Premium
THE EFFECT OF PRECURSORS OF PYRIDINE NUCLEOTIDES ON POISONING BY CARBON TETRACHLORIDE
Author(s) -
Gallagher CH
Publication year - 1960
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1960.26
Subject(s) - carbon tetrachloride , chemistry , nicotinic agonist , nicotinic acids , glutathione , biochemistry , intraperitoneal injection , pharmacology , organic chemistry , medicine , receptor , enzyme
SUMMARY The intraperitoneal injection of either nicotinic acid or DL‐tryptophane, which are precursors of pyridine nucleotides, reduced considerably the death rate in rats subsequent to the administration by stomach tube of doses of carbon tetrachloride which were usually lethal. The greatest reduction in death rate was obtained when nicotinic acid or DL‐trypophane was given two days before CCl 4 . Large doses of nicotinic acid injected five hours after CCl 4 was administered did not prevent deaths. Nicotinic acid, which is a direct precursor of pyridine nucleotides, was more effective under the experimental conditions of this study in preventing deaths from CCl 4 poisoning than DL‐tryptophane, which is a precursor of nicotinic acid. Choline chloride, L‐methionine, reduced glutathione, glucose and ethylenediaminetetra‐acetic acid did not appreciably reduce the death rate due to subsequent CCl 4 administration within the limits of this study. In rats killed 20 hours after the administration of a lethal dose of CCl 4 , there was a fall of more than 50 p.c. in the extinction coefficient at 260 mμ (E 260 ) of acid extracts of fresh liver homogenates or mitochondria prepared in 0.25 M sucrose compared with the figures for normal rats. The loss of material absorbing at 260 mμ in the homogenates was from the mitochondrial component. Prophylactic injections of nicotinic acid maintained almost normal E 260 values in acid extracts of liver homogenates of rats given CCl 4 . Injection of nicotinic acid without a subsequent dose of CCl 4 did not result in an increase of E 260 values above normal. It is probable, therefore, that nicotinic acid stimulates a rapid replacement of pyridine nucleotide lost from mitochondria as a result of CCl 4 administration. Greatest protection against the loss of E 260 values was obtained when nicotinic acid was given two to three days before CCl 4 . The relationship between mitochondrial E 260 values and the lethal effects of CCl 4 is discussed.