Diclofenac Sodium and Mefenamic Acid: Potent Inducers of the Membrane Permeability Transition in Renal Cortex Mitochondria

Uyemura, Sérgio Akira; Santos, Antônio Carlos dos; Mingatto, Fábio Ermínio; Jordani, Maria Cecília; Curti, Carlos

doi:10.1006/abbi.1997.9985

Cited by 78 publications

(40 citation statements)

References 30 publications

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“…A few earlier studies have also suggested that lipid peroxidation may not play a causative role in the pathogenesis of paracetamol-induced renal injury. 41,42 Depletion of glutathione may not be the only mechanism of paracetamol-induced renal injury. Paracetamol-induced renal injury could also be due to hepatic-derived paracetamol metabolites, particularly glutathione conjugates, 43 and inhibition of renal organic anion transporter.…”

Section: Discussionmentioning

confidence: 98%

Vitamin C may be beneficial in the prevention of paracetamol-induced renal damage

Abraham

2005

Clin Exp Nephrol

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Section: Discussionmentioning

confidence: 98%

Vitamin C may be beneficial in the prevention of paracetamol-induced renal damage

Abraham

2005

Clin Exp Nephrol

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“…In studies carried out in artificial lipid bilayers (15,18), in cell membranes (18,30,35), and in isolated mitochondria (10,11,34,52), it was demonstrated that NSAIDs at concentrations in the high micromolar range may impair membrane permeability for ions and small molecules. In connection with this, we hypothesized that a potential increase in passive H ϩ permeability of cell membranes elicited by NSAIDs would dissipate the H ϩ gradient generated by the H ϩ -K ϩ -ATPase activity, resulting in a blockade of gastric acid formation.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism

Salvatella¹,

Rossi²,

Valle³

et al. 2004

American Journal of Physiology-Gastrointestinal and Liver Physi

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In nonstimulated rabbit gastric glands, acetylsalicylic acid (10-500 microM) and indomethacin (3-300 microM) did not significantly modify the basal rate of acid secretion, whereas diclofenac and piroxicam (10-1,000 microM each) caused a marked and dose-dependent inhibitory effect (EC(50) = 138 and 280 microM, respectively). In gastric glands stimulated by histamine (100 microM), diclofenac also reduced the rate of acid formation in a dose-dependent manner. In contrast, acetylsalicylic acid, indomethacin, and piroxicam exerted a biphasic effect; thus low concentrations (3-100 microM) of these three agents significantly increased the rate of histamine-stimulated acid secretion (10-20% over the corresponding control value) by a cAMP-independent mechanism, whereas higher concentrations reduced the rate of acid formation. With respect to underlying biochemical mechanisms that could mediate inhibitory effects of NSAIDs on gastric acid formation, it was observed that both diclofenac and piroxicam, but not acetylsalicylic acid or indomethacin, decreased the glandular content of ATP, inhibited hydrolytic activity of gastric gland microsomal H(+)-K(+)-ATPase, and reduced the rate of H(+)-K(+)-ATPase-dependent proton transport across microsomal membranes in a dose-dependent manner. Furthermore, diclofenac and piroxicam also significantly increased passive permeability of microsomal membranes to protons. In conclusion, our work shows that diclofenac and piroxicam cause a significant reduction in the rate of basal and histamine-stimulated acid formation in isolated rabbit gastric glands at concentrations that can be attained in the gastric lumen of patients treated with these drugs. Mechanisms involved in these inhibitory effects appear to be multifocal and include different steps of stimulus-secretion coupling.

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“…This could be explained on the basis of the fact that the liver is capable of synthesizing glutathione from precursors and, in fact, the liver is the main producer and exporter of glutathione [42,43]. The kidney, on the other hand, cannot synthesize glutathione from its precursors and is dependent on plasma for its requirement [43].…”

Section: Discussionmentioning

confidence: 99%

Melatonin prevents acetaminophen-induced nephrotoxicity in rats

İlbey¹,

Özbek²,

Çekmen³

et al. 2009

Int Urol Nephrol

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Nephrotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug, and there is no specific treatment for APAP-induced renal damage. It has been reported that reactive oxygen metabolites or free radicals are important mediators of APAP toxicity. In this study, the protective role of melatonin (MLT) on APAP-induced nephrotoxicity was investigated in rats. For this purpose, nephrotoxicity was induced in male Wistar albino rats by intraperitoneal (i.p.) administration of a single dose of 1,000 mg/kg APAP. Some of these rats also received i.p. melatonin (10 mg/kg) 20 min after administration of APAP. The rats were sacrificed 24 h after administration of APAP. Urea and creatinine levels were measured in the blood, and levels of malondialdehyde (MDA) and glutathione (GSH), and glutathione peroxidase (GSH-Px), catalase (CAT), and superoxide dismutase (SOD) activity were determined in renal tissue. Serum urea and creatinine levels increased significantly as a result of APAP nephrotoxicity. A significant increase in MDA and decreases in GSH level and GSH-Px, CAT, and SOD activity indicated that APAP-induced renal damage was mediated through oxidative stress. Significant beneficial changes were noted in serum and tissue oxidative stress indicators in rats treated with MLT. These biochemical observations were supplemented by histopathological examination of kidney sections, which revealed that MLT also reduced the severity of APAP-induced histological alterations in the kidney. These results indicate that administration of APAP causes oxidative stress to renal tissue and that MLT protects against the oxidative damage associated with APAP.

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Diclofenac Sodium and Mefenamic Acid: Potent Inducers of the Membrane Permeability Transition in Renal Cortex Mitochondria

Cited by 78 publications

References 30 publications

Vitamin C may be beneficial in the prevention of paracetamol-induced renal damage

Vitamin C may be beneficial in the prevention of paracetamol-induced renal damage

Inhibition of acid secretion by the nonsteroidal anti-inflammatory drugs diclofenac and piroxicam in isolated gastric glands: analysis of a multifocal mechanism

Melatonin prevents acetaminophen-induced nephrotoxicity in rats

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