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Biomedical subjects

J A Castro

Publications and source records attributed to J A Castro.

At least 181 records · Page 10Linked to original sources
PubMed1981

Studies on the mechanism of enhancement of carbon tetrachloride hepatotoxicity by Triton WR 1339.

Pretreatment of rats with Triton WR 1339 significantly enhanced the intensity of CC14-induced liver necrosis. Previous workers suggested that this effect might be due to enhancement by Triton WR 1339 of cellular degradative processes. This pretreatment, however, also enhanced the intensity of covalent binding of [14C]CC14 metabolites to microsomal protein at 3 or 6 h, but not 1 h after its administration. This effect is not due to changes of microsomal P-450 content or increased activity of mixed-function oxygenase-metabolizing drugs like pentobarbital. Pretreatment with Triton WR 1339 also partially increased CC14-induced peroxidation of microsomal lipids at 1, 3 or 6 h after administration of the hepatotoxin. Liver concentrations of CC14 in Triton WR 1339-treated rats were significantly higher at 3 or 6 h but not at 1, 10 or 24 after its i.p. administration. Triton WR 1339 treatment decreased the body temperature of the rats and further intensified the decrease produced by CC14. Results suggest that, in addition to possible effects of Triton WR 1339 administration on liver-cell degradative processes, there are other actions of this detergent on CC14 activation and lipid peroxidation which might play a role in the heightened response of the liver of CC14-induced injury.

Animals↗
PubMed1980

Effect of different chemicals on thioacetamine-induced liver necrosis.

Several inhibitors of cytochrome P-450 mediated oxidative transformations, ethyl 2-diethylaminoethyl-2-phenyl-2-ethylmalonate, ethyl-2-diethyl-aminoethyl-2-ethyl-2-buthylmalonate, 2,4 dichloro-6-phenoxyethyl diethylamine, 2-diethylaminoethyl-2-phenyl- (2-propene)-4-penten-1-oate or 3-amino,1,2,4 triazole were not able to significantly prevent thiocetamide induced necrosis at 24 h as evidenced by isocitric acid dehydrogenase activity or histologically. In contrast, several other sulfur containing compounds, tetraethyl thiuramidisulfide, diethyldithiocarbamic acid, thiourea or 1-methyl-2-mercaptoimidazole, which are inhibitors of non-cytochrome P-450 dependent amine oxidase systems, significantly prevented thioacetamide induced liver necrosis at 24 h. Notwithstanding, diphenhydramine, nicotinamide, trimethylamine and imipramine, which are substrates of this amino oxidase system, do not protect. All the chemicals tested prolonged the pentobarbital sleeping time, but there is no correlation between the intensity of this effect and their ability for preventing thioacetamide liver necrosis. These observations suggest that cytochrome P-450 does not play a major role in the activation of thioacetamide to a proximal or an ultimate necrogenic metabolite. Other microsomal enzymes metabolizing sulfur compounds could be involved in the major activation process.

Acetamides↗
PubMed1980

Covalent binding of chloroform metabolites to nuclear proteins - no evidence for binding to nucleic acids.

No evidence was found for covalent binding of CHCl3 metabolites to male Sprague-Dawley rats or strain A/J male mice liver DNA or RNA under different experimental conditions including phenobarbital or 3-methyl-cholanthrene or diethylmaleate treatments or multiple CHCl3 injections. In addition, no binding to DNA was observed when DNA was exposed to CHCl3 in incubation mixtures containing microsomes and NADPH or when tissue slices were incubated with CHCl3. In contrast, nuclear histone and non-histone proteins bound to CHCl3 metabolites.

Animals↗
PubMed1980

Evidence against the formation of malondialdehyde derived fluorescent products in rat liver during carbon tetrachloride poisoning.

Aerobic incubation of microsomal suspensions led to the formation of malondialdehyde derived fluorescent products, which were not formed in the presence of EDTA or antioxidants as propyl gallate. Malondialdehyde (MA) occurrence in livers from rats or A/J mice accutely or chronically intoxicated with CCl4 was not detected using the spectrofluorometric procedure.

Animals↗
PubMed1980

Studies on the prevention of CCl4 induced liver necrosis by agents having effects on cell membrane.

Nupercaine, promazine and benadryl partially prevented liver injury produced by CCl4 given orally, 24 hours after administration, in contrast to cetyl trimethyl ammonium bromide and anthisan which did not show any effect. Only benadryl and anthisan were able to partially prevent liver damage at 24 hours caused by ip administration of CCl4. None of these compounds decreased CCl4 content in liver at 1; 3 or 6 hours after oral CCl4 administration. Results suggest that benadryl could prevent liver necrosis, changing the cell response to injury by CCl4.

Administration, Oral↗
PubMed1980

Nuclear activation of carbon tetrachloride and chloroform.

Highly purified rat liver nuclear preparations are able to activate anaerobically CCl4 and aerobically CHCl3 to reactive metabolites that bind to lipids and proteins. Activity in nuclear preparations is smaller than in microsomes but of the same order of magnitude.

Aerobiosis↗
PubMed1980

Reactions of trichloromethyl free radicals with aminoacids.

Trichloromethyl free radicals produced from CCl4 in a benzoyl-peroxide catalyzed chemical reaction are able to interact with several aminoacid esters. Yhe interaction is relatively more intense with cystine, tyrosine and tryptophan. In most cases it was possible to separate at least one reaction product from unreacted aminoacid ester by TLC.

Amino Acids↗
PubMed1980

Promethazine administration to rats and CCl4 induced lipid peroxidation of liver microsomal lipids.

Promethazine inhibited CCl4 stimulated microsomal lipid peroxidation in vitro at concentrations ranging from 10(-3) to 10(-8)M. CCl4 administered to rats at a dose of 1 ml/kg decreased the arachidonic acid content of microsomal lipids after 6 hours of intoxication. Prior promethazine treatment, at dosage regimes that preclude CCl4 induced liver necrosis at 24 hours, did not significantly prevent the CCl4 induced decrease in arachidonic acid content. Moreover, promethazine itself produced a similar decrease but in complete absence of liver damage. Results suggest that either lipid peroxidation is not relevant to liver injury or that the arachidonic acid decrease in microsomal lipids is not evidence for lipid peroxidation occurrence or that promethazine effects are not related to inhibition of lipid peroxidation.

Animals↗
PubMed1980

Pyrazole prevention of CC14-induced ultrastructural changes in rat liver.

Carbon tetrachloride (CC14) administration to rats leads to an early dilatation, vesiculation and disorganization of the liver endoplasmic reticulum (ER). This hepatotoxin also causes detachment of ribosomes from ER membranes, dilatation of the Golgi cisternae and occasionally dilatation of the perinuclear membrane. Prior treatment of the rats with pyrazole completely prevents CC14- induced ultrastructural alterations observed in liver at 3 h. This drug is known to decrease the intensity of the irreversible binding of CC14 reactive metabolites to cellular constituents without modifying the intensity of the CC14- induced lipid peroxidation, either in vitro or in vivo, as measured by the diene conjugation procedure or by decreases inthe arachidonic acid content of microsomal phospholipids. Results suggest that interaction of reactive metabolites rather than lipid peroxidation mediates deleterious effects of CCl4 on the liver ER.

Animals↗
PubMed1978

Early destruction of cytochrome P-450 in testis of carbon tetrachloride poisoned rats.

There is 20--36 percent decrease in the microsomal cytochrome P-450 (P450) content of the testes 3 or 6 h after CCl4 administration to Sprague--Dawley male rats. Irreversible binding of CCl4 metabolites to testicular microsomal lipids is observed as early as 3 h while CCl4 induced lipid peroxidation does not occur within the first 6 h of poisoning. Results suggest that reactive metabolites rather than lipid peroxidation is involved in P-450 destruction in the testes.

Animals↗
PubMed1978

Carbon tetrachloride induced ultrastructural alterations in pancreatic acinar cells and in the hepatocytes. Similarities and differences.

We found that 14C from 14CCl4 gets covalently bound to rat pancreas and liver microsomal lipids. The intensity of this process in 320 times smaller in the former than in the latter organ. We did not detect any cytochrome P-450 (P-450) or ethylmorphine N-demethylase activity in pancreatic microsomes in contrast to the high content of those components occurring in liver. Similarly, CCl4 induced lipid peroxidation is observed in liver preparations but not in pancreas. There was no evidence for any histological alterations in pancreas 24 h after administration of a toxic dose causing marked cnetrolobular necrosis in liver. CCl4 causes profound ultrastructural alterations in the hepatocytes involving early the endoplasmic reticulum, the Golgi complex and the nuclear envelope and later the entire cell. In selected clones of pancreatic acinar cells we observed an intense dilatation in the rough endoplasmic reticulum and polysome detachment from their membranes, the appearance of myelin figures and occasionally of large autophagic vacuoles. No alterations in other organelles were detected but a slight increase in the number of lipid droplets was observed. CH2Cl2 did not behave similarly.

Amylases↗