dieldrin and Chemical-and-Drug-Induced-Liver-Injury

Topics: Adipose Tissue; Aldrin; Animals; Central Nervous System Diseases; Chemical and Drug Induced Liver Injury; Chlordan; DDT; Dieldrin; Dogs; Drug Synergism; Endrin; Environmental Pollution; Female; Heptachlor; Hexachlorocyclohexane; Humans; Hydrocarbons, Halogenated; Malaria; Male; Methoxychlor; Mice; Mice, Inbred Strains; Pesticides; Rats; Rats, Inbred Strains; Reproduction; Toxaphene; Typhus, Epidemic Louse-Borne

Persistent organic pollutants (POPs) are degradation-resistant anthropogenic chemicals that accumulate in the food chain and in adipose tissue, and are among the most hazardous compounds ever synthesized. However, their toxic mechanisms are still undefined. To investigate whether characteristic molecular signatures can discriminate individual POP and provide prediction markers for the early detection of POPs exposure in an animal model, we performed transcriptomic analysis of rat liver tissues after exposure to POPs. The six different POPs (toxaphene, hexachlorobenzene, chlordane, mirex, dieldrin, and heptachlor) were administered to 11-week-old male Sprague-Dawley rats, and after 48 h of exposure, RNAs were extracted from liver tissues and subjected to rat whole genome expression microarrays. Early during exposure, conventional toxicological analysis including changes in the body and organ weight, histopathological examination, and blood biochemical analysis did not reflect any toxicant stresses. However, unsupervised gene expression analysis of rat liver tissues revealed in a characteristic molecular signature for each toxicant, and supervised analysis identified 2708 outlier genes that discerned the POPs exposure group from the vehicle-treated control. Combination analysis of two different multiclassifications suggested 384 genes as early detection markers for predicting each POP exposure with 100% accuracy. The data from large-scale gene expression analysis of a different POP exposure in rat model suggest that characteristic expression profiles exist in liver hepatic cells and multiclassification of POP-specific molecular signatures can discriminate each toxicant at an early exposure time. The use of these molecular markers may be more widely implemented in combination with more traditional techniques for assessment and prediction of toxicity exposure to POPs from an environmental aspect.

Topics: Animals; Chemical and Drug Induced Liver Injury; Dieldrin; Environmental Pollutants; Fungicides, Industrial; Heptachlor; Hexachlorobenzene; Insecticides; Liver; Male; Mirex; Pesticides; Rats; Rats, Sprague-Dawley; Toxaphene; Toxicity Tests; Transcriptome

The purpose of this study was to evaluate the protective effects of fenugreek (Trigonella foenum graecum L.) upon dieldrin-induced perturbations of haematological parameters and damages to liver and kidney of male Wistar rats. Under our experimental conditions, dieldrin poisoning resulted in 1) an alteration of several haematological parameters, 2) an oxidative stress evidenced by an increase of lipids peroxidation level associated with an increase of superoxide dismutase activity and a decrease of glutathione peroxidase and catalase activities in hepatic and renal tissues, 3) increased levels of glucose, total cholesterol, triglycerides, creatinine, urea, uric acid and proteins in blood, 4) increased activities of lactate dehydrogenase, alkaline phosphatase and transaminases in blood. Previous administration of fenugreek was found to hinder these dieldrin-induced damages: all hematological, renal and hepatic biomarkers, level of lipids peroxidation and activities of catalase and glutathione-peroxidase in liver and kidney were kept close to control values. This protective effect is mainly attributed to antioxidant properties of fenugreek.

Topics: Animals; Chemical and Drug Induced Liver Injury; Cholinesterase Reactivators; Dieldrin; Hydrocarbons, Chlorinated; Kidney; Kidney Diseases; Liver; Male; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; Reactive Oxygen Species; Treatment Outcome; Trigonella

The current study deals with the effect of the organochlorine insecticide on the liver of Wistar rats. The dieldrin effect on rats was tested after a single intraperitoneal (i.p.) injection of two doses: 3 and 6 mg/kg and observations were made 4 days later. Animals showed a significant dose-dependent increase in relative liver weight. Elevations of transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]), bilirubin and total activity of lactate dehydrogenase (LDH) were recorded in the sera of treated rats. Serum LDH-5 isoenzyme activity increases in a dose-dependent manner. In contrast, LDH-1 activity does not show any significant variations with respect to controls. Histological examination of the liver of dieldrin-treated animals revealed cytoplasmic vacuolation, focal necrosis and nuclear enlargement of hepatocytes. This study suggests that biochemical assessment (transaminases, LDH and bilirubin activity) and LDH (LDH-1 & LDH-5) isoenzyme profiles can be very helpful in defining the border of the liver injury, dieldrin damaged liver would be a valuable addition to histological analysis in evaluating histopathological liver changes.

Topics: Alanine Transaminase; Analysis of Variance; Animals; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Dieldrin; Dose-Response Relationship, Drug; Female; Injections, Intraperitoneal; Insecticides; Lactate Dehydrogenases; Liver; Male; Organ Size; Rats; Rats, Wistar; Spectrophotometry

The effect of vitamin E on dieldrin-induced hepatic focal lesion growth in male B6C3F1 mice previously treated with diethylnitrosamine (DEN) was investigated. After hepatic focal lesions were formed, mice were placed into one of the following treatment groups: Group 1, 50 mg vitamin E/kg diet (control NIH-07 diet); Group 2, 10 mg dieldrin/kg NIH-07 diet; Group 3, 10 mg dieldrin and 450 mg vitamin E/kg NIH-07 diet; and Group 4, 450 mg vitamin E/kg NIH-07 diet. Mice were killed and necropsied after 30 and 60 d of dietary treatment. The effect of treatment on lesion growth was examined by measuring the number of focal lesions per liver and the relative hepatic focal lesion volume. In addition, the possible cellular mechanism of focal hepatocyte growth was investigated by examining both focal DNA synthesis and apoptosis. Dieldrin treatment alone (Group 2) increased the focal lesion volume, focal lesion number, and focal lesion labeling index. Supplementation with vitamin E (Group 3) blocked this effect. Vitamin E supplementation to the diet alone (Group 4) also enhanced focal lesion growth and increased the number of lesions per liver, the relative focal volume, and the labeling index in hepatic focal lesions. Interestingly, vitamin E supplementation inhibited apoptosis in normal liver but did not produce an observable decrease in apoptosis in hepatic focal lesions. The present study showed that dieldrin (Group 2) or vitamin E supplementation alone (Group 4) promoted the growth of hepatic focal lesions in mice. However, when vitamin E is supplemented to dieldrin-fed mice (Group 3), there is an inhibition of hepatic focal lesion growth.

Topics: Animals; Apoptosis; Carcinogens; Chemical and Drug Induced Liver Injury; Dieldrin; Insecticides; Liver; Liver Diseases; Male; Mice; Precancerous Conditions; Vitamin E

The development of hyperplastic and neoplastic lesions of parenchymal cells of the liver adjacent to central veins was observed in C3H mice ingesting the chlorinated hydrocarbons, dieldrin or aldrin, in the diet. Lesions could be followed from pericentral hyperplasia to areas of hyperplasia, nodules of hyperplasia, small hepatocellular carcinomas, and large well-developed carcinomas, occasionally with metastases. Sometimes pericentral hyperplasia was diffuse throughout most or all of one lobe of the liver. These hyperplastic cells collided to become one large nodule and also one large carcinoma. The carcinomas were well-differentiated or moderately well-differentiated and grew on transplantation to isologous hosts. Histologically, the hyperplastic cells adjacent to central veins were increased in size, frequently with double nuclei. Carcinoma cells varied in size and shape and were huge with large nuclei, prominent nucleoli, and eosinophilic cytoplasm. Similar hepatocellular carcinomas were seen previously with carbon tetrachloride, another organochlorine chemical.

Topics: Aldrin; Animals; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; Dieldrin; Female; Hepatic Veins; Hyperplasia; Liver Diseases; Liver Neoplasms; Male; Mice; Mice, Inbred C3H

Topics: Adipates; Alanine Transaminase; Alkaline Phosphatase; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Creatine Kinase; Creatinine; DDT; Dichlorodiphenyl Dichloroethylene; Dieldrin; Environmental Exposure; Humans; L-Lactate Dehydrogenase; Liver; Male; Occupational Diseases; Sugar Acids

Topics: Administration, Oral; Animals; Body Weight; Carcinoma, Hepatocellular; Chemical and Drug Induced Liver Injury; DDT; Dieldrin; Female; Hepatomegaly; Liver Neoplasms; Male; Mice; Mortality; Neoplasm Metastasis; p-Dimethylaminoazobenzene; Sarcoma; Sterilization; Time Factors

Topics: Animals; Chemical and Drug Induced Liver Injury; Dieldrin; DNA; Endoplasmic Reticulum; Enzyme Induction; Female; Heme; Histocytochemistry; Hypertrophy; Liver; Microscopy, Electron; Microsomes; Mitochondria, Liver; Mixed Function Oxygenases; Oxidative Phosphorylation; Oxidoreductases; p-Dimethylaminoazobenzene; Proline; Proteins; Rats

Topics: Aldrin; Chemical and Drug Induced Liver Injury; Dieldrin; Dogs; Hepatitis; Hepatitis A; Insecticides; Kidney Diseases; Pathology; Poisoning; Rats; Research; Statistics as Topic; Toxicology