Protective effect of nicotinamide and 3-aminobenzamide on islet cell damage induced by gamma-interferon and tumor necrosis factor.
Mouse islet cell monolayers were damaged when cultured for five days in a medium containing 200 U/ml of recombinant murine interferon-gamma (IFN-gamma) and 300 U/ml of recombinant tumor necrosis factor (TNF). The cells formed granular clusters and ultimately floated in the medium; the floating cells proved to be dead by the trypan-blue dye-exclusion method. When 20 mM of nicotinamide or 5 mM of 3-aminobenzamide was supplemented to the medium, islet cell monolayers remained in the presence of the cytokines. 51Cr release studies showed that specific 51Cr release during five-day incubation with 200 U/ml of IFN-gamma and 300 U/ml of TNF was 30 +/- 4% (mean +/- SE). In a medium containing 20 mM of nicotinamide, together with IFN-gamma and TNF, specific 51Cr release was significantly reduced (12 +/- 3%, p less than 0.01). 3-aminobenzamide was effective at the level of 5 mM; specific 51Cr release was 2 +/- 5% (p less than 0.01). These results suggest that the mechanism by which IFN-gamma and TNF damage islet cells may be similar to that of streptozotocin and/or alloxan.
Yamada
K
K
Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan.
Ryu
E
E
Nonaka
K
K
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004357:Drug Synergism; D005260:Female; D007371:Interferon-gamma / Q000633:toxicity*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009536:Niacinamide / Q000494:pharmacology*; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D001549:Benzamides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009536:Niacinamide; D007371:Interferon-gamma; C025160:3-aminobenzamide