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.

—We studied changes in the indices of free-radical oxidation and thiol-disulfide status in the brain structures in the experimental model of Parkinson’s disease (PD) induced by administration of rotenone to rats. Pantothenic acid derivatives, such as panthenol (PL), pantethine (PT), and homopantothenic acid (HPA) were used as neuromodulators. It was found that redox imbalance in the brain induced by rotenone is accompanied by the activation of free-radical processes, pronounced inhibition of antioxidant defense, a considerable decrease in the glutathione system reduction potential, and increased protein glutathionylation. The strongest changes were in the basal ganglia of the brain. PL and PT but not HPA, decrease the changes in the free-radical oxidation and thiol-disulfide balance in the brain structures. During experimental neurotoxicosis, the mechanisms of neuroprotective action of PL and PT, which are linked with the changes in the biosynthesis of CoA, are, obviously, related to their ability to increase the reduction potential of the glutathione system, thus mitigating the effects of oxidative stress.

We studied the effects of the glycyl-proline dipeptide (Gly-Pro) at a dose of 3 mg/kg on the contents of neuroactive amino acids, including aspartate, glycine, alanine, taurine, GABA, and glutamate, the activity of the enzymes of the GABA shunt, such as GABA-transaminase, succinic semialdehyde dehydrogenase, and glutamate decarboxylase, and enzymes of glutamate metabolism, such as glutamate dehydrogenase and alanine and aspartate transaminases in the neocortex of rats subjected to 6-h brain ischemia. We used three means of dipeptide administration, including intraperitoneal, subconjunctival, and intranasal. We found that the protective anti-ischemic effect of Gly-Pro was mostly expressed after intranasal administration.