Production and toxicological application of anti-paraquat antibodies

For the purpose of the establishment of immunoassay for paraquat, polyclonal and three monoclonal antibodies (MoAbs), named APM-1, APM-2 and APM-3, have been produced. In order to evaluate the ability of polyclonal antibody and three MoAbs to recognize various kinds of bipyridyl herbicides and similar congeners of paraquat, a RIA (radioimmunoassay) and a competition enzyme-linked immunosorbent assay (ELISA) using avidin-biotin complex (ABC) were developed, respectively. Both the polyclonal antibody and the three MoAbs strongly recognized paraquat and slightly did other analogs. By use of both antiserum and MoAbs, less than 0.5 ng of paraquat dichloride was detectable by RIA and less than 1 ng of herbicide was detectable by ELISA. A good correlation between the ELISA and the corresponding RIA was obtained (r = 0.92). The determination of paraquat in tissues of paraquat-poisoned cadavers was also carried out by RIA and ELISA. For the attempt on immunotherapy for paraquat, anti-paraquat antibody conjugated to Hollow Fiber Kidney (HFK) was prepared, and within one min after starting dialysis of 50 ml of normal human serum containing 0.1 mg of paraquat dichloride, 25% of the amount of paraquat administered was removed. On the other hand, intravenous administration of anti-paraquat antibodies to rats have been studied. After intravenous paraquat injection of 0.1 mg/kg, the plasma paraquat concentration from rats pretreated with anti-paraquat antibodies was significantly increased but the amount of paraquat excreted in urine was significantly decreased compared to the control group. The concentration of paraquat in bile and organs except liver, was not changed by the treatment, but the paraquat level in liver was significantly increased. Although this immunotherapy for an acute paraquat poisoning succeeded to sequester paraquat in plasma compartment, it could not prevent paraquat from accumulating in tissues.