Biomedical subjects

S D Mercurio

Publications and source records attributed to S D Mercurio.

4 recordsLinked to original sources

PubMed1987

Mercaptans decrease selenium-dependent glutathione peroxidase activity in the chick.

A variety of mercaptans, especially the beta-mercaptocarboxylic acids, inhibited the selenium (Se)-dependent glutathione peroxidase (SeGSHpx) activity of chick liver postmitochondrial supernatant or cytosol and of purified bovine erythrocyte SeGSHpx. The effects of mercaptans and a glutathione analogue on Se utilization were determined by subcutaneous injection of test compounds into vitamin E-deficient chicks fed diets containing 0.1 ppm Se (as Na2SeO3) at times when greater than 50% of vitamin E- and Se-deficient chicks showed the vitamin E-, Se-deficiency disease exudative diathesis (ED). D-(-)-Penicillamine hydrochloride (the positive control model compound), sodium beta-mercaptopyruvate, t-butyl mercaptan and S-methylglutathione (nonmercaptan glutathione analogue) decreased SeGSHpx activity in chick liver postmitchondrial supernatants within 24 h of injection and increased the incidence of ED within 4 d. Other mercaptans tested did not increase ED incidence or affect liver, kidney or plasma SeGSHpx activities. Although mercaptosuccinic acid, N-(2-mercaptopropionyl)glycine and sodium thioglycolate each strongly inhibited SeGSHpx in vitro, each also significantly increased chick mortality in the dosage range tested; therefore, their effects on SeGSHpx in vivo could not be evaluated. It appears that the beta-mercaptocarboxylic acids, mercaptans with a high degree of steric hinderance in close proximity to the thiol group and a close structural analogue of glutathione are capable of altering selenium status in chicks.

Animals↗

PubMed1986

Synthetic seleno-organic compound with glutathione peroxidase-like activity in the chick.

The glutathione peroxidase activity catalyzed by the seleno-organic anti-inflammatory drug Ebselen (registered under the trademark of the Natterman Corp. Cologne, FRG) [PZ51, 2-phenyl-1,2-benzisoselenazol-3(2H)on], as measured by NADPH oxidation, was inhibited in vitro by the selenium-dependent glutathione peroxidase (SeGSHpx) inhibitors aurothioglucose and D-(-)penicillamine HCl. Vitamin E- and selenium-deficient chicks were given 0, 80 or 320 ppm PZ51 in diets devoid of vitamin E and supplemented with low levels of sodium selenite (0.04 ppm selenium added to the basal diet containing ca. 0.015 ppm selenium) when a small number of chicks (ca. 13%) had exudative diathesis (ED). By 24 hr, the high PZ51 dose (320 ppm) delayed the onset of ED compared to untreated controls. Similarly, vitamin E-deficient chicks fed diets containing 0, 80, 160, 320, 640 or 1280 ppm PZ51 and supplemented with 0.04 ppm selenium showed ED in inverse proportion to log PZ51 dose. Plasma and liver post-mitochondrial supernatant samples from these chicks also exhibited log-linear relationships between dietary PZ51 level and selenium content or SeGSHpx-like activity. The amount of SeGSHpx-like activity for chicks given PZ51 above that determined for untreated chicks was extractable into ethanol, indicating that those PZ51-associated increases were not due to protein-bound selenium or SeGSHpx. This suggests that selenium from PZ51 was not available to support synthesis of SeGSHpx. Dietary PZ51 (1280 ppm) or selenium (0.1 ppm) alone or in combination decreased the acute lethalities of nitrofurantoin or paraquat in vitamin E-adequate chicks. The results indicate that SeGSHpx-like activity in selenium-deficient chicks is increased by oral administration of PZ51, which appears to mimic the true enzyme by affording protection against clinical signs of selenium deficiency (i.e. ED) and pro-oxidant drug lethality.

Animals↗

PubMed1986

Selenium-dependent glutathione peroxidase inhibitors increase toxicity of prooxidant compounds in chicks.

The acute lethality of paraquat (1, 1'-dimethyl-4,4'-bipyridinium dichloride; also methyl viologen) for chicks was reduced in a dose-dependent manner by adding to a selenium-deficient torula-yeast-based diet low concentrations (0.02-0.04 ppm) of selenium (Se) as either Na2SeO3, selenomethionine or a high Se yeast without significantly increasing plasma Se-dependent glutathione peroxidase (Se GSH-Px) activity. Similarly, chicks orally dosed with 100 mg nitrofurantoin [N-(5-nitro-2 furfurylidine)-1-aminohydantoin] per kilogram had highest mortalities in the Se-deficient (unsupplemented) group; lowest mortalities occurred in chicks supplemented with 0.2 ppm Se; chicks supplemented with 0.02 ppm Se survived at rates not statistically different from chicks either unsupplemented or supplemented with 0.2 ppm Se. The activities of SeGSH-px in various vital organs were significantly elevated by supplementation of 0.2 ppm Se to Se-deficient chicks; but only kidney SeGSH-Px increased with 0.02 ppm Se. Additionally, no histopathology was observed in the vital organs of moribund chicks 5 or 24 h following nitrofurantoin administration at any dietary level of Se tested. Exposure of chicks to oxygen enhanced the toxicity of nitrofurantoin, but the protective effect of dietary Se was still evident. Two inhibitors of SeGSH-Px, D(-)-penicillamine X HCl and aurothioglucose, were found to increase the lethalities of both nitrofurantoin and paraquat. Aurothioglucose was most effective when administered simultaneously with the prooxidant compounds; penicillamine increased toxicities only when administered at least 24 h before paraquat or nitrofurantoin (it decreased nitrofurantoin lethality and did not significantly alter paraquat toxicity if given simultaneously). These data support an hypothesis that the protection offered by dietary Se against the acute toxicities of the prooxidant compounds paraquat and nitrofurantoin may be provided by SeGSH-Px in the chick.

Animals↗

PubMed1985

Drug-induced changes in selenium-dependent glutathione peroxidase activity in the chick.

The ability of aurothioglucose and D(-)-penicillamine hydrochloride to inhibit selenium-dependent glutathione peroxidase (SeGSH-Px) in vitro and to increase exudative diathesis in vitamin E-deficient chickens was studied. Aurothioglucose and penicillamine competitively inhibited SeGSH-Px in inverse proportion to the concentration of hydrogen peroxide and reduced glutathione, respectively, in chick liver postmitochondrial supernatant assay preparations. Neither drug inhibited glutathione reductase or superoxide dismutase at the concentrations tested; however, both inhibited catalase in a semilogarithmic fashion. This was true for both the purified bovine enzyme and chick liver homogenate. Aurothioglucose and penicillamine injected subcutaneously at the back of the neck increased exudative diathesis in vitamin E-deficient chickens fed 0.1 ppm Se, and effectively overcame the protective effect of selenium 72 h after injection in chicks fed vitamin E-free, low selenium diets supplemented with 0.0-0.1 ppm Se. Assays of plasma and of liver, lung and kidney postmitochondrial supernatants indicated that all observed reductions in SeGSH-Px activity preceded increases in exudative diathesis. Plasma and liver SeGSH-Px activities were lower at early times (6-24 h) after treatment with high doses of either drug. Lung SeGSH-Px activities were only lower in chicks receiving 240 mg penicillamine/kg 6 h after treatment; kidney SeGSH-Px activities were only lower in chicks treated with the highest dose of aurothioglucose 48 h after treatment. Brain SeGSH-Px activities were unaffected by drug treatment and the heart had higher SeGSH-Px activities only at 6 h after treatment with the highest dose of either drug compared to saline controls. Catalase activities in liver homogenates were only significantly altered by penicillamine; the highest dose caused the activity to be higher than that in saline-treated chicks. The cause of the lower SeGSH-Px activities could be either lower enzyme concentrations in tissues of the drug-treated groups and/or direct inhibition. Whatever the mechanism, it is concluded that exudative diathesis can be used to determine which drugs reduce SeGSH-Px activity in the chick.

Administration, Oral↗