Effects of Panthenol and N-Acetylcysteine on Changes in the Redox State of Brain Mitochondria under Oxidative Stress In Vitro

Abstract

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.

Protective Effect of D-Panthenol in Rhabdomyolysis-Induced Acute Kidney Injury

“…D-Panthenol is a derivative of vitamin B5 (pantothenic acid) actively metabolized in mammalian tissues by alcohol dehydrogenase and involved in the biosynthesis of coenzyme A [ 19 , 20 ]. PL is considered to exhibit antioxidant properties, especially by the inhibition of lipid peroxidation in vivo [ 21 , 22 , 23 ] and in vitro on isolated mitochondria [ 15 , 16 ]. It is well known that glycerol-associated rhabdomyolysis is accompanied by a release of myoglobin into the bloodstream followed by its oxidation and a release of iron ions, which could activate the Fenton reaction and lipid peroxidation in the kidneys [ 5 , 6 , 7 ].…”

“…Recently, we have demonstrated that panthenol contributes to the protection of mitochondria through the recovery of energy metabolism, modulation of the redox potential in the glutathione system, and a decrease in the level of S-glutathionylated proteins [ 15 ]. Moreover, panthenol affected oxidative stress, mitochondrial metabolism, and Krebs cycle activity [ 15 , 16 , 17 , 18 ] that all are affected in AKI. The goal of this study was to explore mechanisms of D-panthenol’s impact on AKI in glycerol-induced rhabdomyolysis.…”

Antioxidant Role and Cardiolipin Remodeling by Redox-Activated Mitochondrial Ca2+-Independent Phospholipase A2γ in the Brain

“…The comprehensive and quantitative mapping of the mouse cysteine redox proteome in vivo provided by the database reveals that Cys553 and Cys708 of iPLA 2 γ are oxidized in several tissues, including the brain, suggesting a reversible modification of the respective cysteine residues by hydroperoxides or other electrophiles compatible with oxidizing accessible thiol groups. Coincidentally, a recent study showed that incubation of isolated brain mitochondria with NAC restores the redox state of the glutathione system and increases the levels of S-glutathionylated proteins [ 62 ]. Altogether, the results support our hypothesis that iPLA 2 γ contains cysteine residues accessible to reversible oxidative posttranslational modifications, and oxidation of these residues leads to reversible activation of iPLA 2 γ.…”

COVID-19, Oxidative Stress and Male Reproduction: Possible Role of Antioxidants

“…Owing to its ability to cleave viral disulfide bonds [50], NAC may also help inhibit SARS-CoV-2 invasion into testicular cells. In addition to being a potent anti-inflammatory and antioxidant, NAC maintains the thiol pool, which in turn regulates the redox state as it is an important substrate for glutathione synthesis [51,52]. The anti-inflammatory and antioxidant effects of NAC may contribute to preserving male reproductive functions from COVID-19 mediated damages.…”