Acute hepatitis; toxic or viral?
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Hepatitis↗
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Results for “HEPATITIS, TOXIC”
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Effect of curcumin and eugenol on iron-induced hepatic toxicity in rats.
Male Wistar rats injected i.p. with 30 mg Fe2+/kg body weight show hepatic damage as measured by an increase in lipid peroxides which correlated with elevated serum enzymes, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and lactate dehydrogenase (LDH). Oral administration of spice principles, curcumin from turmeric (30 mg/kg body weight) or eugenol from cloves (100 mg/kg body weight), for 10 days lowered the liver and serum lipid peroxide levels, serum ALAT, ASAT and LDH, enhanced by i.p. injection of iron. This study indicates that curcumin or eugenol reduces the iron-induced hepatic damage by lowering lipid peroxidation.
Alanine Transaminase↗
[Ecstasy-induced toxic hepatitis].
INTRODUCTION: The use of ecstasy (MDMA) has developed in the young since the eighties, particularly in festive settings. Among the severe adverse events induced by this synthetic drug, the hepatotoxicity related to MDMA and to its physiopathological mechanism warrant attention. OBSERVATION: A 21 year-old man consulted for anaemia that had persisted over the past months with abnormality in hepatic profile. The imputability of ecstasy in perturbations in his hepatic profile was highly probable in view of the fact that his transaminase level returned to normal one month after he stopped taking the drug, all the viral markers of hepatitis became negative and in the absence of concomitant consumption of any psycho-active drugs other than cannabis. DISCUSSION: A review of the literature showed the great variability in clinical pictures related to the hepato-toxicity of ecstasy, ranging from acute to lethal, fulminating hepatitis. The physiopathological mechanism of this phenomenon is little known. Various hypotheses are evoked with, among others, immuno-allergic-type hypersensitivity, phenomenon of apoptosis, vitamin E deficiency, and the role of occasionally concomitant malignant hyperthermia. The part played by the metabolites of the synthetic drug has also been suggested as well as individual variations in genetic origin with regards to the risk of developing acute hepatitis after ingestion of ecstasy. The hepato-toxicity of this drug does not appear to be dose-dependant nor related to the cumulated duration of exposure.
Adult↗
[Renal and hepatic toxicity studies in mice treated with sodium saccharin: breaks in single-stranded DNA].
The renal and hepatic effects of in vivo treatment with saccharin have been determined as increased DNA elutability on filter. A direct dose-damage relationship was not observed in the kidney and in the liver DNA of treated mice. Doses of 50, 100 and 200 mg/Kg seem to induce in almost all the experiments the same level of single-stranded breaks. The DNA elutability is increased in the range 130-210 % if compared with controls.
Animals↗
Renal and hepatic toxicity of trichloroethylene and its glutathione-derived metabolites in rats and mice: sex-, species-, and tissue-dependent differences.
Acute cytotoxicity (lactate dehydrogenase release) of trichloroethylene (TRI), S-(1,2-dichlorovinyl)glutathione (DCVG), and S-(1,2-dichlorovinyl)-L-cysteine (DCVC) in freshly isolated renal cortical cells and hepatocytes from male and female rats was evaluated to test the hypothesis that the assay provides a valid indicator of sex- and tissue-dependent differences in sensitivity to TRI and its metabolites. We then determined mitochondrial toxicity (inhibition of state-3 and/or stimulation of state-4 respiration) in renal cortical and hepatic mitochondria from male and female rats and mice to assess sex-, tissue-, and species-dependent susceptibility. TRI was moderately cytotoxic in renal cells from male rats but was nontoxic in renal cells from female rats or hepatocytes from male or female rats. Acute cytotoxicity of both DCVG and DCVC was greater in renal cells from male rats than in renal cells from female rats. Although DCVC does not target the liver in vivo, it was a very potent hepatotoxicant in vitro. Mitochondrial toxicity in kidney and liver showed similar patterns, with mitochondria from male rats being more sensitive than mitochondria from female rats; order of potency was DCVC > DCVG >> TRI. State-3 respiration in mitochondria from mice was also inhibited, but the patterns and relative sensitivities differed from those in mitochondria from rats. Renal and hepatic mitochondria from mice were less sensitive than corresponding mitochondria from rats and renal mitochondria from female mice were significantly more sensitive than renal mitochondria from male mice. Thus, many of the species-, sex-, and tissue-dependent differences in toxicity observed in vivo are also observed in vitro.
Animals↗
Acute renal and hepatic toxicity of 2-haloanilines in Fischer 344 rats.
Aniline and its halogenated derivatives are widely used as chemical intermediates. The purpose of this study was to determine the hepatotoxic and nephrotoxic potential of the 2-haloanilines. Male Fischer 344 rats (n > or = 4) were injected (i.p.) with 1.0 or 1.25 mmol/kg of: aniline (A), 2-fluoroaniline (2-FA), 2-chloroaniline (2-ClA), 2-bromoaniline (2-BrA), 2-iodoaniline (2-IA) or vehicle (0.9% saline, 2.5 ml/kg). All compounds were injected as hydrochloride salts. Renal and hepatic function was monitored 24 h after treatment. All of the 2-haloanilines induced oliguria, diminished kidney weight, tubular casts and decreased renal cortical slice accumulation of organic anions. Blood urea nitrogen (BUN) levels were increased (P < 0.05) by treatment with 1.0 or 1.25 mmol/kg of 2-FA, 2-ClA or 2-BrA. Hepatic alterations were also observed and characterized by elevated plasma ALT/GPT activity and altered morphology in the centrilobular region. The nephrotoxic and hepatotoxic potentials were similar among the 2-haloanilines but aniline was less toxic than its 2-halo derivatives. These results demonstrated that halogen substitution at the 2-position of aniline increased hepatic and renal toxicity. However, the severity of toxicity was not influenced by the nature of the halogen substituent.
Acute Disease↗
Subclinical hepatic toxicity during combination chemotherapy for breast cancer.
We evaluated serial liver function tests (LFT) and serial liver imaging procedures for 190 consecutive patients with breast carcinoma to assess the incidence and severity of hepatic abnormalities during treatment with combination chemotherapy. Thirty-four percent of patients receiving adjuvant chemotherapy and 52% of patients being treated for metastatic breast cancer had one or more LFT abnormalities before initiation of therapy. Among patients with normal baseline LFT results, 77% of those receiving adjuvant chemotherapy and 82% being treated for metastatic breast cancer developed LFT abnormalities during therapy. Liver function test abnormalities were mild to moderate and never led to interruption of treatment; they appeared within the first three months of chemotherapy and normalized in 90% within one year of cessation of treatment. Our analysis suggests that LFT abnormalities detected during the administration of chemotherapy for patients with breast cancer are a manifestation of drug toxicity and that such abnormalities are insufficient evidence of hepatic metastases.
Alkaline Phosphatase↗
Liver pathology following hepatic arterial infusion chemotherapy. Hepatic toxicity with FUDR.
The authors reviewed the liver histopathology and the clinical features of eight patients with liver metastases from colorectal cancer who were treated by hepatic arterial infusion chemotherapy (HAIC) via an implantable pump (Infusaid). Before HAIC, these patients had no evidence of hepatitis, and results of liver biopsies performed on three patients showed only minor morphologic alterations. All the liver tumors responded to HAIC, but all patients developed hepatitis. Clinical findings included nausea, vomiting, abdominal pain and jaundice. Serum transaminases, alkaline phosphatase and bilirubin levels were increased. Clinical observations suggested that 5-fluoro-2'-deoxyuridine (FUDR), the predominant drug given, was the hepatotoxic agent. Toxic effects were hepatocyte necrosis, steatosis, cholestasis, central vein sclerosis, and alterations in the portal triad. In addition, central vein lesions like those in veno-occlusive disease, and micronodular cirrhosis resembling that induced by alcohol, were encountered. Although individual susceptibility to FUDR appeared to vary, portal triad fibrosis was present in all eight cases and, together with central vein sclerosis and cirrhosis, appeared to be related to the dose and duration of HAIC.
Adult↗
Cultured hepatocytes as investigational models for hepatic toxicity: practical applications in drug discovery and development.
Drugs can fail at any phase during discovery, preclinical or clinical development due to unacceptable levels of toxicity, and liver is commonly the principle target organ. Investigational toxicology methods, using appropriate models and hypotheses, can often resolve problems, identify toxic chemical substituents and salvage therapeutic discovery programs. While in vivo models are used to investigate hepatic drug effects in the context of toxicokinetics and systemic influences, cell culture models provide in vitro systems for investigating specific mechanisms in a precisely controlled environment. Using primary hepatocytes isolated from laboratory animals, we have explored several drug-induced hepatic disorders that surfaced during different phases of drug discovery and development. Additionally, the use of human hepatocytes has allowed us to address concerns for human exposure, examine human relevance of animal data, and provide perspective on problems encountered in clinical trials.
Animals↗
Assessment of hepatic toxicity from treatment with 90Y-SMT 487 (OctreoTher(TM)) in patients with diffuse somatostatin receptor positive liver metastases.
The purpose of this study was to determine whether there is evidence for hepatocellular radiation injury following treatment with (90)Y-SMT487 ((90)Y-DOTA-tyr3-octreotide, OctreoTher(TM)) in patients with extensive liver metastases from neuroendocrine tumors. Patients reported in this study participated in a Phase II trial of efficacy and safety of (90)Y-SMT487. The trial design called for three treatment cycles of 120 mCi each (4400 MBq) of (90)Y-SMT487. (111)In-pentetreotide SPECT images were used to determine the extent of liver metastases. Serum AST, ALT, and alkaline phosphatase levels were obtained at baseline and following each cycle of therapy. Least squares fit was applied to the serial liver enzyme measurements in patients with extensive liver metastases. Post-therapy liver enzyme measurements were also evaluated using WHO common toxicity criteria. Repeated-measures ANOVA and paired t-test were applied to the serial enzyme measures. There were 21 subjects. Fifteen of these had hepatic metastases with 12 demonstrating extensive (defined as 25% or more) liver involvement. In only 4 of these 15 did any of the three enzyme levels increase in WHO toxicity grade from baseline to final follow-up. We conclude that patients with diffuse SSTR positive hepatic metastases can be treated with a cumulative administered activity of 360 mCi (90)Y-SMT487 with only a small chance of developing mild acute or subacute hepatic radiation injury.
Alanine Transaminase↗
[The problem of hepatic toxicity of oral antidiabetics; clinical experiences & experimental animal studies].
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Animals↗
Role of tumor necrosis factor-alpha in the development of spontaneous hepatic toxicity in Long-Evans Cinnamon rats.
The objective of this study was to evaluate the potential role of TNF-alpha in the onset of acute hepatitis in the Long-Evans Cinnamon (LEC) rat, an animal model for inherited copper (Cu) toxicosis. In LEC rats, Cu is accumulated in the liver with age, and clinical signs of acute hepatitis were observed as, icterus, reduced body weight, nasal bleeding, dehydration, and reduced food intake at 12 weeks of age. Cellular changes such as apoptosis in the liver were evident in these rats with increasing age. Positive TNF-alpha and TNFR1 immunostainings were observed in hepatocytes and Kupffer cells in LEC rats. Hepatic levels of caspase-3 activity, TNF-alpha mRNA, and protein were also increased in LEC rats from 6 to 12 weeks of age as compared with control Long-Evans (LE) rats. The neutralization of TNF-alpha by passive immunization or the inhibition of caspase activity can block the apoptotic process initiated by TNF-alpha. In this study, we evaluated the effects of passive immunization of LEC rats with weekly administration of anti-rat TNF-alpha on Cu-induced acute hepatitis. This treatment resulted in a reduction of the percentage of apoptotic cells in the liver, decreased activity of caspase-3, and also in down-regulation of the TNF-alpha gene expression. Thus, these results suggest a major role for TNF-alpha on the pathogenesis of Cu-induced acute hepatitis in LEC rats.
Alanine Transaminase↗
Epidemic of toxic hepatitis in India of possible mycotoxic origin.
An epidemic of liver disease, characterized by onset with high fever, rapidly progressive jaundice, and ascites occurred in a rural area of India. Several hundred people were affected and mortality was high. The epidemic was heralded by the appearance of similar features in the village dogs. Liver biopsy specimens from eight cases and autopsy material from one human case and two dogs were studied. Characteristic features were centrizonal scarring, hepatic venous occlusion, ductular proliferation and cholestasis, focal syncytial giant-cell tr-nsformation of hepatocytes, and pericellular fibrosis. Toxic quantities of aflatoxin B1 were found in samples of corn, the staple food grain of the people, that was obtained from the domestic food stores. The etiology of the disease could not be unequivocally established, but aflatoxins, perhaps in combination with other factors, may have been the cause.
Aflatoxins↗
The hepatic toxicity of amithiozone.
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Anti-Bacterial Agents↗
Hypersensitivity to salicylazosulfapyridine: renal and hepatic toxic reactions.
Salicylazosulfapyridine has been used for a number of years as therapy for ulcerative colitis. Reported toxicities are usually minor. This case report represents an acute allergic reaction to the drug. Characterized by fever, rash, eosinophilia, nephritis, and hepatitis. Resolution occurred with discontinuation of salicylazosulfapyridine. Although similar reactions have been reported with the antimicrobial sulfonamides, none has been fully described with salicylazosulfapyridine, a combination of a sulfonamide and salicylate.
Adult↗
Improvement of anaemia in haemodialysed patients after viral or toxic hepatic cytolysis.
Thirty patients receiving haemodialysis, including two who had undergone bilateral nephrectomy, showed significant increases (p less than 0.001) in packed cell volume, haemoglobin concentration, and reticulocyte count during an episode of viral or toxic liver cytolysis. In 19 cases the episode lasted a mean of 5.0 +/- SD 2.9 months and was accompanied by improved haematological values for a mean of 12.0 +/- 6.0 weeks. Of the remaining patients, in whom the episode lasted a mean of 8.0 +/- 3.5 months (p less than 0.02), seven showed continued improvement a mean of 30.0 +/- 16.0 weeks after cytolysis. In eight patients in this group there was an apparent correlation between persistently increased haemoglobin concentrations and biopsy evidence of chronic hepatitis. The findings suggest that the reduction in anaemia resulted from enhanced red-cell production mediated by secretion of erythropoietin from regenerating liver cells. If confirmed this might have important implications for the treatment of anaemia in chronic renal insufficiency.
Adolescent↗
BETA-PROPIOLACTONE PLUS ULTRAVIOLET IRRADIATED PLASMA. A CLINICAL EVALUATION FOR HEPATITIS, TOXICITY AND ALLERGY.
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Anti-Infective Agents, Local↗
French pharmacovigilance survey evaluating the hepatic toxicity of coumarin.
Synthetic coumarin (benzopyrone) was launched in France in 1988 for the adjuvant therapy of lymphoedema of the upper limb following radiosurgical treatment of breast cancer. Further to the reporting of hepatic reactions, a national survey has been carried out. The survey dealt with 22 cases reported to the pharmacovigilance regional centres and 20 to Knoll France company (five duplicate cases) up to June 1996. Thirty-four cases corresponding to an elevation of ALT over 2N and/or alkaline phosphatase over 1.5N (criteria chosen for selection in this survey) had been taken into account. Among these cases, a causal relationship was considered likely or probable for 15 of them. Two positive rechallenges were reported. The hepatic reactions observed between 2 to 6 months of treatment in two-thirds of the cases (average dose: 90 mg/day; i.e. recommended dose) was essentially cytolytic in 85% of the cases, with jaundice in 14 cases and hyperbilirubinaemia reported in five other cases. In 23 cases (68%), the increase of ALT exceeded 10N. Of the patients 41% were hospitalized. Severe liver failure with encephalopathy justified liver transplantation once and likely led to encephalopathy and fatal evolution in two other cases. The evolution was favourable in the other cases. The drug was prescribed for other uses than the registered indication in more than 50% of these cases. No risk factors could be identified in the survey. This survey provides a strong signal for potential hepatotoxicity of coumarin (likely due to the production of a reactive metabolite in some patients exhibiting a coumarin 7-hydroxylation deficiency).
Journal Article↗