The glutathione system in the mitochondria of the brain plays an important role in maintaining the redox balance and thiol–disulfide homeostasis, whose violations are the important component of the biochemical shifts in neurodegenerative diseases. Mitochondrial dysfunction is known to be accompanied by the activation of free radical processes, changes in energy metabolism, and is involved in the induction of apoptotic signals. The formation of disulfide bonds is a leading factor in the folding and maintenance of the three-dimensional conformation of many specific proteins that selectively accumulate in brain structures during neurodegenerative pathology. In this study, we estimated brain mitochondria redox status and functioning during induction of oxidative damage in vitro. We have shown that the development of oxidative stress in vitro is accompanied by inhibition of energy metabolism in the brain mitochondria, a shift in the redox potential of the glutathione system to the oxidized side, and activation of S-glutathionylation of proteins. Moreover, we studied the effects of pantothenic acid derivatives—precursors of coenzyme A (CoA), primarily D-panthenol, that exhibit high neuroprotective activity in experimental models of neurodegeneration. Panthenol contributes to the significant restoration of the activity of enzymes of mitochondrial energy metabolism, normalization of the redox potential of the glutathione system, and a decrease in the level of S-glutathionylated proteins in brain mitochondria. The addition of succinate and glutathione precursor N-acetylcysteine enhances the protective effects of the drug.

We investigated the nephroprotective effect of D-panthenol in rhabdomyolysis-induced acute kidney injury (AKI). Adult male Wistar rats were injected with 50% glycerol solution to induce rhabdomyolysis. Animals with rhabdomyolysis were injected with D-panthenol (200 mg/kg) for 7 days. On day 8, we examined AKI markers, renal histology, antioxidant capacity, and protein glutathionylation in kidneys to uncover mechanisms of D-panthenol effects. Rhabdomyolysis kidneys were shown to have pathomorphological alterations (mononuclear infiltration, dilatation of tubules, and hyaline casts in Henle’s loops and collecting ducts). Activities of skeletal muscle damage markers (creatine kinase and lactate dehydrogenase) increased, myoglobinuria was observed, and creatinine, BUN, and pantetheinase activity in serum and urine rose. Signs of oxidative stress in the kidney tissue of rhabdomyolysis rats, increased levels of lipid peroxidation products, and activities of antioxidant enzymes (SOD, catalase, and glutathione peroxidase) were all alleviated by administration of D-panthenol. Its application improved kidney morphology and decreased AKI markers. Mechanisms of D-panthenol’s beneficial effects were associated with an increase in total coenzyme A levels, activity of Krebs cycle enzymes, and attenuation of protein glutathionylation. D-Panthenol protects kidneys from rhabdomyolysis-induced AKI through antioxidant effects, normalization of mitochondrial metabolism, and modulation of glutathione-dependent signaling.

The changes in the parameters of oxidative stress, energy metabolism, and redox potential of the glutathione system in the rat brain following cerebral ischemia were studied. To correct metabolic disorders, the pantothenic acid derivatives were used in combination with precursors of glutathione biosynthesis and selenium substances.Cerebral ischemia was modeled by ligating the both common carotid arteries in rats for 2 h. Drugs were administered i.p. in the following doses: panthenol – 400 mg/kg, N-acetylcysteine – 150, nanoselen – 1 mg/kg, three times: 1 h before ligation of the carotid arteries, at the time of ligation and 1 hour after ligation. We showed that the development of oxidative stress caused by ischemia is accompanied by the changes in the parameters of energy metabolism and the pentose phosphate pathway in the cerebral hemispheres. Simultaneously, there are a decrease in the GSH level, an increase in the GSSG content, a decrease in the GSH/GSSG ratio, and the activation of enzymes of redox transformations of glutathione.The redox potential of the glutathione system decreases and shifts towards oxidation, while the level of S-glutathionylated proteins increases. Thus, the value of the GSH/GSSG ratio and the protein glutathionylation intensity are the sensitive indicators of the redox potential in the brain tissue and can be used as markers of the extent of changes in the redox balance. The panthenol injection to animals leads to a decrease in the content of free radical oxidation products, violations of oxidative phosphorylation and restoration of thiol-disulfide balance in the brain. When panthenol is administered together with N-acetylcysteine and nanoselen, the corrective effect of panthenol is enhanced.