The Effects of Modulators of the Coenzyme A Biosynthesis System on Metabolic Stress and the Glutathione System in the CNS in Aluminum Neurotoxicosis

• Published in: Neurochemical journal 2023-03, Vol.17 (1), p.65-74
• Main Authors: Semenovich, D. S., Gurinovich, V. A., Lukienko, E. P., Katkovskaya, I. N., Titko, O. V., Kanunnikova, N. P., Moiseenok, A. G.
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Experimental Articles; Neurosciences
• ISSN: 1819-7124; 1819-7132
• DOI: 10.1134/S181971242301018X

—Alzheimer’s-like disease was simulated in female adult Wistar CRL(WI) WUBR rats by 6-week intragastric administration of aluminum chloride at a dose of 200 mg/kg body mass. In the presence of the developed oxidative stress (OS), we found a decrease in the activities of the tricarboxylic acid cycle (TCA cycle) enzymes and an increase in the activities of the pentose phosphate pathway (PPP) dehydrogenases, as well as a reduction of SH-and SS-groups in proteins along with an increased SH/SS ratio and glutathionylation with simultaneous decreases of glutathione (GSH) and the GSH/GSSG ratio and its redox potential. The glutathione system enzymes were changed multidirectionally, with glutathione reductase remaining stable. Decreased activities of GSH biosynthesis enzymes and cysteine content were noticed. The intragastric administration of the CoA biosynthesis modulators D-panthenol (PL), D-pantethine, or D-homopantothenate (HPA) at a dose of 200 mg/kg from the fifth week of the experiment caused either reduction or leveling of OS manifestations in blood plasma, an increase in acetyl cholinesterase, normalization of the activities of TCA cycle and PPP enzymes and the P-SH level (not the SH/SS ratio), and a significant reduction of S-glutathionylation, as well as increases in the GSH level, the GSH/GSSG ratio and the redox potential in the hemispheres. The effect of CoA system modulators was manifested in activation of glutathione transferase, a decrease of glutathione peroxidase and less evident activation of GSH biosynthesis enzymes (that is, PL) although they contributed to the elevation of the cysteine content due to reduced protein S-cysteinylation. The levels and the ratio of CoA/acetyl-CoA (except for PL) were not changed by toxicosis and the OS modulators. The feasibility of nonconenzyme effects was confirmed by the administration of HPA. The phenomenon of redox activity of the CoA biosynthesis modulators with clearly directional effects on the glutathione system and the TCA cycle and PPP enzymes during alleviation of OS and aluminum neurotoxicosis is discussed.