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Some Acute Effects of Arsenic On The Liver.

Albores-Medina, Arnulfo. (1988) Some Acute Effects of Arsenic On The Liver. Doctoral thesis, University of Surrey (United Kingdom)..

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Abstract

The livers of rats dosed acutely with As III developed a lipid vacuolation of the periportal area, a general loss of glycogen, dilation of the bile canaliculi, and various degrees of mitochondrial condensation. These morphological changes were more evident in phenobarbitone pretreated rats.As III induced hepatic haem oxygenase activity, regardless of the pretreatment. This induction was reflected by an increase in the excretion of bilirubin 6 hr after treatment. The source of haem being degraded was investigated by injecting rats with 5- amino-[4- 14C]-laevulinic acid. The radioactive label was excreted before the bulk of the bilirubin, suggesting that hepatic haem was the first to be degraded. The excretion of haem is presumably due to haemoglobin breakdown, since immunoelectrophoresis show haptoglobin to be increased in the bile of As III rats. Cytochrome P-450 levels and ethoxycoumarin-O-deethylase activity gradually decreased with time after As III administration. The effect appears to be isoenzyme non-specific because As III administration to phenobarbitone pretreated rats significantly decreased pentoxyresorufin-O-deethylase, benzphetamine-N-demethylase, and ethoxyresorufin-O-deethylase activities, but did not significantly affect ethoxycoumarin-O-deethylase . In vitro, and at high concentrations, As III produced no change in the rat liver microsomal cytochrome P-450 content, but produced a fall in cytochrome concentration when NADPH was added. No effect was found at concentrations likely to be present in vivo. Hence, it appears that As III may bind apo-cytochrome P-450, rather than holo-cytochrome P-450, and as a consequence of this, the "free" haem pool increases, triggering the induction of HO .

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Albores-Medina, Arnulfo.
Date : 1988
Additional Information : Thesis (Ph.D.)--University of Surrey (United Kingdom), 1988.
Depositing User : EPrints Services
Date Deposited : 24 Apr 2020 15:27
Last Modified : 24 Apr 2020 15:27
URI: http://epubs.surrey.ac.uk/id/eprint/855052

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