Benoxaprofen induced toxicity in isolated rat hepatocytes.

  title={Benoxaprofen induced toxicity in isolated rat hepatocytes.},
  author={Kathleen M. Knights and Michael R. Cassidy and Roger M. Drew},
  volume={40 3},
The toxicity of benoxaprofen, a non-steroidal anti-inflammatory compound was investigated using rat hepatic microsomal and isolated hepatocyte suspensions. In microsomes, benoxaprofen produced a Type I binding spectra and competitively inhibited (ki 380 microM) the oxidative metabolism of aminopyrine. Marked toxicity was observed following incubation of benoxaprofen with isolated hepatocytes from either untreated, phenobarbitone (PB) or 3-methylcholanthrene (3-MC) pretreated male rats. In… Expand
The effects of ibuprofen enantiomers on hepatocyte intermediary metabolism and mitochondrial respiration.
R-ibuprofen should be considered more in terms of metabolism to a reactive acyl-CoA intermediate rather than as a pro-drug for the pharmacologically active S-enantiomer, according to the results of this study. Expand
Induction of the cytochrome P450 I and IV families and peroxisomal proliferation in the liver of rats treated with benoxaprofen. Possible implications in its hepatotoxicity.
It is concluded that benoxaprofen is a peroxisomal proliferator which selectively induces the hepatic cytochrome P450 I and IV families. Expand
Idiosyncratic liver toxicity of nonsteroidal antiinflammatory drugs: molecular mechanisms and pathology.
This review explores the clinical hepatic pathology associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs), possible cellular and molecular mechanisms of injury, and futureExpand
Role of Metabolism in Drug-Induced Idiosyncratic Hepatotoxicity
Evidence for metabolic activation of a drug to a reactive intermediate is a necessary, yet insufficient, step in the generation of an idiosyncratic reaction is reviewed and the potential role that high dosages may play in these adverse reactions is considered. Expand
Nonsteroidal antiinflammatory drugs and leukotriene receptor antagonists
This chapter presents an update on the clinical presentation and pathological spectrum of hepatotoxicity with these classes of agents, including reports of patients who progressed to acute liver failure. Expand
Side-effects of non-steroidal anti-inflammatory drugs.
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  • Medicine
  • Bailliere's clinical rheumatology
  • 1988
Despite a continuing lack of good quality epidemiological studies, our knowledge of the side-effects of NSAIDs has advanced in recent years. The most important reactions are those which are relatedExpand
Exploration of the Biological Potential of Benzoxazoles: An Overview
The development of benzoxazole containing drugs and research compounds has been discussed in the present review along with its varied pharmacological activities such as antimicrobial,Expand
In Vitro Screens From Cns, Liver and Kidney for Systemic Toxicity
Progress made in developing toxicity screens for three common target organs is presented, and further work needed for more complete validation is identified. Expand


Paracetamol metabolism and toxicity in isolated hepatocytes from rat and mouse.
  • P. Moldéus
  • Chemistry, Medicine
  • Biochemical pharmacology
  • 1978
Hepatocytes isolated from mouse and rat catalyzed the formation of glucuronide, sulphate, glutathione and cysteine conjugates of paracetamol, which was directly correlated with loss of intracellular glutATHione (GSH) and induced rate was only half of that in hepatocytes from control mouse. Expand
Disposition and metabolism of benoxaprofen in laboratory animals and man.
In man, rhesus monkey and rabbit, excretion in the urine was a major route, whilst biliary--faecal excretion was the only effective route in the rat and dog, and no major metabolic transformation of benoxaprofen was observed. Expand
A highly sensitive radiometric assay for zoxazolamine hydroxylation by liver microsomal cytochrome P-450 and P-448: properties of the membrane-bound and purified reconstituted system.
A radiometric assay for the in vitro metabolism of zoxazolamine has been developed which combines high sensitivity and rapid determination of product and revealed that cytochrome P -448 from 3-methylcholanthrene-treated rats was approximately 10- to 15-fold more efficient than cyto Chrome P -450 from phenobarbital-treated Rats in catalyzing the hydroxylation of z oxazolamines. Expand
Uncoupling of Oxidative Phosphorylation by some Arylacetic Acids (Anti-inflammatory or Hypocholesterolemic Drugs)
Evidence has been obtained that these two drugs also uncouple oxidative phosphorylation in a connective tissue (cartilage) since they selectively inhibit both the incorporation of inorganic phosphate-32P into organic phosphates and the ATP-dependent bio synthesis of mucopolysaccharide sulphates, without significantly affecting the oxidation of glucose-14C and octanoate- 14C, by the cartilage tissue. Expand
A pharmacokinetic interaction in man between phenobarbitone and fenoprofen, a new anti-inflammatory agent.
The plasma elimination rate constants increased significantly and the rats excreted proportionately more metabolized fenoprofen in the urine, consistent with an increase in the rate of metabolism of feniprofen. Expand
Biochemical and pharmacological changes in the rat following chronic administration of morphine nalorphine and normorphine.
The N-demethylating enzyme is proposed as a model for the study of narcotic-drug receptor sites and the degree of tolerance, cross-tolerance and depression of enzymatic activity depends on the amount of drug given per day rather than on the duration of drug administration. Expand
Spectral studies of drug interaction with hepatic microsomal cytochrome.
Two types of spectral changes are described as resulting from substrate interaction with a hepatic microsomal cytochrome; the magnitude of these spectral changes is dependent on protein concentrationExpand
Characterization of three highly purified cytochromes P-450 from hepatic microsomes of adult male rats.
Results of this study indicate that rat hepatic microsomal cytochromes P-450 are composed of at least four hemoproteins with CO-reduced absorbance maxima between 447-448 nm and a minimum of four microsomes are now known to 16 alpha-hydroxylate testosterone. Expand
Benoxaprofen and papillary necrosis.
In the present case the evolution of the clinical findings clearly indicated a relation of this lupus-like syndrome to administration of methyldopa, and the development of a lupuses erythematosus Syndrome must be added to the list of possible side effects of the drug. Expand
Bleb formation in hepatocytes during drug metabolism is caused by disturbances in thiol and calcium ion homeostasis.
Disturbances in intracellular thiol and calcium ion homeostasis therefore seem to be responsible for the surface blebbing observed during toxic injury to isolated hepatocytes. Expand