[The protective effect of pantothenic acid derivatives and changes in the system of acetyl CoA metabolism in acute ethanol poisoning]. / Zashchitnyi éffekt proizvodnykh pantotenovoi kisloty i izmeneniia sistemy metabolizma atsetil-KoA pri ostroi intoksikatsii étanolom.

Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol--ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA-dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism.

[Possible mechanisms of the antitoxic action of calcium-containing derivatives of pantothenic acid in streptomycin poisoning]. / Vozmozhnye mekhanizmy antitoksicheskogo deistviia kal'tsiisoderzhashchikh proizvodnykh pantotenovoi kisloty pri intoksikatsii streptomitsinom.

Calcium salts of pantothenate (CPN), 4'-phosphopantothenate (CPP), S-sulfopantetheine (CSP), as well as pantetheine and panthenol were administered to mice by various routes and the influence of the administration route on acute toxicity of streptomycin (500 mg/kg, subcutaneously) was studied. It was shown that with subcutaneous, intramuscular, intraperitoneal and intravenous administration of CPN, CPP and CSP the acute toxicity of streptomycin was lower. The value of ED50 and the ranges of the antitoxic action (LD50/ED50) were indicative of high efficacy of CPP on its intravenous administration. In rats all the tested compounds normalized the liver excreting function (bromsulphalein test) impaired by exposure to streptomycin in subtoxic doses (200 mg/kg). The lowest levels of acetylation of the sulfacyl sodium test dose were observed in the animals treated with streptomycin in combination with CPN, CPP or CSP which could be explained by increased excretion and acetylation (detoxication) of the antibiotic.

[Antitoxic properties of pantothenic acid derivatives, precursors of coenzyme A biosynthesis, with regard to kanamycin]. / Antitoksicheskie svoistva proizvodnykh pantotenovoi kisloty, predshestvennikov biosinteza kofermenta A v otnoshenii kanamitsina.

The effect of calcium pantothenate (CPN)B 4'-phospho-CPN (PCP), pantetheine (PT) and calcium S-sulfopantetheine (SPN) on acute toxicity of kanamycin sulfate was studied on albino mice. The above derivatives of pantothenic acid except PT lowered the antibiotic toxicity. The coefficient of the antitoxic effect (LD50/ED50) of SPN and PCP was 1.3-1.4 times higher than that of CPN. The combined use of kanamycin (1/5 of the LD50) with CPN, PCP or PT (30 mg/kg bw was equivalent to CPN) for 15 days prevented the increase in the total content of CoA and in the content of the fraction of free CoA and the precursors of its biosynthesis participating in the reaction of N-acetylation in the liver and brain. The contents of these substances were within the normal during the whole experiment. A certain increase in the activity of pantothenate kinase in the liver cytosol due to the use of kanamycin was eliminated by the simultaneous use of PCP and PT. The vitamin-containing compounds PCP and SPN were recommended for the clinical trials as agents preventing complications of kanamycin therapy.