Idiosyncratic NSAID drug induced oxidative stress

Galati, Giuseppe; Tafazoli, Shahrzad; Sabzevari, Omid; Chan, Tom S.; O’Brien, Peter J.

doi:10.1016/s0009-2797(02)00052-2

Cited by 128 publications

(86 citation statements)

References 44 publications

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“…Similar dose of DIC has been shown to induce massive DNA fragmentations, increase the MDA level and to deplete the levels of GSH and SOD in rat liver [5]. The mechanism of DIC-induced ROS generation has been shown to involve peroxidase-catalyzed production of DIC radicals [9] and cytochrome P450-mediated bioactivation of DIC [4]. DIC, however, found to induced liver damage through various mechanisms such as covalent protein modification by reactive metabolites [6; 7; 8] and mitochondrial injury [10; 11].…”

Section: Discussionmentioning

confidence: 97%

Curcuma longa, Glycyrrhiza glabra and Moringa oleifera Ameliorate Diclofenac-induced Hepatoxicity in Rats

Hamza¹

2007

American J. of Pharmacology and Toxicology

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Abstract:Although treatment with therapeutic agents may be one of the main causes of liver toxicity, there have been only limited attempts at thorough research efforts to seek solution. Diclofenac (DIC) is a widely used anti-inflammatory drug that causes liver toxicity. This DIC-induced hepatotoxicity was found to be associated with oxidative damage. In this report, extracts of herbal plants that are traditionally used for treating many illnesses were examined, namely Curcuma longa (CL), Glycyrrhiza glabra L (GL) and Moringa oleifera Lam (MO). They all showed a novel hepatoprotective effects against DIC-induced hepatotoxicity in rats. Administration of DIC at 150 mg/kg developed acute hepatic damage, as demonstrated by increased serum alanine aminotransferase (ALT) activity and histopathological changes. In addition, DIC treatment resulted in an increase in the hepatic malonialdehyde level and depletion in total antioxidant capacity, reduced glutathione content, catalase, and superoxide dismutase activities. Treatment with herbal extracts for 30 days before DIC treatment significantly ameliorated the indices of hepatotoxicity induced by DIC. In addition, these herbs alleviated DIC-induced oxidative changes in liver. These results suggest that CL, GL, and MO inhibit DIC-induced hepatotoxicity and might serve as a novel combination chemotherapeutic agent with DIC to limit its free radical-induced organ injury.

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Section: Discussionmentioning

confidence: 97%

Curcuma longa, Glycyrrhiza glabra and Moringa oleifera Ameliorate Diclofenac-induced Hepatoxicity in Rats

Hamza¹

2007

American J. of Pharmacology and Toxicology

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“…The formation of ROS has actually been implicated in indomethacin idiosyncratic toxicity such as bone marrow toxicity or hepatitis (Galati et al, 2002). ROS are inactivated by mitochondrial GSH.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1

Groot

Deen

et al. 2007

Br J Cancer

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Small-cell lung cancers (SCLCs) initially respond to chemotherapy, but are often resistant at recurrence. The non-steroidal anti-inflammatory drug indomethacin is an inhibitor of multidrug resistance protein 1 (MRP1) function. The doxorubicin-resistant MRP1-overexpressing human SCLC cell line GLC 4 -Adr was highly sensitive for indomethacin compared with the parental doxorubicin-sensitive line GLC 4 . The purpose of this study was to analyse the relationship between hypersensitivity to indomethacin and MRP1 overexpression. The experimental design involved analysis of the effect of MRP1 downregulation on indomethacininduced cell survival and apoptosis in GLC 4 -Adr and GLC 4 , using siRNA. In addition the effect of indomethacin on glutathione levels and mitochondrial membrane potential was investigated. Small interfering RNAs directed against MRP1 reduced MRP1 mRNA levels twofold and reduced efflux pump function of MRP1, which was reflected by a 1.8-fold higher accumulation of MRP1 substrate carboxyfluorescein, in si-MRP1 versus si-Luciferase-transfected GLC 4 -Adr cells. Multidrug resistance protein 1 downregulation decreased initial high apoptosis levels 2-fold in GLC 4 -Adr after indomethacin treatment for 24 h, and increased cell survival (IC 50 ) from 22.8±2.6 to 30.4±5.1 mM following continuous indomethacin exposure. Multidrug resistance protein 1 downregulation had no effect on apoptosis in GLC 4 or on glutathione levels in both lines. Although indomethacin (20 mM) for 2 h decreased glutathione levels by 31.5% in GLC 4 -Adr, complete depletion of cellular glutathione by L-buthionine (S,R)-sulphoximine only resulted in a small increase in indomethacin-induced apoptosis in GLC 4 -Adr, demonstrating that a reduced cellular glutathione level is not the primary cause of indomethacin-induced apoptosis. Indomethacin exposure decreased mitochondrial membrane potential in GLC 4 -Adr cells, suggesting activation of the mitochondrial apoptosis pathway. Indomethacin induces apoptosis in a doxorubicin-resistant SCLC cell line through an MRP1-dependent mechanism. This may have implications for the treatment of patients with MRP1-overexpressing tumours.

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“…Recent research has focused on the pro-oxidant property of some NSAIDs. For example, the horseradish peroxidasemediated oxidation of biomolecules like ascorbic acid, NADH and glutathione is promoted when these NSAIDs are added to the reac-tion medium (39). This pro-oxidant activity is based on the accelerated oxidation of these biomolecules by NSAID radicals and on the generation of reactive metabolites by the peroxidase-catalyzed reaction.…”

Section: Discussionmentioning

confidence: 99%

Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

Paino

Ximenes

Fonseca

et al. 2005

Braz J Med Biol Res

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The release of reactive oxygen specie (ROS) by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs) on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM), indomethacin (12 µM), naproxen (160 µM), piroxicam (13 µM), and tenoxicam (30 µM) were incubated at 37ºC in PBS (10 mM), pH 7.4, for 30 min with rat neutrophils (1 x 10 6 cells/ml) stimulated by phorbol-12-myristate-13-acetate (100 nM). The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6). For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6). Using the myeloperoxidase (MPO)/ H 2 O 2 /luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%), indomethacin (97 ± 2, 100 ± 1%), naproxen (56 ± 8, 76 ± 3%), piroxicam (77 ± 5, 99 ± 1%), and tenoxicam (90 ± 2, 100 ± 1%), respectively (N = 3). These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

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Idiosyncratic NSAID drug induced oxidative stress

Cited by 128 publications

References 44 publications

Curcuma longa, Glycyrrhiza glabra and Moringa oleifera Ameliorate Diclofenac-induced Hepatoxicity in Rats

Curcuma longa, Glycyrrhiza glabra and Moringa oleifera Ameliorate Diclofenac-induced Hepatoxicity in Rats

Indomethacin induces apoptosis via a MRP1-dependent mechanism in doxorubicin-resistant small-cell lung cancer cells overexpressing MRP1

Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

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