Effects of Ethyl Carbamate and its Metabolites on the Antibody Response in Splenocyte Cults from Female Balb/C Mice

Abstract

To investigate a possible role by cytochrome P450 (P450) in ethyl carbamate-induced immunosuppression, an attempt to assess the ability of ethyl carbamate, its metabolites produced by P450 (i.e., ethyl N-hydroxycarbamate and vinyl carbamate), and methyl carbamate to suppress the polyclonal antibody response induced by bacterial lipopolysaccharide was made in splenocyte cultures isolated from female Balb/C mice. The results showed that vinyl carbamate and ethyl N-hydroxycarbamate were more immunosuppressive compared to ethyl carbamate. A structurally related analogue, methyl carbamate, did not suppress the antibody response. These results indicate that metabolism of ethyl carbamate by P450 may produce more immunosuppressive metabolites as in ethyl carbamate-induced carcinogenicity. A pre-incubation study with phenobarbital-induced liver microsomes in the presence of NADPH-generating system showed that the antibody response was suppressed by ethyl carbamate when splenocytes were pre-incubated with ethyl carbamate and microsomes simultaneously. Moreover, the suppression was completely recovered by the addition of a P450 inhibitor, aminoacetonitrile, in the pre-incubation. Taken together, the present results indicate that metabolism of ethyl carbamate by P450 enzyme(s) may be an important pathway to cause immunosuppression.

In vivo evaluation of ziram induced acute toxicity on pathomorphology of broiler chicken

“…In some cases central arteries showed fibromuscular dysplasia characterized by massive proliferation of endothelial cells. These changes in the spleen are in accordance with those reported by Foster et al (1979) and Jeong et al (1998) in ethyl carbamate toxicity of mice. Bursa: Histopathologically, bursa revealed mild degenerative changes in lymphoid cells along with the congestion.…”