Effect of fasting, diethyl maleate, and alcohols on carbon tetrachloride-induced hepatotoxicity

Harris, Richard N.; Anders, M.W.

doi:10.1016/0041-008x(80)90289-6

Cited by 54 publications

(7 citation statements)

References 28 publications

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“…injection of mice with 1.6 g of CCl 4 /kg. Harris and Anders (1980) have demonstrated that marked (i.e., 83%) depletion of liver GSH by diethyl maleate potentiated CCl 4 hepatotoxicity in S-D rats. The diurnal NPSH decreases we observed (i.e., ϳ30%) were less pronounced.…”

Section: Mechanisms Of Circadian Rhythmicity Of CCL 4 Hepatotoxicity 277mentioning

confidence: 99%

“…Mitchell et al (1985) observed marked enzyme leakage from primary cultures of rat hepatocytes when GSH was reduced below a threshold of 20% of control, irrespective of the chemical used to deplete GSH. Harris and Anders (1980) noted that fasted rats exhibited liver injury that was twice as severe as their diethyl maleate-pretreated counterparts, indicative of involvement of other factors. Our own results demonstrate that CYP2E1 induction is an important factor in fasting-elicited and in diurnal changes in susceptibility of rats to CCl 4 .…”

Section: Mechanisms Of Circadian Rhythmicity Of CCL 4 Hepatotoxicity 277mentioning

confidence: 99%

“…Volatile organic compounds (VOCs) are a class of solvents to which many people are exposed occupationally and environmentally. Early studies of chloroform (Lavigne et al, 1983), carbon tetrachloride (CCl 4 ) (Harris and Anders, 1980;Bruckner et al, 1984), and 1,1-dichloroethylene (Jaeger et al, 1973) revealed circadian rhythms in susceptibility of rats to liver damage by the chemicals. Some of the investigators speculated that periods of enhanced susceptibility might be due to cyclic increases in metabolic activation of the VOCs.…”

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confidence: 99%

“…Fasting for 16 to 48 h is known to enhance the metabolism and hepatotoxicity of CCl 4 (Harris and Anders, 1980;Nakajima et al, 1982). Fasting has also been found to induce hepatic microsomal cytochrome P450IIE1 (CYP2E1) (Brown et al, 1995).…”

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confidence: 99%

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Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Bruckner

Ramanathan²,

Lee³

et al. 2002

J Pharmacol Exp Ther

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The toxicity of carbon tetrachloride (CCl 4 ) and certain other chemicals varies over a 24-h period. Because the metabolism of some drugs follows a diurnal rhythm, it was decided to investigate whether the hepatic metabolic activation of CCl 4 was rhythmic and coincided in time with maximum susceptibility to CCl 4 hepatotoxicity. A related objective was to test the hypothesis that abstinence from food during the sleep cycle results in lipolysis and formation of acetone, which participates in induction of liver microsomal cytochrome P450IIE1 (CYP2E1), resulting in a diurnal increase in CCl 4 metabolic activation and acute liver injury. Groups of fed and fasted male Sprague-Dawley rats were given a single oral dose of 800 mg of CCl 4 /kg at 2-to 4-h intervals over a 24-h period. Serum enzyme activities, measured 24 h post dosing as indices of acute liver injury, exhibited distinct maxima in both fed and fasted animals dosed with CCl 4 near the beginning of their dark/active cycle. Blood acetone, hepatic CYP2E1 activity, and covalent binding of 14 CCl 4 /metabolites to hepatic microsomal proteins in untreated rats fed ad libitum followed circadian rhythms similar to that of susceptibility to CCl 4 . Parallel fluctuations of greater amplitude were seen in rats fasted for 24 h. Hepatic glutathione levels were lowest at the time of greatest susceptibility to CCl 4 . Acetone dose-response experiments showed high correlations between blood acetone levels, CYP2E1 induction, and CCl 4 -induced liver injury. Pretreatment with diallyl sulfide suppressed CYP2E1 and abolished the circadian rhythmicity of susceptibility to CCl 4 . These findings provide additional support for acetone's physiological role in CYP2E1 induction and for CYP2E1's role in modulating CCl 4 chronotoxicity in rats.Many physiological and biochemical processes in laboratory animals and humans have been found to vary rhythmically over a 24-h period (i.e., to exhibit a circadian or diurnal rhythm). Rhythms are considered as sequences of biological events, repeating themselves in the same order and at the same intervals. Temporal differences in drug action and toxicity have been recognized for over 50 years in humans and in laboratory animals. A number of cyclic physiological processes can affect the absorption, distribution, metabolism, and elimination of drugs and other chemicals (Labrecque and Belanger, 1991).The chronotoxicity of solvents and other industrial chemicals has received relatively little attention. Volatile organic compounds (VOCs) are a class of solvents to which many people are exposed occupationally and environmentally. Early studies of chloroform (Lavigne et al., 1983), carbon tetrachloride (CCl 4 ) (Harris and Anders, 1980;Bruckner et al., 1984), and 1,1-dichloroethylene (Jaeger et al., 1973) revealed circadian rhythms in susceptibility of rats to liver damage by the chemicals. Some of the investigators speculated that periods of enhanced susceptibility might be due to cyclic increases in metabolic activation of the VOCs. Tempora...

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Section: Mechanisms Of Circadian Rhythmicity Of CCL 4 Hepatotoxicity 277mentioning

confidence: 99%

Section: Mechanisms Of Circadian Rhythmicity Of CCL 4 Hepatotoxicity 277mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Bruckner

Ramanathan²,

Lee³

et al. 2002

J Pharmacol Exp Ther

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“…Some mechanism studies have focused on rhythmic variations in drug disposition in cluding metabolism and excretion [Radzialowski and Bousquet, 1968;Jon et al" 1971; Lake el al., 1976], on changes in the sensitiv ity o f the target issue to a particular agent [Roberts et al, 1970;Nelson and Halberg, 1973;Bornschein et al, 1973;Wolfe et al, 1979;Deimling and Schnell, 1980], and on rhythms in the physiological levels o f endog enous substances such as glutathione [Beck et al, 1958;Jaeger et al, 1973;Hanson and Anders, 1978;Harris and Anders. 1980;Schnell et al, 1983], We have previously reported studies which described circadian rhythms in the toxicity of acetaminophen in male mice.…”

Section: Introductionmentioning

confidence: 99%

Factors Influencing Circadian Rhythms in Acetaminophen Lethality

et al. 1984

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Experiments were conducted to examine the effects of changes in lighting schedules and food consumption on circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice. Under a normal lighting schedule (light: 06.00–18.00 h), male mice exhibited a circadian rhythm in acetaminophen lethality (peak: 18.00 h; nadir: 06.00, 10.00 h) and an inverse rhythm in hepatic glutathione concentrations (peak: 06.00, 10.00 h; nadir: 18.00 h). Under a reversed lighting schedule (light: 18.00–06.00 h) the glutathione rhythm was reversed and the rhythm in acetaminophen lethality was altered showing greater sensitivity to the drug. Under continuous light, there was a shift in the acetaminophen lethality and the hepatic glutathione rhythms. Under continuous dark, both rhythms were abolished. Under a normal lighting regimen, hepatic glutathione levels were closely correlated with food consumption; i.e., both were increased during the dark phase and decreased during the light phase. Fasting the mice for 12 h abolished the rhythms in acetaminophen lethality and hepatic glutathione levels; moreover, the lethality was increased and the hepatic glutathione levels were decreased. These experiments show that both lighting schedules and feeding can alter the circadian rhythms in acetaminophen lethality and hepatic glutathione levels in male mice.

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Metabolic effects of acetaminophen. Studies in the isolated perfused rat liver

Itinose

Sakuno

Bracht

1989

Cell Biochemistry & Function

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The effects of acetaminophen on the metabolism of the isolated perfused rat liver were investigated. The following results were obtained: (1) Acetaminophen increased glucose release and glycolysis from endogenous glycogen (glycogenolysis). (2) Oxygen uptake, gluconeogenesis from either pyruvate or fructose and glycogen synthesis were inhibited. (3) In isolated rat liver mitochondria acetaminophen decreased state III and state IV respiration; it also decreased the ADP/O ratio and the respiratory control ratio. (4) The action of acetaminophen on glycogenolysis was not affected by N-acetylcysteine; this compound, however, increased glycogen synthesis. (5) The effects of acetaminophen are reversible. It was concluded that glycogen depletion by acetaminophen can be produced by two mechanisms. The first, as previously demonstrated by several workers, depends on irreversible binding of a reactive metabolite. The second, however, is reversible and depends primarily on an inhibition of mitochondrial energy metabolism.

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Effect of fasting, diethyl maleate, and alcohols on carbon tetrachloride-induced hepatotoxicity

Cited by 54 publications

References 28 publications

Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Mechanisms of Circadian Rhythmicity of Carbon Tetrachloride Hepatotoxicity

Factors Influencing Circadian Rhythms in Acetaminophen Lethality

Metabolic effects of acetaminophen. Studies in the isolated perfused rat liver

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