The distribution of fluoride and calcium in the liver of the carbon tetrachloride-poisoned rat

Abstract

The effect of fluoride on CCl 4-induced hepatic calcium accumulation and the subcellular distribution of fluoride and calcium in CCl 4 poisoning were studied in 51-day-old rats. Treating rats with 2.5 m m NaF drinking water significantly elevated serum and whole liver fluoride levels above the levels observed in rats treated with 2.5 m m NaCl drinking water without altering serum or whole liver inorganic phosphate or calcium levels. An ip injection of 1.25 ml CCl 4/kg body wt elevated whole liver fluoride and calcium levels in the fluoride-treated group two- to threefold at 24 and 48 hr postinjection without altering serum fluoride, inorganic phosphate, or calcium levels or whole liver inorganic phosphate levels. The presence or absence of fluoride had no effect on the serum or whole liver inorganic phosphate or calcium levels observed at any time point. Between 87 and 90% of the excess fluoride was localized in the residual supernatant fluid while all of the excess calcium was localized in the purified mitochondrial pellet. This suggests that the hepatic calcium accumulation is not primarily in the form of hydroxyapatite. The elevation of the whole liver fluoride level above the serum level in the absence of hydroxyapatite suggests binding of fluoride to unknown compounds present in the damaged tissue. A CCl 4-induced increase in intracellular pH might explain an increase in the residual supernatant fluoride level to equal the serum level, but it seems unlikely that the intracellular pH would rise enough to explain the observed residual supernatant fluoride level. The possibility that CCl 4 damages an active cellular extrusion system for fluoride also needs to be considered as an alternative or contributing mechanism.