Investigations on the presence of porphyrinogen carboxy-lyase inhibitor in the liver of rats intoxicated with hexachlorobenzene

1. 1. It has been reported that hexachlorobenzene (HCB) in vivo produces hepatic porphyrinogen carboxy-lyase (PCL) decrease and pentachlorophenol (PCP) is one of its metabolites. In order to investigate if such decrease is due to an enzyme inhibitor present in the porphyric livers, the effects of th...

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Autores principales: De Molina, M.D.C.R., De Calmanovici, R.W., De Viale, L.C.S.M.
Formato: JOUR
Materias:
rat
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_0020711X_v12_n5-6_p1027_DeMolina
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Sumario:1. 1. It has been reported that hexachlorobenzene (HCB) in vivo produces hepatic porphyrinogen carboxy-lyase (PCL) decrease and pentachlorophenol (PCP) is one of its metabolites. In order to investigate if such decrease is due to an enzyme inhibitor present in the porphyric livers, the effects of the following additions on the normal rat liver PCL activity were investigated: (a) a porphyric liver preparation (free of porphyrins), (b) a heat deproteinized porphyric liver preparation, (c) HCB, PCP, several chloro and nitrophenols and other related compounds. 2. 2. The results of (a) and (b) would indicate that in porphyric liver there is probably an inhibitor tightly bound to the "porphyric" enzyme which is not separated by Sephadex G-25 and that produces an inhibition of "normal" enzyme smaller than that observed in vivo for HCB, the difference being perhaps due to a protein synthesis level action. 3. 3. From the results of (c) it is observed that (i) there are several drugs that inhibit hepatic PCL in different degrees, PCP, tetrachlorophenol and 2,4-dinitrophenol being the most effective, while HCB has no effect at any of the assayed concentrations, (ii) the inhibitory effect of these compounds could be mainly due to the presence of phenolic group and increased by the presence of electrophilic groups in the benzene ring, (iii) the above mentioned inhibitor made evident by the heating assays could be PCP, HCB being discarded because the absence of effect. However, the marked inhibitory effect of PCP decreases and disappears at lower concentrations. 4. 4. The physiological role of PCP in the production mechanism of HCB porphyria is discussed. © 1980.