Effect of 18 HR fast and glutathione depletion on 1,1-dichloroethylene-induced hepatotoxicity and lethality in rats

Jaeger, Rudolph J.; Conolly, Rory B.; Murphy, Sheldon D.

doi:10.1016/0014-4800(74)90053-7

Cited by 141 publications

(31 citation statements)

References 11 publications

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“…In our earlier studies we found that inhalation exposure to 1,1-DCE was uniformly hepatotoxic and fatal to fasted rats at concentrations which were not fatal or hepato-toxic to fed rats (1). In an attempt to elucidate the reasons for this enhanced response in fasted animals, biochemical comparisons were made between the two nutritional states (i.e., fed vs. fasted), and it was observed that glutathione (GSH) content was diminished in the livers from fasted rats.…”

Section: Introductionmentioning

confidence: 87%

“…Inhalation exposures were conducted as previously described (1,6) by using the dynamic inhalation chamber described by Leach (7). Determinations of chamber concentrations were made gas chromatographically using a Varian-1700 (1).…”

Section: Methodsmentioning

confidence: 99%

“…Glutathione concentrations and serum enzyme activities were determined (1,6). Tests of significance were done either parametrically when the F ratio indicated that this was permissable or nonparametrically.…”

Section: Methodsmentioning

confidence: 99%

“…From this, an initial hypothesis was developed which postulated glutathione as a site of detoxification of 1,1-DCE. When this hypothesis was tested, both in vivo and in the isolated perfused rat liver, it was found that those animals with a diminished hepatic glutathione concentration were significantly more susceptible to 1,1-DCE exposure (1).…”

Section: Introductionmentioning

confidence: 99%

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Biochemical toxicology of unsaturated halogenated monomers.

Jaeger¹,

Conolly²,

Reynolds³

et al. 1975

Environ Health Perspect

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Previous inhalation toxicity studies from our laboratory have shown that 1,1-dichloroethylene (1,1-DCE), 1,1-dibromoethylene (1,1-DBE), and 2-chloro-1,3-butadiene (2-CBD) are more toxic to fasted rats than to fed rats. Vinyl chloride monomer (VCM) and 1,1-difluoroethylene (1,1-DFE) were not acutely hepatotoxic at 46,500 and 82,000 ppm, respectively, in normal male rats, whether fed or fasted. On a molar basis, 1,1-DBE and 1,1-DCE have similar toxicities while 2-CBD is less toxic. All three compounds produce similar elevation of serum transaminase and bloody ascites, although at differing times following differing exposure concentrations.1,1-DCE produces massive midzonal hepatic necrosis with hepatic thrombosis and chromatolysis within 2 hr after a 4 hr exposure of fasted rats to 200 ppm. Subsequent to formation of this midzonal lesion, the central portion of the lobule collapses, accompanied by congestion, ascites, and an increased hematocrit in the rat. Serum transaminase and sorbital dehydrogenase are greatly elevated at 6 hr. This effect in fasted rats is associated with glutathione (GSH) depletion. Diethyl maleate (DEM) which depletes GSH in fed rats potentiates the injury associated with 1,1-DCE exposure as well as that produced by 2-CBD. Rats fed ad libitum and exposed to 1,1-DCE or 2-CBD at night, a time of low hepatic GSH concentration, exhibit enhancement of hepatotoxic response when compared to animals exposed during the day when GSH is high.

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Section: Introductionmentioning

confidence: 87%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biochemical toxicology of unsaturated halogenated monomers.

Jaeger¹,

Conolly²,

Reynolds³

et al. 1975

Environ Health Perspect

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“…Concentrations of VCM were adjusted and monitored by gas chromatography (9). For morphologic examination of the liver, animals were anesthetized with pentobarbital 24 hr after the beginning of a single exposure, or immediately after the fifth exposure, portal veins were cannulated, and the liver was briefly perfused with Ringer's lactate containing Isuprel, 1 mg/l., at 37°C, followed by buffered 1%o glutaraldehyde.…”

Section: Methodsmentioning

confidence: 99%

Acute Liver Injury by Vinyl Chloride: Involvement of Endoplasmic Reticulum in Phenobarbital-Pretreated Rats

Reynolds¹,

Jaeger²,

Murphy³

1975

Environmental Health Perspectives

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A single 6-hr exposure to vinyl chloride monomer (5%o) produces extensive vacuolization of centrolobular liver parenchyma and focal midzonal necrosis in the hepatic lobuole in phenobarbital-pretreated rats. Ultrastructurally, vacuolization consists of dilation of cysternae of rough endoplasmic reticulum and in the same cells smooth endoplasmic reticulum coalesces into discreet aggregates resembling denatured membranes. The findings support the hypothesis that vinyl chloride is hepatotoxic because it is converted into a toxic metabolite by components of the mixed function oxidase system of liver endoplasmic reticulum.

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Conjugation of glutathione with the reactive metabolites of 1,1-dichloroethylene in murine lung and liver

Forkert¹

1997

Microsc. Res. Tech.

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Effect of 18 HR fast and glutathione depletion on 1,1-dichloroethylene-induced hepatotoxicity and lethality in rats

Cited by 141 publications

References 11 publications

Biochemical toxicology of unsaturated halogenated monomers.

Biochemical toxicology of unsaturated halogenated monomers.

Acute Liver Injury by Vinyl Chloride: Involvement of Endoplasmic Reticulum in Phenobarbital-Pretreated Rats

Conjugation of glutathione with the reactive metabolites of 1,1-dichloroethylene in murine lung and liver

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