https://www.annemergmed.com/article/S0196-0644(89)80933-3/pdf

Drug- and toxin-induced rhabdomyolysis

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Toxicological profile for alpha-, beta-, gamma, and delta-hexachlorocyclohexane

To develop novel markers for hepatocellular carcinomas (HCC), 10 cases were analyzed by 2-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry. Results were compared to those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE revealed that 3 variants of class 3 aldehyde dehydrogenase (ALDH-3) newly appeared while 2 variants of ALDH-2 diminished to undetectable levels in HCC. However, 4 ALDH-1 variants with different pIs remained unaffected. This pattern of concomitant appearance and disappearance of ALDH-3 and ALDH-2 variants was consistently observed in all HCC tissues. Our results suggest that alterations of ALDH isozyme variants may be closely correlated to HCC and that proteomic analysis of these proteins might be a novel approach to identify the molecular events in detail during hepatocarcinogenesis. © 2002 Wiley-Liss, Inc.

Proteomic alterations of the variants of human aldehyde dehydrogenase isozymes correlate with hepatocellular carcinoma

The focus on the refinement, reduction and replacement of animal use in toxicity testing requires the development of cell-based systems that mimic the effects of xenobiotics in human tissues. The human adrenocortical carcinoma cell line, H295R, has been proposed as a model for studies on adrenal steroidogenesis and its disruption. In this study, expression profiles for nine adrenal steroidogenic genes were characterized in H295R cells using real-time RT-PCR. Treatment with forskolin increased cortisol secretion and stimulated transcription of all the steroidogenic genes except SULT2A1. The transcript profile from H295R cells in the presence and absence of forskolin was compared with the transcript profile from human adrenal glands. The gene expression pattern observed in the forskolin-treated H295R cells was more similar to that in the human adrenal gland, than the expression pattern in untreated cells. To examine H295R cells as a possible in vitro system for the assessment of adrenal disruption using molecular endpoints, the insecticide lindane (gamma-hexachlorocyclohexane) was used. In vivo, lindane has been shown to inhibit testicular, ovarian and adrenal steroidogenesis. It was demonstrated that lindane reduced cortisol secretion, downregulated the expression of a subset of the genes encoding steroidogenic enzymes and repressed transcriptional activation of the steroidogenic acute regulatory protein (StAR) gene promoter. Thus the H295R cell line provides a good in vitro system for the analysis of the human adrenal steroidogenic pathway at the level of hormone production and gene expression. This in vitro test can be used for the rapid detection of adrenal endocrine disruption and as a tool for mechanistic studies.

Steroidogenic gene expression in H295R cells and the human adrenal gland: adrenotoxic effects of lindane in vitro.

Drug- and Toxin-Induced Seizures

Six cases of oral intoxication with lindane-solvent mixtures are reviewed. The ingested doses of lindane (mean dosage 120 mg/kg +/- 86 mg/kg) and benzene (mean dosage 366 mg/kg +/- 93 mg/kg) exceeded the toxic level. Symptoms (vomiting, dizziness and hyperreflexia) occurred within 30 min and all patients had epileptiform seizures. Two patients suffered from pulmonary edema and one of them had a severe rhabdomyolysis. Diazepam was sufficient to control convulsions in five cases. Gastric lavage was performed in five patients and activated charcoal, liquid paraffin with saline cathartic, and cholestyramine were used as adsorbents. Recovery was complete in all patients.

A Haubenstock

Papers

Acute oral poisoning with lindane-solvent mixtures.