Effects of Lead on 4-Aminobiphenyl Pharmacokinetics in Liver, Kidney, Spleen, Testes, Heart, Lung and Hemoglobin Adduct for Rat Model


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Abstract

Lead affects almost every system in the body and 4-aminobiphenyl increases the incidence of bladder cancer among human exposed to aromatic amines, but little attention has been paid to the effects of lead (heavy metals) on the distribution and metabolic kinetics of 4-ABP (organic pollutants) in the organisms of the terrestrial ecosystems. In this study, male S.D. rats as model animals drinking tap water with and without lead with i.p. injection of 4-aminophenyl were used to study 4-aminobiphenyl pharmacokinetics with statistical analysis in three types of information systems: (1) hemoglobin adduct in the blood; (2) distribution concentrations in liver, kidney, spleen, testes, heart and lung; (3) relative weights of the six organs. Kinetic equations of 4-aminobiphenyl–hemoglobin adduct for two groups of rats drinking water with and without lead were all linear. Principal components were obtained based on three types of variants: (1) variants of distribution concentrations; (2) variants of relative weights; (3) variants of hemoglobin adduct, distribution concentrations and relative weights. Through a comparison of two groups of principal components, the result implied that lead changed 4-aminobiphenyl distribution kinetics in the six organs, had significant effects on the six organ relative weights, and had also significant effects on all thirteen variants as a whole. Correlation analysis of the principal components showed that lead could not significantly change the relation of hemoglobin adduct with time after dosing 4-aminobiphenyl. However, another result indicated that lead considerably improved the correlation between hemoglobin adduct and the thirteen variants as a whole. This implied that hemoglobin adduct could characterize all the thirteen variants as an index of 4-aminobiphenyl pharmacokinetics for the rats drinking water with lead, which conclusion was not suitable for the rats drinking water without lead. The research indicated that heavy metals existing in the organisms play an important role in the studies on pharmacotoxicology of organic pollutants. Frequently, various xenobiotics (heavy metals and organic pollutants) enter organisms simultaneously, therefore heavy metals should be considered comprehensively in the pharmacotoxicology of organic pollutants in animals in the terrestrial ecosystems theoretically and practically.

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