Detoxifying potential of thioproline against N-nitroso compounds, N-nitrosodimethylamine and N-nitrosocimetidine.

Thioproline (TPRO), an effective nitrite trapping agent in vivo, was examined for its detoxifying ability in rats against N-nitrosodimethylamine (NDMA) and N-nitrosocimetidine (NCIM). When NDMA (37-101.5 mg/kg) was administered with TPRO (532 mg/kg), no influence of TPRO on NDMA-induced lethality and histological results in liver were observed. NDMA oxygenase activity measured by formaldehyde formation was not affected either. Denitrosation is a route of detoxication of N-nitroso compounds. When NCIM (100 mg/kg), a direct acting mutagen but not carcinogen, was given by gavage with TPRO, urinary excretion of N-nitrosothioproline (NTPRO) in rats apparently increased compared with TPRO alone. This result shows that TPRO is a trapping agent in vivo for nitrosating (NO) species originating from N-nitroso compounds, e.g., NCIM, which are denitrosated non-enzymatically in stomach acidic conditions. Transnitrosation from NDMA to TPRO, where enzymatic denitrosation is required, did not occur in measurable amount after oral administration of NDMA and TPRO.