Oxygen free radical scavengers protect rat islet cells from damage by cytokines.
A possible role for oxygen free radicals in mediating the cytotoxic effects of cytokines in islets was sought by the use of agents that scavenge free radicals. Rat islet cell monolayer cultures were incubated for 6 days with t-butylhydroperoxide, alloxan, streptozotocin, or the cytokines, interleukin 1, tumour necrosis factor, and interferon gamma, without and together with the oxygen free radical scavenger combination of dimethylthiourea and citiolone, and islet cell lysis was measured in a 51chromium cytotoxicity assay. The free radical scavengers significantly inhibited the islet cell cytotoxic effects of t-butylhydroperoxide and alloxan, but not streptozotocin. Similarly, the cytotoxic effects of the cytokine combinations of interleukin 1 plus tumour necrosis factor, interferon gamma plus tumour necrosis factor, and interferon gamma plus interleukin 1 were significantly inhibited by the free radical scavenger combination of dimethylthiourea and citiolone. These results suggest that the cytokine products of macrophages and lymphocytes infiltrating islets in Type 1 (insulin-dependent) diabetes may contribute to B-cell damage by inducing the production of oxygen free radicals in the islet cells.
Sumoski
W
W
Department of Medicine, University of Alberta, Edmonton, Canada.
Baquerizo
H
H
Rabinovitch
A
A
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000496:Alloxan / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines; D005609:Free Radicals; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D010545:Peroxides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013311:Streptozocin / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020122:tert-Butylhydroperoxide
D001685:Biological Factors; D016207:Cytokines; D005609:Free Radicals; D007375:Interleukin-1; D010545:Peroxides; D011994:Recombinant Proteins; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D013311:Streptozocin; D000496:Alloxan; C000486:citiolone; D007371:Interferon-gamma; C038983:1,3-dimethylthiourea; D020122:tert-Butylhydroperoxide; D013890:Thiourea; D015056:1-Methyl-3-isobutylxanthine