Biochemical changes in rat liver after administration of carbon disulphide, with particular reference to microsomal changes

Bond, E.J.; Matteis, Federico De

doi:10.1016/0006-2952(69)90368-2

Cited by 126 publications

(17 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This latter factor may be related to an increased breakdown of amino acids or to a transient inhibition of protein synthesis in the liver of CS2-treated rats (Bond and de Matteis, 1969). However, no accumulation of esterified fatty acid in total liver samples was observed in the present work, and in the absence of more detailed study of plasma triglyceride turnover after acute CS2-intoxication no further comment can be made.…”

Section: Discussioncontrasting

confidence: 56%

Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat.

Cunningham¹

1975

Occupational and Environmental Medicine

View full text Add to dashboard Cite

. Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat. The concentration of plasma free fatty acids in rats was significantly increased after a short period of exposure to inhalation of carbon disulphide (4 h, 2 mg/i). In contrast, after a longer period of exposure (15 h overnight, 2 mg/i) the concentration of plasma free fatty acid was significantly decreased despite a small hypoglycaemia. At the same time plasma urea concentration was significantly higher in CS2-treated rats. The total esterified fatty acid content of plasma was lower after exposure, but there was no change in plasma glycerol. Following an intragastric water load, no differences were observed in urine flow rate nor in renal clearances of urea and inulin between control and treated rats. It is concluded that the rate of urea production is significantly increased during acute CS2-intoxication, and it is suggested that two factors contribute to this effect: first, an increased breakdown of proteins with which CS2 or its metabolic products have reacted; and secondly an increased rate of utilization of plasma glucose associated with increased gluconeogenesis from amino acid precursors. It is further suggested that the stress effects of CS2 dominate in the short term before being overcome by a diminished sympathetic response. When rats were exposed to CS2 overnight without free access to water, the great vessel haematocrit was significantly lower than in corresponding controls. This was shown to be accounted for by differences in plasma volume. No such difference was observed when rats had free access to water during exposure. These effects probably reflect differing rates of water loss under mildly dehydrating conditions, but a direct effect of CS2 on the cardiovascular system is not excluded.

show abstract

Section: Discussioncontrasting

confidence: 56%

Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat.

Cunningham¹

1975

Occupational and Environmental Medicine

View full text Add to dashboard Cite

show abstract

“…A variety of functional groups that either occur naturally or have been specifically engineered into drugs to increase their stability, solubility, or bioavailability have been shown to predispose these drugs to metabolism by a particular P450 isozyme or isozymes in such a way as to generate reactive intermediates that can lead to MBI by one or more of the previously mentioned routes These molecules can be grouped according to their structural aspects and they fall into a number of major categories including: (a) various sulfur-containing compounds (eg, carbon disulfide [281][282][283], diethyldithiocarbamate [284], isothiocyanates [285], mercaptosteroids [286][287][288][289][290][291][292][293], parathion [294,295], thioureas [296], thiophenes [297], and tienilic acid [298]; (b) various halogen containing compounds such as chloramphenicol [299][300][301][302], N-monosubstituted dichloroacetamides [303], and N(2-p-nitrophenethyl) dichloroacetamide [304]; (c) acetylenes and alkyl and aryl olefins [305][306][307][308][309][310][311] [328][329][330][331][332][333][334][335][336], and the furanopyridine, L-75...…”

Section: Covalent Binding To the P450 Proteinmentioning

confidence: 99%

Inhibition of Cytochrome P450 Enzymes

Correia

Hollenberg

2015

Cytochrome P450

View full text Add to dashboard Cite

“…While the significance of this finding cannot yet be properly assessed, it is recorded and discussed briefly since it suggests that exposure of people to drugs or other chemicals might alter their response to CS2. The biochemical changes induced in the liver by single doses of CS2 are described in detail elsewhere (Bond and de Matteis, 1969).…”

mentioning

confidence: 99%

Effects of carbon disulphide on the liver of rats

Bond

Butler

Matteis

et al. 1969

Occupational and Environmental Medicine

View full text Add to dashboard Cite

. (1968). Brit. J. industr. Med., 26,[335][336][337] Effects of carbon disulphide on the liver of rats. Normal rats surviving a single oral dose of carbon disulphide (CS2) show liver enlargement and depression of drug-metabolizing enzymes but no liver necrosis. If the drug-metabolizing enzymes are stimulated by phenobarbitone before exposure to CS2, the LD50 does not change but liver necrosis is produced.The toxic effects of carbon disulphide (CS2) are well known and affect mainly the central and peripheral nervous systems, in some cases after damage to blood vessels. There is very little published work on the effects of CS2 on experimental animals, and no generally accepted idea on its precise mode of action (Brieger and Teisinger, 1967). It is known that CS2 is partly metabolized to dithiocarbamates, and conversely dithiocarbamates such as disulfiram (Antabuse) may be partly metabolized to release CS2. What role the metabolites play in initiating the pathological lesions is unknown. This paper records the observations that pretreatment with a drug (phenobarbitone), which stimulates liver microsome enzyme activity, significantly alters the degree of liver cell damage produced by CS2. While the significance of this finding cannot yet be properly assessed, it is recorded and discussed briefly since it suggests that exposure of people to drugs or other chemicals might alter their response to CS2. The biochemical changes induced in the liver by single doses of CS2 are described in detail elsewhere (Bond and de Matteis, 1969). overnight before being given by mouth CS2 1:1 in arachis oil. Control rats received arachis oil only.Pretreatment by phenobarbitone involved two doses, six hours apart, of 50 mg./kg. two days before and a single dose of 80 mg./kg. one day before the CS2. The drug, 2-diethylaminoethyl 2,2-diphenylbutyrate (SKF 525A), was used to depress the drug-metabolizing enzymes stimulated by phenobarbitone, and for this purpose 40 mg./kg. was given intraperitoneally 45 minutes before the carbon disulphide. At autopsy tissues from the major organ were fixed in 10% formol saline. Paraffin sections were prepared in the usual fashion and stained with Harris's haematoxylin and eosin. Frozen sections were stained with oil red 0 for fat. ResultsRats killed 24 hours after a dose of 1 ml./kg. CS2 often had stomachs somewhat dilated with clear fluid, and might show moderate congestion with some haemorrhages into the lungs. The other organs appeared normal, and histologically no changes were found in the kidneys, spleen, pancreas, heart or adrenals. The liver weight of these animals was greater than that of fasted controls, but histologically little change was seen except for an increase in fat in the periportal zone. In the centrilobular zone of one animal a few cells with pyknotic nuclei and dense eosinophilic cytoplasm were present, but at no time was a zonal necrosis seen. In the remaining animals this change was not seen (Fig. 1). At a dose of 0-5 ml./kg. no histological change was seen in the liver. Rats pretr...

show abstract

Biochemical changes in rat liver after administration of carbon disulphide, with particular reference to microsomal changes

Cited by 126 publications

References 24 publications

Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat.

Effects of a single exposure to carbon disulphide on the rate of urea production and on plasma free fatty acid and glucose concentrations in the rat.

Inhibition of Cytochrome P450 Enzymes

Effects of carbon disulphide on the liver of rats

Contact Info

Product

Resources

About