Nimesulide-Induced Acute Hepatitis

Sbeit, Wisam; Krivoy, Norberto; Shiller, Moshe; Farah, Raymond; Cohen, Hector; Struminger, Lili; Reshef, Ron

doi:10.1177/106002800103500901

Cited by 25 publications

(13 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Nimesulide has been associated with adverse reactions in the liver, including increases in serum aminotransferase activities, hepatocellular necrosis, and/or intrahepatic cholestasis (Boelsterli, 2002). Many cases of nimesulide induced hepatotoxicity and renal failure have been reported in humans (Apostolou et al, 1997;Sbeit et al, 2001). A wide range of liver injuries ranging from asymptomatic elevated liver function enzymes (Pasquale et al, 1993) to fatal acute hepatic and renal failure (Schattner et al, 2000) have been reported.…”

Section: Discussionmentioning

confidence: 99%

Nimesulide-induced acute biliary tract injury and renal failure in a kitten: a case report

Börkü¹,

Güzel²,

Karakurum³

et al. 2008

Vet. Med. - Czech

View full text Add to dashboard Cite

ABSTRACT:A 3-month-old male kitten was presented to our clinic with malaise, vomiting and jaundice. In the anamnesis, we learned that the cat had a history of anorexia, sneezing, and nasal discharge and that the owner had administered 100 mg/day (t.i.d.) nimesulide orally for three days. In the laboratory study, high levels of serum alkaline phosphatase, γ-glutamyl transtransferase, total bilirubin, direct bilirubin, indirect bilirubin, urea, and creatinine were detected. All the clinical signs and laboratory abnormalities returned to normal levels after cessation of the nimesulide and supportive treatment. In this case, clinical and laboratory findings were thought to be compatible with nimesulide-induced acute biliary injury and renal failure. This case report indicates that the household pets are at risk of toxic drugs administered by their owners and great caution should be taken in administering NSAIDs in cats.

show abstract

Section: Discussionmentioning

confidence: 99%

Nimesulide-induced acute biliary tract injury and renal failure in a kitten: a case report

Börkü¹,

Güzel²,

Karakurum³

et al. 2008

Vet. Med. - Czech

View full text Add to dashboard Cite

show abstract

“…1 for structure). The drug can cause several types of liver damage, ranging from mild abnormal function to severe organ injuries; these effects are usually reversible upon discontinuation of the drug but occasionally can progress to fatal hepatic failure (Ferreiro et al, 2000;Schattner et al, 2000;Merlani et al, 2001, Montesinos et al, 2001Sbeit et al, 2001). We previously demonstrated that nimesulide is a powerful protonophoretic uncoupler and NAD(P)H oxidant in isolated rat liver mitochondria, inducing Ca 2ϩ efflux, or mitochondrial permeability transition (MPT) in the presence of ruthenium red, whereas its reduced metabolite lacks these effects (Mingatto et al, 2000).…”

mentioning

confidence: 99%

The Critical Role of Mitochondrial Energetic Impairment in the Toxicity of Nimesulide to Hepatocytes

Mingatto

Rodrigues²,

Pigoso³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

View full text Add to dashboard Cite

We described the effects of nimesulide (N-[4-nitro-2-phenoxyphenyl]-methanesulfonamide) and its reduced metabolite in isolated rat hepatocytes. Nimesulide stimulated the succinatesupported state 4 respiration of mitochondria, indicating an uncoupling effect of the drug. Incubation of hepatocytes with nimesulide (0.1-1 mM) elicited a concentration-and time-dependent decrease in cell viability as assessed by lactate dehydrogenase leakage, a decrease of mitochondrial membrane potential as assessed by rhodamine 123 retention, and cell ATP depression. Nimesulide also decreased the levels of NAD(P)H and glutathione in hepatocytes, but the extent of the effects was less pronounced in relation to the energetic parameters; in addition, these effects did not imply the peroxidation of membrane lipids. The decrease in the viability of hepatocytes was prevented by fructose and, to a larger extent, by fructose plus oligomycin; it was stimulated by proadifen, a cytochrome P450 inhibitor. In contrast, the reduced metabolite of nimesulide did not present any of the effects observed for the parent drug. These results indicate that: 1) nimesulide causes injury to the isolated rat liver cells, 2) this effect is mainly mediated by impairment of ATP production by mitochondria due to uncoupling, and 3) on account of the activity of its nitro group, the parent drug by itself is the main factor responsible for its toxicity to the hepatocytes.

show abstract

“…Under the Heck reaction conditions compound 3 was coupled with a variety of alkenes in the presence of Pd(OAc) 2 and i Pr 2 NEt at 75-80…”

Section: Resultsmentioning

confidence: 99%

“…Indeed because of the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries and restricted by the European Medicines Agency. The use of this drug has been reported to cause several types of liver damage, [2] ranging from mild abnormal function to severe organ injuries. These effects are usually reversible upon discontinuation of the drug but occasionally can progress to fatal hepatic failure.…”

Section: Introductionmentioning

confidence: 99%

Palladium‐mediated synthesis of novel nimesulide derivatives

Durgadas¹,

Chatare²,

Mukkanti³

et al. 2010

Applied Organom Chemis

View full text Add to dashboard Cite

Synthesis of a series of compounds structurally related to the anti-inflammatory agent nimesulide has been accomplished via Pd-catalyzed C-C bond forming reactions. Thus 4-iodo derivative, prepared from nimesulide, participated in Sonogashira (copper-free), Heck and Suzuki coupling reactions to afford the corresponding alkynyl, alkenyl and aryl substituted products. Some of the compounds synthesized were tested for anti-inflammatory activities in vivo.

show abstract

Nimesulide-Induced Acute Hepatitis

Cited by 25 publications

References 12 publications

Nimesulide-induced acute biliary tract injury and renal failure in a kitten: a case report

Nimesulide-induced acute biliary tract injury and renal failure in a kitten: a case report

The Critical Role of Mitochondrial Energetic Impairment in the Toxicity of Nimesulide to Hepatocytes

Palladium‐mediated synthesis of novel nimesulide derivatives

Contact Info

Product

Resources

About