succimer and Chemical-and-Drug-Induced-Liver-Injury

Topics: Chemical and Drug Induced Liver Injury; Databases, Factual; Drug Labeling; Humans; Pharmaceutical Preparations; Risk

Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

Topics: Acetylcysteine; Animals; Arsenites; Chemical and Drug Induced Liver Injury; Male; Oxidative Stress; Rats; Rats, Wistar; Sodium Compounds; Succimer

Topics: Chelating Agents; Chemical and Drug Induced Liver Injury; Child, Preschool; Constipation; Diagnosis, Differential; Humans; Lead Poisoning; Male; Succimer

Chronic arsenic toxicity due to drinking arsenic-contaminated water has been one of the worst environmental health hazards affecting eight districts of West Bengal since the early eighties. Detailed clinical examination and investigation of 248 such patients revealed protean clinical manifestations of such toxicity. Over and above hyperpigmentation and keratosis, weakness, anaemia, burning sensation of eyes, solid swelling of legs, liver fibrosis, chronic lung disease, gangrene of toes, neuropathy, and skin cancer are some of the other manifestations. A cross-sectional survey involving 7683 participants of all ages was conducted in an arsenic-affected region between April 1995 and March 1996. Out of a population of 7683 surveyed, 3467 and 4216 people consumed water containing As below and above 0.05 mg/L, respectively. Except pain abdomen the prevalence of all other clinical manifestations tested (e.g., pigmentation, keratosis, hepatomegaly, weakness, nausea, lung disease and neuropathy) were found to be significantly higher in As exposed people (water As > 0.05 mg/L) compared to control population (water As level < 0.05 mg/L). The prevalence of pigmentation and keratosis, hepatomegaly, chronic respiratory disease and weakness rose significantly with increasing arsenic concentrations in drinking water. The respiratory effects were most pronounced in individuals with high arsenic water concentrations who also had skin lesion. Therapy with chelating agent DMSA was not found to be superior to placebo effect. However, therapy with DMPS caused significant improvement of clinical condition of chronic arsenicosis patients as evidenced by significant reduction of total clinical scores from 8.90 +/- 2.84 to 3.27 +/- 1.73; p < 0.0001. Efficacy of specific chelation therapy for patients suffering from chronic As toxicity has further need to be fully substantiated. However, supportive treatment could help in reducing many symptoms of the patients. Treatment in hospital with good nutritious diet has been found to reduce symptom score in a subset of placebo treated patients in West Bengal during the course of DMSA and DMPS trial. People should be advised to stop drinking As contaminated water or exposure to As from any other source. The various clinical manifestations should be treated symptomatically.

Topics: Abdominal Pain; Adult; Arsenic Poisoning; Chelating Agents; Chemical and Drug Induced Liver Injury; Cross-Sectional Studies; Female; Humans; India; Male; Middle Aged; Nausea; Nervous System Diseases; Nutritional Support; Pulmonary Fibrosis; Skin Diseases; Succimer; Water Supply

The effect of meso 2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) on gallium arsenide (GaAs) induced liver damage was studied. The oral feeding rat model was used in this study. The animals were exposed to 10 mg/kg GaAs, orally, once daily, 5 days a week for 24 weeks and treated thereafter with single oral daily dose of either 0.3 mmol/kg DMSA or MiADMSA for two course of 5 days treatment. The animals were sacrificed thereafter. Lipid peroxidation was assessed by measuring liver thiobarbituric acid reactive substance (TBARS). Liver damage was assessed by number of biochemical variables and by light microscopy. The activity of superoxide dismutase (SOD) and delta-aminolevulinic acid dehydratase (ALAD) beside reduced glutathione (GSH) concentration was measured in blood. Exposure to GaAs produced a significant reduction in GSH while, increased the oxidized glutathione (GSSG) concentration. Hepatic glutathione peroxidase (GPx) and catalase activity increased significantly while level of serum transaminase increased moderately. Gallium arsenide exposure also produced marked hepatic histopathological lesions. Overall, treatment with MiADMSA proved to be better than DMSA in the mobilization of arsenic and in the turnover of some of the above mentioned GaAs sensitive biochemical alterations. Histopathological lesions also, responded more favorably to chelation treatment with MiADMSA than DMSA.

Topics: Alanine Transaminase; Animals; Arsenicals; Aspartate Aminotransferases; Catalase; Chelating Agents; Chemical and Drug Induced Liver Injury; Gallium; Glutathione; Glutathione Peroxidase; Lipid Peroxidation; Liver Function Tests; Male; Metals; Oxidation-Reduction; Oxidative Stress; Porphobilinogen Synthase; Rats; Succimer; Superoxide Dismutase

Topics: Acetaminophen; Chemical and Drug Induced Liver Injury; Child; Drug Synergism; Female; Humans; Mercury; Mercury Poisoning; Succimer

The efficacy of three chelating agents, BAL, DMPS and DMSA has been evaluated in rabbits as treatments for systemic dichloro(2-chlorovinyl)arsine [lewisite] poisoning by the percutaneous route. Chelating agent treatment reduced the incidence and severity of pathological liver changes following lewisite poisoning. There was no marked difference between the three chelating agents for protection against lethality when screened at an equimolar dose of 40 mumol kg-1. The results indicated DMPS and DMSA may prolong survival time compared with BAL. The low toxicity of DMPS and DMSA compared to BAL enabled doses of 160 mumol kg-1 on a more prolonged dosing schedule to be used for DMPS and DMSA. This schedule showed DMPS and DMSA to give a significant improvement in protection against the lethal effects of percutaneous lewisite compared to that of BAL. It was concluded that DMPS and DMSA have significant advantages over BAL for use as treatment for systemic lewisite poisoning.

Topics: Administration, Topical; Animals; Arsenic Poisoning; Arsenicals; Chelating Agents; Chemical and Drug Induced Liver Injury; Dimercaprol; Gallbladder; Lethal Dose 50; Liver; Lung; Male; Rabbits; Succimer; Sulfhydryl Compounds; Unithiol