Reversible Hepatitis Associated with Diclofenac

Ouellette, G. S.; Slitzky, Barry; Gates, Joann; Lagarde, Sjoerd M.; West, A. B.

doi:10.1097/00004836-199104000-00018

Cited by 36 publications

(12 citation statements)

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“…liver and kidney injury as well as gastrointestinal bleeding. Although the incidence is low, it will be important to determine the risk of diclofenac treatment in relation to its possible benefit [45]–[47].…”

Section: Discussionmentioning

confidence: 99%

New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells

et al. 2013

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Non-steroidal anti-inflammatory drugs such as diclofenac exhibit potent anticancer effects. Up to now these effects were mainly attributed to its classical role as COX-inhibitor. Here we show novel COX-independent effects of diclofenac. Diclofenac significantly diminished MYC expression and modulated glucose metabolism resulting in impaired melanoma, leukemia, and carcinoma cell line proliferation in vitro and reduced melanoma growth in vivo. In contrast, the non-selective COX inhibitor aspirin and the COX-2 specific inhibitor NS-398 had no effect on MYC expression and glucose metabolism. Diclofenac significantly decreased glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 1 (MCT1) gene expression in line with a decrease in glucose uptake and lactate secretion. A significant intracellular accumulation of lactate by diclofenac preceded the observed effect on gene expression, suggesting a direct inhibitory effect of diclofenac on lactate efflux. While intracellular lactate accumulation impairs cellular proliferation and gene expression, it does not inhibit MYC expression as evidenced by the lack of MYC regulation by the MCT inhibitor α-cyano-4-hydroxycinnamic acid. Finally, in a cell line with a tetracycline-regulated c-MYC gene, diclofenac decreased proliferation both in the presence and absence of c-MYC. Thus, diclofenac targets tumor cell proliferation via two mechanisms, that is inhibition of MYC and lactate transport. Based on these results, diclofenac holds potential as a clinically applicable MYC and glycolysis inhibitor supporting established tumor therapies.

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Section: Discussionmentioning

confidence: 99%

New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells

et al. 2013

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“…Diclofenac has been reported to be a hepatotoxic compound (Bhogaraju et al 1999; Breen et al 1986; Helfgott et al 1990; Iveson et al 1990; Ouellette et al 1991; Purcell et al 1991; Ramakrishna and Viswanath 1994; Scully et al 1993). From an evaluation of 180 cases of diclofenac hepatotoxicity, Banks et al (1995) reported that the hepatotoxicity was usually asymptomatic, with a few mild symptoms.…”

Section: Discussionmentioning

confidence: 99%

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

Cheong

Kim

Choi

et al. 2007

Environ Health Perspect

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ContextIndustrial waste (which is composed of various toxic chemicals), changes to the disposal process, and addition of chemicals should all be monitored and controlled carefully in the industrial waste industry to reduce the health hazard to workers.Case presentationFive workers in an industrial waste plant developed acute toxic hepatitis, one of whom died after 3 months due to fulminant hepatitis. In the plant, we detected several chemicals with hepatotoxic potential, including pyridine, dimethylformamide, dimethylacetamide, and methylenedianiline. The workers had been working in the high-vapor-generating area of the plant, and the findings of pathologic examination showed typical features of acute toxic hepatitis.DiscussionInfectious hepatitis and drug-induced hepatitis were excluded by laboratory findings, as well as the clinical course of hepatitis. All cases of toxic hepatitis in this plant developed after the change of the disposal process to thermochemical reaction–type treatment using unslaked lime reacted with industrial wastes. During this chemical reaction, vapor containing several toxic materials was generated. Although we could not confirm the definitive causative chemical, we suspect that these cases of hepatitis were caused by one of the hepatotoxic agents or by a synergistic interaction among several of them.Relevance to clinical or professional practiceIn the industrial waste treatment process, the danger of developing toxic hepatitis should be kept in mind, because any subtle change of the treatment process can generate various toxic materials and threaten the workers’ health. A mixture of hepatotoxic chemicals can induce clinical manifestations that are quite different from those predicted by the toxic property of a single agent.

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“…This drug has an inhibitory effect on prostaglandin synthesis and is used as an initial therapy for inflammatory and degenerative rheumatic diseases as well as for pain conditions such as musculoskeletal and post-operative pains and acute attacks of gout and ureteric colic (Morgan, 1999;Perttunun et al, 1999). Diclofenac sodium causes a rare but potentially fetal hepatotoxicity that may be associated with the formation of reactive metabolites and subsequent adverse hepatitis effects may arise in certain individuals (Ouellette et al, 1991, Bhogaraju et al, 1999. NSAIDs are characterized by the ability to inhibit cyclo-oxygenase enzymes, which are involved in the formation of prostaglandins.…”

Section: Introductionmentioning

confidence: 99%

Effect of Diclofenac Sodium in Broilers

Akhter

Sarker

2015

Bangl. J. Vet. Med.

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This study was conducted to determine the effects of diclofenac sodium in broiler chicks during the period from 20 th July /2012 to 1 st september/2012. The broiler chicks were divided into four groups A, B, C and control with ten day old bird in each. Group A was treated with @ 5mg/kg body weight, group B was treated with @ 10mg/kg body weight and Group C was treated with 20 mg/kg body weight given orally mixing with drinking water. Histopathological, hematological and biochemical tests were performed on 42 th days of age to evaluate diclofenac-induced changes between control and treated groups. Mortality rate and pathomorphological changes were observed in dead birds. The acute toxicity was assessed by observing the clinical signs and symptoms, mortality, alterations in blood biochemistry, and necropsy findings. The birds of Group A showed only mild symptoms of diarrhea and 30% mortality. In Group B, 60% and Group 70% of birds died in between 24 and 36 h post-treatment showing the symptoms of segregatory behavior, lethargy, terminal anorexia, and severe bloody diarrhea. Observation of hematological parameters like TEC, Hb, PCV and ESR on 42 th days of age showed significant (p<0.01) decrease in treatment group compare to control group. Observation of biochemical parameters (serum urea, serum creatinine) on 42 th days of age showed significantly increased (p<0.01) serum urea and serum creatinine indicating nephrotoxicity in broilers. At 12 and 24 h post-treatment this returned to the normal levels. The dead birds of the high-dose group also showed similar pattern of biochemical changes at 12 and 24 h post-treatment and revealed extensive visceral gout with characteristic histopathological lesions in liver, kidney, heart, spleen and intestine on post-mortem. The results indicate that diclofenac sodium has hepatotoxic, nephrotoxic, and visceral gout inducing potentials in broilers (cob-500), especially at higher dose.

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Reversible Hepatitis Associated with Diclofenac

Cited by 36 publications

References 0 publications

New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells

New Aspects of an Old Drug – Diclofenac Targets MYC and Glucose Metabolism in Tumor Cells

Grand Rounds: An Outbreak of Toxic Hepatitis among Industrial Waste Disposal Workers

Effect of Diclofenac Sodium in Broilers

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