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Liver and pancreas concentrations of calcium and zinc after chronical nickel ingestion by the rat
Toxicology 81
A40 II-13
SUSCEPTIBILITY TO CARBON TETRACHLORIDE INDUCED LIVER TOXICITY IN DEVELOPING RATS Andreas Kistler, Andreas Steiger, Ernst BGhler and Peter Keller Biological Pharmaceutical and Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., 4002 Basle, Switzerland The hepatotoxic effect of carbon tetrachloride (CC14) appears to depend on prior hepatic activation. The capacity of drug metabolism in rats is low in newborns and remains low until the third or fourth postnatal week. Hence, if the hepatotoxicity of CC14 would only depend on prior activation by hepatic biotransformation, young rats should be less sensitive than adult ones.However, assessed by LD50 , CC14 was about 5 times more toxic in newborns and about twice as toxic in 4-, 12- and 20-day-old rats than in adults. Furthermore, hepatotoxicity of CC14, as determined by activity changes of plasma and liver enzymes, liver triglyceride content and degree of fatty infiltration into the liver, was found to be similar in 4- and 12-day-old rats as in adult ones. These findings suggest a different mechanism of CC14 toxicity in young and in adult rats.
II-14
LIVER AND PANCREAS CONCENTRATIONS OF CALCIUM AND ZINC AFTER C H R O NICAL N I C K E L INGESTION BY THE RAT Maria Isabel Sanchez Reus, Salvador Bondia, B a r t o l o m ~ Ribas and Angel Santos Ruiz. Department of Biochemistry, Faculty of Pharmacy, Madrid, Spain. The biological interest for nickel toxicity in the occupational exposure and for its essentiality in metabolism, is being w e l l documented, as it is evidenced by the recents international meetings. Experiments were carried out w i t h male and female Wistar rat groups, feeded during 4 rat generations with I00 and 200 ~ g Ni/ ml drink water. Calcium, zinc and n i c k e l determinations in several organs are realized by atomic absorption spectrophotometry. Insulin and a - a m y l a s e levels "in vivo" and the secretion of insulin in isolated and perfused rat pancreas were also made. Interactions between Ca, Zn and Ni in the rat liver and pancreas are detected, The l o n g n i c k e l ingestion allows the accumulation of this cation in several organs: e.g. from 0.05 0.001 to 3.38 2.O7 ppm in the pancreas; the liver does not show any slgnificatlve difference for none of the three studied cations. N i c k e l ingestion increases Ca, Zn and N i levels in the pancreas: Ca f r o m 2.720 to 4.020 ~ / m g protein, and Zn from 0.840 to 1.314 ~ g / ~ e protein levels. orai ingestion of n i c k e l induces calcium and zinc a c c u m u l a tion by the pancreas, in accordance to an active insulin secretion after the stimulus of glucose in an isolated and perfused rat pancreas.
A40 II-13
SUSCEPTIBILITY TO CARBON TETRACHLORIDE INDUCED LIVER TOXICITY IN DEVELOPING RATS Andreas Kistler, Andreas Steiger, Ernst BGhler and Peter Keller Biological Pharmaceutical and Pharmaceutical Research Department, F. Hoffmann-La Roche & Co. Ltd., 4002 Basle, Switzerland The hepatotoxic effect of carbon tetrachloride (CC14) appears to depend on prior hepatic activation. The capacity of drug metabolism in rats is low in newborns and remains low until the third or fourth postnatal week. Hence, if the hepatotoxicity of CC14 would only depend on prior activation by hepatic biotransformation, young rats should be less sensitive than adult ones.However, assessed by LD50 , CC14 was about 5 times more toxic in newborns and about twice as toxic in 4-, 12- and 20-day-old rats than in adults. Furthermore, hepatotoxicity of CC14, as determined by activity changes of plasma and liver enzymes, liver triglyceride content and degree of fatty infiltration into the liver, was found to be similar in 4- and 12-day-old rats as in adult ones. These findings suggest a different mechanism of CC14 toxicity in young and in adult rats.
II-14
LIVER AND PANCREAS CONCENTRATIONS OF CALCIUM AND ZINC AFTER C H R O NICAL N I C K E L INGESTION BY THE RAT Maria Isabel Sanchez Reus, Salvador Bondia, B a r t o l o m ~ Ribas and Angel Santos Ruiz. Department of Biochemistry, Faculty of Pharmacy, Madrid, Spain. The biological interest for nickel toxicity in the occupational exposure and for its essentiality in metabolism, is being w e l l documented, as it is evidenced by the recents international meetings. Experiments were carried out w i t h male and female Wistar rat groups, feeded during 4 rat generations with I00 and 200 ~ g Ni/ ml drink water. Calcium, zinc and n i c k e l determinations in several organs are realized by atomic absorption spectrophotometry. Insulin and a - a m y l a s e levels "in vivo" and the secretion of insulin in isolated and perfused rat pancreas were also made. Interactions between Ca, Zn and Ni in the rat liver and pancreas are detected, The l o n g n i c k e l ingestion allows the accumulation of this cation in several organs: e.g. from 0.05 0.001 to 3.38 2.O7 ppm in the pancreas; the liver does not show any slgnificatlve difference for none of the three studied cations. N i c k e l ingestion increases Ca, Zn and N i levels in the pancreas: Ca f r o m 2.720 to 4.020 ~ / m g protein, and Zn from 0.840 to 1.314 ~ g / ~ e protein levels. orai ingestion of n i c k e l induces calcium and zinc a c c u m u l a tion by the pancreas, in accordance to an active insulin secretion after the stimulus of glucose in an isolated and perfused rat pancreas.