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Effect of chlordecone on carbon tetrachloride-induced increase in calcium uptake in isolated perfused rat liver

Journal Article · · Toxicol. Appl. Pharmacol.; (United States)
Intracellular accumulation of Ca/sup 2 +/ can occur in the livers of animals poisoned with a toxic dose of CCl/sub 4/. We have reported even greater accumulation of cytosolic Ca/sup 2 +/ in animals treated with an ordinarily nontoxic dose of CCl/sub 4/ in combination with prior exposure to chlordecone (CD). Present studies were designed to examine if intact perfused livers obtained from animals receiving either CCl/sub 4/ (100 microliter/kg, ip) alone or in combination with prior dietary exposure to 10 ppm CD for 15 days accumulated /sup 45/Ca from the perfusate. Livers obtained at 0, 1, 4, 6, 12, 24, and 36 hr after a single CCl/sub 4/ injection were perfused with Krebs-Ringer bicarbonate buffer containing erythrocytes, bovine serum albumin, and dextrose. After a 15-min equilibration, /sup 45/Ca was added to the perfusate, and the perfusion was continued for 30 min. Hepatic /sup 45/Ca accumulation in CCl/sub 4/-treated animals in the whole liver or in the subcellular organelles obtained from perfused liver was not significantly different from corn oil controls. In the CD + CCl/sub 4/ combination treatment, /sup 45/Ca accumulation followed a biphasic pattern with the first increase at 1 hr and then a progressive rise starting at 12 hr after CCl/sub 4/ administration. Mitochondrial, microsomal, and cytosolic fractions from perfused liver showed a progressive rise in /sup 45/Ca at late time periods, which is indicative of unregulated and irreversible influx of extracellular Ca/sup 2 +/ into these livers. These studies demonstrate that cytosolic Ca/sup 2 +/ progressively increases as a result of the unregulated entry of extracellular Ca/sup 2 +/.
Research Organization:
Univ. of Mississippi Medical Center, Jackson
OSTI ID:
5527725
Journal Information:
Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 2; ISSN TXAPA
Country of Publication:
United States
Language:
English

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