To clarify the mechanism of cytotoxicity induced by captopril (Cp), in
teractions between tissue protein and Cp were studied by the enzyme-li
nked immunosorbent assay (ELISA) method. The amide-linked adducts [hem
ocyanin from keyhole limpet-Cp adduct (KLH-Cp) and poly-L-Lys-Cp adduc
t (pLys-Cp)] using carbodiimide, and a disulfide-linked adduct [ovalbu
min-Cp adduct (OVA-Cp)] were prepared. To determine the formation of t
he protein-Cp adduct, rabbit antisera against KLH-Cp was employed. The
immunoreactivities with pLys-Cp and OVA-Cp against anti KLH-Cp sera w
ere elevated when compared with the unmodified protein. With the inhib
ition ELISA, this antisera was useful for detecting the Cp disulfide-l
inked conjugate. In kidney cytosol, a high level of immunoreactivity w
as observed. Plasma and liver cytosol reactivities were similar, and s
imilar to 40% against kidney cytosol. Thus, a method for the detection
of the Cp-protein adduct using ELISA has been established. Formation
of the Cp-protein adduct was observed in rat plasma and in liver and k
idney cytosol. These findings suggest the possibility that the formati
on of Cp-protein adduct is partially related to cytotoxicity in liver.