Prevention of CCl4-induced liver necrosis by the calcium chelator arsenazo III.
Arsenazo III (AIII) (100 mg/kg ip in saline) administration to Sprague-Dawley male rats 30 min before or 6 or 10 hr after CCl4 [1 ml/kg ip as a 20% (v/v) solution in olive oil] significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as demonstrated either by histology or by determination of isocitric acid dehydrogenase in plasma. AIII did not modify the CCl4 concentrations reaching the liver, the intensity of the covalent binding of CCl4-reactive metabolites to hepatic microsomal lipids, or the CCl4-promoted lipid peroxidation process at either 1 or 3 hr of poisoning. AIII administration enhanced glutathione (GSH) levels in liver and significantly prevented the CCl4-induced minor decreases in GSH content and the CCl4-induced increases in calcium content at 24 hr of intoxication. AIII treatment further enhanced the CCl4-induced decreases in body temperature of the poisoned rats. Results suggest that AIII's preventive effects might be related to its very well-known calcium-chelating properties, but that additional factors related to AIII's ability to increase GSH content in liver or to decrease body temperature of CCl4-intoxicated animals may also play a role.
de Ferreyra
E C
EC
Centro de Investigaciones Toxicológicas (CEITOX) CITEFA/CONICET, Provincia de Buenos Aires, Argentina.
Bernacchi
A S
AS
Villarruel
M C
MC
de Fenos
O M
OM
Castro
J A
JA
D000818:Animals; D001150:Arsenazo III / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002251:Carbon Tetrachloride / Q000378:metabolism / Q000633:toxicity*; D002252:Carbon Tetrachloride Poisoning / Q000097:blood / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
D001150:Arsenazo III; D002251:Carbon Tetrachloride; D007521:Isocitrate Dehydrogenase; D005978:Glutathione; D002118:Calcium