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Biomedical subjects

F Coulston

Publications and source records attributed to F Coulston.

At least 19 recordsLinked to original sources

Effects of short-term inhalation exposure to 1-nitropropane and 2-nitropropane on rat liver enzymes.

Male Sprague-Dawley rats were exposed to vapors of 1-nitropropane (1-NP) and 2-nitropropane (2-NP) at air concentrations of 100 ppm for 7 hours per day on four consecutive days. Livers were analyzed for enzymatic activities after 1-, 2-, and 4-day inhalation periods. Liver microsomal cytochrome P450 was depressed by 2-NP and elevated following exposure to 1-NP. Levels of cytochrome b5 were slightly increased in rats exposed to 1-NP and remained unchanged after inhalation of 2-NP. Total glutathione (GSH), GSH S-transferase, and UDP-glucuronosyltransferase activities were enhanced by 2-NP. 1-NP induced GSH peroxidase while 2-NP did not. Glutathione reductase was not altered after exposure to either isomer. No changes in the microsomal malondialdehyde content as a measure of lipid peroxidation and in the levels of serum aspartate transferase and serum glutamic oxaloacetic transaminase were observed during a 4-day exposure period in either of the exposed groups compared to control animals.

Animals

Bile acid conjugation in the chimpanzee: effective sulfation of lithocholic acid.

To characterize the hepatic biotransformation in the chimpanzee of the primary bile acid chenodeoxycholic acid (chenic) and its major bacterial metabolite lithocholic acid (lithocholic) a mixture of trace amounts of 14C-lithocholic and 3H-chenic was injected intravenously into two animals with a bile fistula; the chemical form of radioactivity appearing in bile was inferred using thin layer chromatography. About 80% of chenic, and 70% of lithocholic was recovered in 90 min. Chenic was completely conjugated in bile, appearing predominantly as chenyltaurine (52%) and chenylglycine (37%). An unidentified conjugate (about 11%) was also found. Lithocholic was excreted completely as taurine and glycine conjugates, but the majority (63%) of conjugates was sulfated. Sulfation increased progressively with time, and lithocholylglycine was sulfated more than lithocholyltaurine. We conclude that the chimpanzee is similar to man in that the secondary bile acid lithocholic is efficiently sulfated. The chimpanzee thus differs from the baboon and rhesus monkey which sulfate lithocholic poorly. However, the chimpanzee differs from man and is similar to the baboon and rhesus monkey in showing preferential conjugation of bile acids with taurine. The results imply that hepatotoxicity caused by chenic, which is well documented in the rhesus monkey and baboon and has been related to defective lithocholic sulfation, should not occur in the chimpanzee.

Animals

Endocrine effects of chlorinated hydrocarbons in rhesus monkeys.

After the rhesus monkey was demonstrated to be a suitable model for man in both metabolic and endocrinological studies, effects of hexachlorobenzene (HCB) and polychlorinated biphenyls (PCB) on the pattern of sexual hormones in cycling female rhesus monkeys were investigated. After confirmed ovulation, four adult female rhesus monkeys were treated during the following cycle with 4 mg/kg/day of HCB, and four other monkeys were treated with the same dose of Clophen A 30. Ovulation was blocked in three PCB-treated and one HCB-treated monkeys. Whereas the levels of luteinizing hormone and follicle-stimulating hormone did not seem to be changed directly by the treatment, low estrogen levels were found during the anovulatory cycles. Studies with PCB- and HCB-treated superovulated rats indicated interaction of the chemicals with ovarian steroidogenesis. Altered hepatic steroid metabolism may also cause low estrogen levels in treated animals.

Animals

Environmental chemical-induced immune dysfunction.

Antibody formation, endotoxin sensitivity, and resistance to a challenge malarial infection were evaluated in mice fed a diet containing polychlorinated biphenyl (PCB) (Aroclor 1242) or hexachlorobenzene (HCB). Antibody synthesis to the antigen sheep RBC (SRBC) was significantly depressed in the PCB- and HCB-treated (167 ppm) animals as evidenced by the fact that control mice elicited an approximate twofold increase in antibody formation over the chemical-treated mice. Serum IgA concentrations in the PCB- and HCB-treated mice were consistently 40--80 mg/dl lower than control values. Gram-negative endotoxin (Salmonella typhosa) sensitivity in PCB- and HCB-treated mice was increased 5.2- and 32-fold, respectively, following the dietary administration of 167 ppm of Aroclor 1242 or HCB for 6 weeks. An endotoxin hypersusceptibility was also noted at 3 weeks after dietary administration. Decreased resistance to a malaria challenge was also demonstrated in the xenobiotic-treated mice. A 20% decrease in mean survival time of mice fed Aroclor 1242 for 3 to 6 weeks and inoculated with Plasmodium berghei (NYU-2) was observed. Infected mice which had received HCB for 3 or 6 weeks manifested reductions in mean survival time of 24 and 31%, respectively. The data indicated that environmental chemical contaminants impair host resistance and, since no concomitant histopathological alterations were observed in the treated mice, the evaluation of immune parameters may possibly be a sensitive indicator of toxicity.

Animals