims to clarify the effects of exercise training and thiol supplementation (lipoic acid, LA) on exercise-induced oxidative stress and protection, including endogenous antioxidant homeostasis and heat shock proteins (HSPs) in diabetic and non-diabetic rat brain. Protection against oxidative stress, a disruption of redox control of signalling and cellular events, depends on an orchestrated synergism between several exogenous macronutrients and endogenous antioxidants. Exercise-induced oxidative stress stimulates antioxidant protection, which can be also prolonged, and may manifest a sustained response during exercise training.
Physical exercise induces HSPs, which have a central role in protein homeostasis and protection in various tissues predominantly skeletal muscle, the effect of exercise on brain is limited. Experimental diabetes model in rat brain was used. At baseline, HSP levels, TRX-1 protein, activity and levels of thioredoxin-interacting protein(TXNip), an endogenous inhibitor of TRX were not different between SID and non-diabetic animals. Training or diabetes had no effect on protein carbonyl content and oxidative markers. On the contrary, the proportion of oxidized glutathione (GSSG) to total GSH was increased in diabetic animals, indicating increased oxidative stress. The levels of elongation factor eEF-1 and eEF-2 kinase were not affected by diabetes or endurance training.
Exercise training increased TRX-1 protein levels in brain, but diabetes down regulated the TRX response to exercise training and induced TXNip. Thus, the beneficial effects of physical exercise on the TRX system were inhibited by diabetes. Similarly, endurance training increased HSP expression in brain tissue, and experimental diabetes impaired the HSP response at the protein level. Exhaustive exerciseinduced mRNA of TRX-1 in the brain. LA supplementation did not prevent diabetes-induced disturbances in GSH
and TRX homeostasis; in contrast, LA supplementation increased TXNip transcription.
Moreover, LA supplementation increased HSC70mRNA expression in diabetic animals, but decreased expression in non-diabetic controls. On the other hand, LA supplementation had no effect on the levels of any of the proteins analysed. Based on this study, brain antioxidant status and redox regulation can be improved in a safe and physiological manner using physical exercise, which may provide a means for improving brain health. However, LA supplementation had no beneficial effects on brain protection.