Implicações toxicologicas e bioquimicas de xenobioticos em Curimbata (Prochilodus scrofa, Steindachnner, 1881) um peixe tropical brasileiro

AUTOR(ES)
DATA DE PUBLICAÇÃO

2002

RESUMO

Cytochromes P450 constitute a superfamily of hemeproteins that play a vital role in the metabolism of a wide variety of compounds such as steroids, fatty acids, drugs and environmental pollutants. Xenobiotic metabolism and role of cytochrome P450 are important areas of molecular pharmacology and toxicology, and of great interest mainly in the studies on prevention of the damage caused by chemical pollutants. In this work we investigated the interaction of Trifluoperazine, Triton X-100 and Tween 80 with cytochrome P450, phase I and 11 enzymes and antioxidants defenses in Curimbatá, a brazilian teleost fish. Spectral characterization indicated a possible presence of a hemeprotein, with similar characteristics of cytochrome P450, in liver of Curimbatá; a peak at 418-420nm ("P420") decreased in the presence of xenobiotics. Purification of cytochrome P450 had been succeded by HPLC on hydrophobic column (Il-Boundapak - C18). Only one isoform of P450 - CYP1A - could be detected in Curimbatá hepatic microsomes. EROD and NADPH cytochrome P450 redutase were strongly inhibited by Triton X-100 and Tween 80 in a time- and concentration-dependent way. Triton X-100 and Tween 80 inactivated the system by interacting with the membrane. In the case of Triton X-100, that cause the alkylation in the hememoiety, P450 inactivation occurred even in monomers. However these enzymes were activated by Trifluoperazine (TFP) suggesting that only TFP was being metabolized by P450 system and that its metabolites could interact with P450 and inativeted it. Glutathione-S-Transferase, a phase 11 enzyme, was activated by the xenobiotics, suggesting that Curimbatá could metabolize these compounds. Analyses of antioxidant enzymes activities, lipoperoxidation levels and P450 contents showed a non-significative correlation between antioxidant effects and P450 system. Our results suggested that P450 is a potential biomarker of xenobiotic exposure, but its use need to be associated with other enzymes because xenobiotics can distinctly interact with each component of the system leading to the activation of some enzymes and inhibition of others

ASSUNTO(S)

peixe biotransformação (metabolismo) marcadores biologicos xenobiotica - toxicologia

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