Novel mechanisms of nonsteroidal anti-inflammatory drug-induced renal toxicity

Knights, Kathleen M.; Tsoutsikos, Paraskevi; Miners, John O.

doi:10.1517/17425255.1.3.399

Cited by 25 publications

(12 citation statements)

References 53 publications

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“…Several research studies developed over the past 15 years reported the evidence of NSAIDs-induced kidney dysfunctions, such as acute renal failure and electrolyte imbalance. Nonetheless, the exact mechanism(s) of nephrotoxicity remains still unclear, though most theories focus on the initial inhibition of the cyclooxygenase (COX), the enzyme involved in prostaglandins (PG) synthesis, producing vasoconstriction and the subsequent perturbation of the numerous actions of COX in the kidney [30]. …”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

et al. 2011

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Medication-overuse headache (MOH) is a chronic disorder associated with overuse of analgesic drugs, triptans, non-steroidal anti-inflammatory drugs (NSAIDs) or other acute headache compounds. Various epidemiologic investigations proved that different drug types could cause nephrotoxicity, particularly in chronic patients. The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of MOH patients focusing on daily use of NSAIDs, mixtures and triptans that could reasonably be related to potential renal damage. We selected 43 MOH patients overusing triptans (n = 18), NSAIDs (n = 11), and mixtures (n = 14), for 2–30 years with a mean daily analgesic intake of 1.5 ± 0.9 doses, and a control group composed of 16 healthy volunteers. Urine proteins were analyzed by mono-dimensional gel electrophoresis and identified by mass spectrometry analysis. Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53–948.67 vs. controls; OR = 11.6, 95% CI 0.92–147.57 vs. triptans and mixtures groups). Six of these proteins (uromodulin, α-1-microglobulin, zinc-α-2-glycoprotein, cystatin C, Ig-kappa-chain, and inter-α-trypsin heavy chain H4) were strongly correlated with various forms of kidney disorders. Otherwise, in mixtures and in triptans abusers, only three proteins were potentially associated to pathological conditions (OR = 4.2, 95% CI 0.33–53.12, vs. controls). In conclusion, this preliminary proteomic study allowed us to define the urinary protein pattern of MOH patients that is related to the abused drug. According with the obtained results, we believe that the risk of nephrotoxicity should be considered particularly in MOH patients who abuse of NSAIDs.

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Section: Discussionmentioning

confidence: 99%

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

et al. 2011

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“…The use of NSAIDs is associated with various side effects, including gastrointestinal, renal, hepatic and allergic effects. [1][2][3][4] In addition, recent studies have shown that the benefits of NSAID use include the prevention of the development of colorectal cancer and Alzheimer's disease. [5,6] The pharmaceutical actions of all NSAIDs are believed to occur through the inhibition of prostaglandin (PG) synthesis by prostaglandin H synthase (PGHS), which is responsible for prostaglandin synthesis.…”

Section: Introductionmentioning

confidence: 99%

Reactivity of nonsteroidal anti-inflammatory drugs with peroxidase: a classification of nonsteroidal anti-inflammatory drugs

Miura

2012

Journal of Pharmacy and Pharmacology

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“…1 However the use of this drug has been implicated in some cases of nephrotoxicity. 2 Due to the importance of the assay of FFA for pharmaceutical formulations and biological fluids, several analytical methods have been developed for the quantitative determination of this drug in both pharmaceutical and biological samples.…”

Section: Introductionmentioning

confidence: 99%

“…The aim of the present contribution was to develop a simple and low-cost potentiometric flufenamate ISE immobilized in a graphite matrix (Pt Hg Hg 2 (FF) 2 Graphite, where FF stands for flufenamate ion) and to evaluate the applicability of this sensor to the determination of FFA in dosage forms and human serum samples.…”

Section: Introductionmentioning

confidence: 99%

Development of a potentiometric flufenamate ISE and its application to pharmaceutical and clinical analyses

Santini¹,

Pezza²,

Oliveira³

et al. 2008

J. Braz. Chem. Soc.

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As características, o desempenho e a aplicação de um eletrodo do tipo Pt Hg Hg 2 (FF) 2 Grafite, FF=íon flufenamato, são descritas. O eletrodo responde a FF com sensibilidade de (-58,6 1,2) mV década -1 no intervalo de 1,0 10 -6 -1,0 10 -2 mol L -1 , a pH 6,0 -9,0 e com um limite de detecção de 7,1 10 -7 mol L -1 . O eletrodo é de custo relativamente baixo e facilmente construído, apresenta um rápido tempo de resposta (10-25 s) e pode ser usado por um período de 5 meses sem qualquer variação considerável nas suas características de desempenho. O eletrodo proposto mostrou boa seletividade para o íon flufenamato na presença de várias substâncias, bem como na presença de alguns carboxilatos e ânions inorgânicos. O eletrodo foi aplicado com sucesso na determinação de ácido flufenâmico em medicamentos e amostras de soro humano.The characteristics, performance, and application of an electrode, namely, Pt Hg Hg 2 (FF) 2 Graphite, where FF stands for flufenamate ion, are described. This electrode responds to FF with sensitivity of (-58.6 1.2) mV decade -1 over the range 1.0 10 -6 -1.0 10 -2 mol L -1 at pH 6.0 -9.0 and a detection limit of 7.1 10 -7 mol L -1. The electrode is easily constructed at a relatively low cost with fast response time (within 10-25 s) and can be used for a period of 5 months without any considerable change in its performance characteristics. The proposed electrode displayed good selectivity for flufenamate in the presence of several substances as well as in the presence of some carboxylate and inorganic anions. The electrode was successfully applied to the determination of flufenamic acid in pharmaceuticals and human serum samples.Keywords: flufenamate-sensitive electrode, potentiometry, dosage forms, blood serum IntroductionFlufenamic acid (FFA), [N-( , , -trifluoro-m-tolyl) anthranilic acid] is an analgesic, anti-inflammatory and antipyretic drug. It is extensively used in the treatment of arthritis and other illnesses related to muscular-skeletal problems.1 However the use of this drug has been implicated in some cases of nephrotoxicity.2 Due to the importance of the assay of FFA for pharmaceutical formulations and biological fluids, several analytical methods have been developed for the quantitative determination of this drug in both pharmaceutical and biological samples.These methods include spectrophotometry, 21,22 However, many of these methods are often time-consuming, technically demanding and require the use of costly, highly specialized instruments. Thus, there is an important demand for simple, low-cost, sensitive and rapid alternative methods for the determination of FFA in pharmaceuticals and biological fluids.Potentiometric methods with ion-selective electrodes (ISE's) have proved to be effective for the analysis of pharmaceutical formulations and biological samples, because these sensors offer the advantages of simple design, construction, and manipulation, reasonable selectivity, fast response time, applicability to colored and turbid solutions and possible interfacing with au...

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Novel mechanisms of nonsteroidal anti-inflammatory drug-induced renal toxicity

Cited by 25 publications

References 53 publications

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages

Reactivity of nonsteroidal anti-inflammatory drugs with peroxidase: a classification of nonsteroidal anti-inflammatory drugs

Development of a potentiometric flufenamate ISE and its application to pharmaceutical and clinical analyses

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