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M C Henderson

Publications and source records attributed to M C Henderson.

63 records · Page 4Linked to original sources

Protective action of zinc against pyrrolizidine alkaloid-induced hepatotoxicity in rats.

The influence of Zn on the acute hepatotoxicity of pyrrolizidine alkaloids (PAs) was determined in male rats. Zinc, 72 mumol/kg as ZnCl2, was administered ip for 3 consecutive days, followed 16 h after the last dose by a single ip injection of purified mixed PAs (80, 120, or 160 mg/kg) obtained from tansy ragwort (Senecio jacobaea). Hepatotoxicity of the PAs was assessed by measuring the activities of plasma glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) and by histological examination of the liver. There was a dose-dependent increase in plasma GOT and GTP 24 h after PA administration, whereas no significant increase of these enzymes was seen after administering Zn alone. The 7-fold increase in plasma GOT and 12-fold increase in GPT after PA (120 mg/kg) were reduced to 2.4- and 2.1-fold, respectively, by Zn pretreatment. The PA-induced liver necrosis was either reduced in severity or abolished by Zn when the PA dose was 80 or 120 mg/kg. These results suggest a protective effect of Zn against PA hepatotoxicity. The protective effect was associated with a marked increase in liver metallothionein and a significant decrease in hepatic cytochrome P-450 content, aminopyrine N-demethylase activity, and in vitro microsomal conversion of the PAs to pyrroles. Liver nonprotein sulfhydryls were unchanged. The possible role of metallothionein in the sequestration of pyrrole metabolites merits further investigation.

Alanine Transaminase↗

Covalent binding of carbaryl (1-naphthyl-N-methyl-carbamate) to rat liver microsomes in vitro.

Enzyme mediated binding of carbaryl (1-naphthyl-N-methylcarbamate) to rat hepatic microsomes occurred in vitro in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and oxygen and was inhibited by nitrogen, carbon monoxide, reduced glutathione, cysteine, N-ethyl maleimide, and 2-diethylaminoethyl-2,2'-diphenylvalerate-HCl (SKF 525-A). Binding was markedly increased, 2- to 3-fold, by pretreatment of animals with phenobarbital or 3-methylcholanthrene and appeared to be dependent on the production of an active metabolite which was formed oxidatively in liver microsomes by cytochrome P-450 mixed-function oxidases. SDS-polyacrylamide disc gel electrophoresis of ether-extracted, solublized microsomes and the distribution of radioactivity after Pronase digestion, treatment with 1-fluoro-2,4-dinitrobenzene, and extraction with ethyl acetate and ether at pH 9 and 1 indicated that the radiolabeled products were covalently bound to amino acid residues of microsomal protein.

Animals↗

Comparative effects of antioxidants on the toxicity of mixed pyrrolizidine alkaloids from Senecio jacobaea in mice.

The comparative effects of the antioxidants, butylated hydroxyanisole (BHA), ethoxyquin, and cysteine on pyrrolizidine-alkaloid-induced (PA-induced) lethality and acute hepatotoxicity were assessed in female mice. Diets containing 0.75% BHA, 0.25% ethoxyquin, or 1% cysteine were fed to mice for 10 d before the ip administration of mixed PAs from Senecio jacobaea (tansy ragwort), 280 mg/kg. Without the dietary antioxidants, the PAs produced 100% mortality in 24 h. The BHA and ethoxyquin diets were completely and partially protective, respectively, against the PA-induced lethality. The deaths were associated with severe hemorrhagic lesions in liver with or without hepatocytic necrosis. Both BHA and ethoxyquin significantly reduced the incidence of the hemorrhagic lesions but not the necrotic lesions in liver. Cysteine had no significant effect on either mortality or the liver lesions induced by the mixed PAs. These results suggest that dietary antioxidants have differential protective effects against lethality and acute hepatotoxicity induced by mixed PAs from tansy ragwort.

Animals↗

Comparison of two methods for teaching advanced arrhythmias to nurses.

An experimental study to compare the effectiveness of assisted self-directed learning (ASD) and traditional lecture methods (TLM) in acquiring competency for electrocardiogram interpretation was conducted within a conceptual framework of developmental and adult learning theory (Erickson, Tomlin & Swain, 1983; Knowles, 1980). After two teaching units were designed and an EKG posttest was constructed (r = .75) from actual patient records, registered nurse volunteers (N = 19) were randomly assigned to groups for simultaneous instruction. Because of the small sample size, statistical procedures were used to determine the effectiveness of randomization and to justify statistical procedures. EKG post-test scores for the experimental group (ASD, M = 81) and the control group (TLM, M = 71) were significantly different (one-tailed t = 1.79; p = .045); however, participants' prior knowledge of basic arrhythmias was not independent of method (ANCOVA, F[1, 16] = 21.373, p = .0003, covariate; F[1.16] = 2.312, p = .1479, main effects). EKG post-test scores were not related to critical care experience, cardiac monitoring experience, education level, or course satisfaction. While both methods are effective, ASD had higher mean scores and is more cost- and time-efficient.

Arrhythmias, Cardiac↗