Protection by pantothenol and beta-carotene against liver damage produced by low-dose gamma radiation.

Rats were exposed to a total dose of 0.75 Gy of gamma radiation from a 60Co source, receiving three doses of 0.25 Gy at weekly intervals. During two days before each irradiation, the animals received daily intragastric doses of 26 mg pantothenol or 15 mg beta-carotene per kg body mass. The animals were killed after the third irradiation session, and their blood and livers were analyzed. As found previously (Slyshenkov, V.S., Omelyanchik, S.N., Moiseenok, A.G., Trebukhina, R.V. & Wojtczak, L. (1998) Free Radical Biol. Med. 24, 894-899), in livers of animals not supplied with either pantothenol or beta-carotene and killed one hour after the irradiation, a large accumulation of lipid peroxidation products, as conjugated dienes, ketotrienes and thiobarbituric acid-reactive substances, could be observed. The contents of CoA, pantothenic acid, total phospholipids, total glutathione and GSH/GSSG ratio were considerably decreased, whereas the NAD/NADH ratio was increased. All these effects were alleviated in animals supplied with beta-carotene and were completely abolished in animals supplied with pantothenol. In the present paper, we extended our observations of irradiation effects over a period of up to 7 days after the last irradiation session. We found that most of these changes, with the exception of GSH/GSSG ratio, disappeared spontaneously, whereas supplementation with beta-carotene shortened the time required for the normalization of biochemical parameters. In addition, we found that the activities of glutathione reductase, glutathione peroxidase, catalase and NADP-dependent malate (decarboxylating) dehydrogenase ('malic enzyme') in liver were also significantly decreased one hour after irradiation but returned to the normal level within 7 days. Little or no decrease in these activities, already 1 h after the irradiation, could be seen in animals supplemented with either beta-carotene or pantothenol. It is concluded that pantothenol is an excellent radioprotective agent against low-dose gamma radiation.

Some natural and synthetic antioxidants as stabilizers of beta-carotene conversion into vitamin A.

The effect of antioxidants (vitamins C and E, quercetin, probucol, butylated hydroxytoluene) on the oxidation of beta-carotene and its conversion into retinal under the influence of beta-carotene 15,15'- dioxygenase (CDO) from rat intestinal mucosa was studied. The activity of CDO decreased in the presence of oxidants. Antioxidants protected both the substrate and the enzyme. The extent of the protection depended on the antioxidant type. The combined injection of antioxidants and beta-carotene to animals completely or partially prevented the inhibition of the intestinal CDO which was caused by products of non-enzymatic oxidation of beta-carotene. Vitamins C and E, which protected the enzyme--substrate complex in vivo and in vitro, were found to be the most efficient protectors of beta-carotene conversion into retinal.

[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.

[Changes in the content and structure of the coenzyme A moiety in the liver of diabetic mice (db/db) administered a regimen of nicotinamide]. / Izmenenie soderzhaniia i struktury fonda koénzima A v pecheni diabeticheskikh myshei (db/db) pri kursovom vvedenii nikotinamida.

Alterations in the content and structure of CoA moiety typical of hyperlipogenesis (a rise in total and free CoA levels, a drop in short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios) were found in the liver of obese mice with non-insulin-dependent diabetes (db/db). The treatment of diabetic mice with nicotinamide, an antilipemic drug, was accompanied by a decrease in total and free CoA levels and a rise in short-chained fatty acyl-CoA content and short-chained fatty acyl-CoA/CoA and long-chained fatty acyl-CoA/CoA ratios, probably leading to the inhibition of the enzymes of primary lipogenesis steps. It is suggested that CoA moiety structure is essential as an integral index regulating the rate of fatty acid biosynthesis in diabetes mellitus.

[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.