1-3-dimethylthiourea and citiolone

The Arrhenius plot of inactivation (killing) rates of V-79 Chinese hamster cells exposed to hypothermia contains a break at about 8 degrees C, which corresponds to the minimum inactivation rate, implying that there are distinct hypothermic damage mechanisms above (Range I = 8 to +25 degrees C) and below (Range II = 0 to +8 degrees C) 8 degrees C. Several membrane-permeable hydroxyl free radical scavengers, N-acetylhomocysteinethiolactone (citiolone), dimethylthiourea (DMTU), and dimethyl sulfoxide (DMSO), were tested for their ability to protect cells exposed to hypothermic temperatures of 10 degrees C (Range I) or 5 degrees C (Range II) as a function of time in a system that is uncomplicated by previous hypoxia. Citiolone (3 mM) protected cells in Range I, but not in Range II. To date, citiolone is the only agent that protects in Range I. Adenosine was of no benefit in Range I. Glycine (5 mM) protected cells in Range II, but not in Range I. DMSO (10 mM) was ineffective in Range II, while DMTU (10 mM) protected cells in Range II, but not in Range I. The combination of DMTU and citiolone had a synergistic protective effect on the cells during 10 degrees C exposure (Range I). However, the combination of DMTU and citiolone is neither synergistic nor additive at 5 degrees C (Range II).

Topics: Adenosine; Animals; Cell Death; Cell Division; Cell Line; Cell Survival; Cold Temperature; Cricetinae; Cricetulus; Cryopreservation; Cryoprotective Agents; Glycine; Thermodynamics; Thiophenes; Thiourea; Time Factors

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.

Topics: 1-Methyl-3-isobutylxanthine; Alloxan; Animals; Biological Factors; Cell Survival; Cells, Cultured; Cytokines; Free Radicals; Interferon-gamma; Interleukin-1; Islets of Langerhans; Peroxides; Rats; Rats, Inbred Strains; Recombinant Proteins; Streptozocin; tert-Butylhydroperoxide; Thiophenes; Thiourea; Tumor Necrosis Factor-alpha