Abstract
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.
MeSH Terms
1-Methyl-3-isobutylxanthine/pharmacology
Alloxan/pharmacology
Animals
Biological Factors/pharmacology
Cell Survival/drug effects
Cells, Cultured
Cytokines
Free Radicals
Interferon-gamma/pharmacology
Interleukin-1/pharmacology
Islets of Langerhans/cytology,drug effects
Peroxides/pharmacology
Rats
Rats, Inbred Strains
Recombinant Proteins/pharmacology
Streptozocin/pharmacology
Thiophenes/pharmacology
Thiourea/analogs & derivatives,pharmacology
Tumor Necrosis Factor-alpha/pharmacology
tert-Butylhydroperoxide
Chemicals
Biological Factors
Cytokines
Free Radicals
Interleukin-1
Peroxides
Recombinant Proteins
Thiophenes
Tumor Necrosis Factor-alpha
Streptozocin
Alloxan
citiolone
Interferon-gamma
1,3-dimethylthiourea
tert-Butylhydroperoxide
Thiourea
1-Methyl-3-isobutylxanthine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Sumoski W
Department of Medicine, University of Alberta, Edmonton, Canada.
Baquerizo H
Rabinovitch A
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