Antioxidative properties of organotellurium compounds in cell systems.
The protective/antioxidative properties of diaryl tellurides were demonstrated in cellular systems of increasing complexity. In the presence of glutathione, bis(4-hydroxyphenyl) telluride (1a), bis(4-aminophenyl) telluride (1d) and bis(2-carboxyphenyl) telluride (1h) reduced by more than 50% t-butyl hydroperoxide-induced cell death in lung fibroblast cultures at concentrations below 2 microM. Bis(2,6-dimethyl-4-hydroxyphenyl) telluride (2b) reduced by more than 50% leukocyte-mediated and phorbol-12-myristate-13-acetate-stimulated damage to Caco-2 cells at 0.1 microM concentration. As judged by their abilities to reduce formation of thiobarbituric acid reactive substances at concentrations close to 1 microM, diaryl tellurides 1a, 1d and 2b protected rat kidney tissue against oxidative damage caused by anoxia and reoxygenation. The organotellurium compounds also offered protection after systemic administration. In the presence of diaryl telluride 2b (0.1-1 microM), the ischemia/reperfusion-induced vascular permeability increase in the hamster cheek pouch was significantly reduced as compared with the control. Some of the most active organotellurium cell protectants were evaluated for their ability to inhibit formation of the inflammatory mediators leukotriene B4 and interleukin-1beta. An inhibitory effect on the secretion of these species was seen for compounds 1a and 2b at or above 10 microM concentrations. The protective effects of diaryl tellurides against t-butyl hydroperoxide-induced cell injury can be ascribed mainly to the peroxide-decomposing, glutathione peroxidase-like capacity of the compounds. The chain-breaking, electron- or hydrogen atom-donating ability of diaryl tellurides seems to be the main reason for their protection against leukocyte-mediated cell damage in Caco-2 cells and in the oxidatively challenged rat kidney and hamster cheek pouch.
Wieslander
E
E
Preclinical R & D, Astra Draco AB, Lund, Sweden.
Engman
L
L
Svensjö
E
E
Erlansson
M
M
Johansson
U
U
Linden
M
M
Andersson
C M
CM
Brattsand
R
R
D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D018836:Inflammation Mediators; D007511:Ischemia / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D009942:Organometallic Compounds / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020122:tert-Butylhydroperoxide
D000814:Aniline Compounds; D000975:Antioxidants; D001565:Benzoates; D018836:Inflammation Mediators; D009942:Organometallic Compounds; D010545:Peroxides; D010636:Phenols; C111214:bis(2-carboxyphenyl)telluride; C111213:bis(4-aminophenyl)telluride; C111215:bis(4-hydroxyphenyl)telluride; D020122:tert-Butylhydroperoxide