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Biomedical subjects

J E Gibson

Publications and source records attributed to J E Gibson.

At least 55 records · Page 3Linked to original sources
PubMed1976

Effects of cyclophosphamide treatment of newborn mice on the development of swimming and reflex behavior and on adult behavioral performance.

Cyclophosphamide (CP), an antineoplastic agent, was administered subcutaneously to Swiss-Webster mice on the day of birth and the mice were later tested for developmental or adult behavioral abnormalities. The CP dosages of 20, 30, or 45 mg/kg of body weight retarded maturation of swimming ability and 45 mg/kg retarded maturation of the righting reflex. At 7 weeks of age mice treated neonatally with 30 or 45 mg/kg of CP had reduced locomotor activity and were more emotionally reactive than controls in an open field. Mice treated with 30 but not 20 mg/kg of CP tended to avoid shock less than controls and those treated with 20 mg/kg fell more frequently when crossing a rotating rod for food. Rotorod performance was improved by treatment with 45 but not 30 mg/kg of CP. All dosages examined decreased body weight gains but only 30 or 45 mg/kg resulted in gross body malformations. The results indicate that CP can functionally impair the development of mice and that some of these impairments are independent of gross body malformations.

Abnormalities, Drug-Induced↗
PubMed1976

Perinatal nephropathies.

The purpose of this paper is to review the development of the mammalian kidney and to assess the influence that various perinatal manipulations may have on the developmental process either morphologically or functionally. Immature kidneys in general have less functional capacity than adult kidneys and a low rate of glomerular filtration, perhaps related to renal blood flow, which appears to limit the disposition of a fluid or solute load. Tubular reabsorption is also limited leading to the urinary loss of glucose, amino acids, bicarbonate and phosphate. Although the relatively low function of the immature kidney is a normal part of development, its capacity to respond under conditions of stress may be less adequate than in adults. An additional concern is that a variety of perinatal manipulations, such as the incidental or accidental ingestion of a chemical, may lead to varying degrees of altered morphogenesis or functional development of the kidney. Chemical induced renal anomalies may be of several types, but in typical teratology experiments hydronephrosis may be the most frequent observation. The functional consequences of these renal malformations may be lethal or inconsequential or while an animal may be able to survive and develop normally in the presence of a renal malformation, it is possible that a stressful situation would unmask a functional malformation which could compromise survival. Thus, some renal abnormalities may be subtle enough to go unnoticed without experimental tests. Without such tests it is impossible to evaluate the effect of functional alterations on successful adaptation.

Abnormalities, Drug-Induced↗
PubMed1976

Paraquat toxicity: proposed mechanism of action involving lipid peroxidation.

The purpose of this study was to investigate the hypothesis that paraquat pulmonary toxicity results from cyclic reduction-oxidation of paraquat with sequential generation of superoxide radicals and singlet oxygen and initiation of lipid peroxidation. In vitro mouse lung microsomes catalyzed an NADPH-dependent, single-electron reduction of paraquat. Incubation of paraquat with NADPH, NADPH-cytochrome c reductase, and purified microsomal lipid increased malondialdehyde production is a concentration dependent manner. Addition of either superoxide dismutase or a single oxygen trapping agent 1,3-dipheylisobenzo furan inhibited paraquat stimulated lipid peroxidation. In vivo, pretreatment of mice with phenobarbital decreased paraquat toxicity, possibly by competing for electrons which might otherwise reduce paraquat. In contrast, paraquat toxicity in mice was increased by exposure to 100% oxygen and by deficiencies of the antioxidants selenium, vitamin E, or reduced glutahione (GSH). Paraquat, given IP to mice, at 30 mg/kg, decreased concentrations of the water-soluble antioxidant GSH in liver and lipid soluble antioxidants in lung. Oxygen-tolerant rats, which hae increased activities of pulmonary enzymes which combat lipid peroxidation, were also tolerant to lethal doses of paraquat as indicated by an increased paraquat LT50. Furthermore, rats chronically exposed to 100 ppm paraquat in the water had elevated pulmonary activities of glucose-6-phosphate dehydrogenase and GSH reductase. These results were consistent with the hypothesis that lipid peroxidation is involved in the toxicity of paraquat.

Anaerobiosis↗
PubMed1976

Effects of chronic administration of polybrominated biphenyls on parameters associated with hepatic drug metabolism.

Parameters relating to hepatic microsomal drug metabolism were measured in vitro following 2 weeks exposure of rats to polybrominated biphenyls (PBB) as a dietary supplement at 4.69, 18.75, 75 and 300 ppm. The mixture of PBB was a potent inducer of hepatic microsomal drug metabolism. The pattern of induction seen after PBB exposure was compared with that produced by phenobarbital and 3-methyl-cholanthrene and the pattern of induction observed shared similarities with both of these agents.

Animals↗
PubMed1976

Effect of paraquat (methyl viologen) on liver function in mice.

Paraquat poisoning may result in pulmonary damage and hepatotoxicity. To examine the effect of paraquat on liver function, paraquat-treated mice were injected with sulfobromophthalein (BSP, 100 mg/kg) or indocyanine green (20 mg/kg) via the tail vein and plasma concentrations of these compounds were determined at various times. Hepatic concentrations of reduced glutathione were also determined following paraquat. Retention of BSP and indocyanine green in the plasma was observed 24 hours after paraquat. Body temperature of the poisoned mice was significantly depressed 24 hours after treatment and the paraquat-induced indocyanine green retention could be reversed by warming the paraquat-treated mice to normal body temperature. In contrast, paraquat-induced BSP retention was independent of body temperature. Inasmuch as hepatic glutathione concentrations were reduced 24 hours after paraquat treatment, the retention of BSP in the plasma may have been secondary to the reduction of hepatic glutathione concentrations.

Animals↗
PubMed1975

Effects in mice of high and low environmental temperature on the maternal and fetal toxicity of 2-sec-butyl-4,6-dinitrophenol (dinoseb) and on disposition of [14C]-dinoseb(12).

Swiss-Webster female mice were treated with 2-sec-butyl-4,6-dinitrophenol (dinoseb) and maintained in an increased environmental temperature (32 degrees C) for 24 h or a decreased temperature (0-6 degrees C) for 1.5-4 h. In two experiemtns animals maintained at low temperature were kept wet during the cold exposure, to enhance the reduction in body temperature, by rinsing them with water at approximately 30 min intervals. Results from nonpregnant females indicated that increased temperature lowered the LD50 for single injections of dinoseb from 20.2 to 14.1 mg/kg and that reduced temperature for 4 h had no effect on the LD50. A 24 h exposure to 32 degrees C enhanced the effect of 3 daily dinoseb treatments of pregnant mice; it increased maternal mortality, decreased fetal body weight, and increased frequency of fetal anomalies. Fetal body weight and the frequency of malformations were the same in groups exposed to low temperature and maintained at room temperature. Disposition of [14 C] dinoseb was also determined in nonpregnant mice exposed to temperatures of 0, 24, and 32 degrees C. The periods of environmental temperature studied (3-24 h) had no effect on the rate of disappearance of dinoseb from plasma or other tissues examined.

Animals↗
PubMed1975

Lipid peroxidation: a possible mechanism for paraquat toxicity.

The toxicity of the herbicide paraquat in mice, measured by the single dose lethal to 50 per cent of the animals after 7 days, was significantly enhanced by prior exposure to diets deficient in selenium or vitamin E and by pretreatment with diethyl maleate. These data suggest lipid peroxidation to be an important in vivo biochemical mechanism of paraquat toxicity as both selenium and vitamin E have antioxidant functions.

Animals↗