The role of lipid peroxidation in the nephrotoxicity of cisplatin

Vermeulen, Nico; Baldew, Glenn S.

doi:10.1016/0006-2952(92)90384-u

Cited by 68 publications

(33 citation statements)

References 24 publications

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“…Since changes of kidney function in response to cisplatin appli cation depend on the chloride status, it has been suggested that cisplatin nephrotoxicity results possibly from activa tion of intrarenal regulatory mechanisms [24], Reduction of glomerular filtration rate may be assumed to be a con- [25,26], It has been suggested that binding of cisplatin to the renal base transport system may account for its nephrotoxicity [27], In addition, results from in vitro studies suggest that cisplatin has pronounced effects on renal transport carrier proteins most probably responsible for a direct toxic influence on tubular function [28]. There is evidence sug gesting that cisplatin exerts nephrotoxic effects by the gen eration of free radicals [8,9], However, although these studies suggest lipid peroxidation as a pathway in the onset of cisplatin-induced renal damage, its causal role in cisplatin nephrotoxicity has been queried [29], In the present study, cisplatin was shown to induce lipid peroxi dation in a concentration-dependent manner and to de crease PAH uptake. Since lipid peroxidation is known to inhibit PAH uptake by renal cortical slices [30], it may be assumed that the cisplatin-induced decrease in PAH up take is due to lipid peroxidation.…”

Section: Discussionmentioning

confidence: 99%

Modification of Cisplatin-Induced Renal p-Aminohippurate Uptake Alteration and Lipid Peroxidation by Thiols, Ginkgo biloba Extract, Deferoxamine and Torbafylline

Inselmann¹,

Blöhmer²,

Kottny³

et al. 1995

Nephron

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To determine whether inhibition of lipid peroxidation modifies cisplatin-induced changes of renal p-aminohippurate (PAH) uptake, we examined the effects of various radical scavengers and torbafylline on cisplatin-induced lipid peroxidation and PAH accumulation changes in rat renal cortical slices. Renal cortical slices were incubated with different cisplatin concentrations (0.3, 0.6, 1.0 mg/ml) in the presence of either glutathione, N-acetylcysteine, the iron chelator deferoxamine, Ginkgo biloba extract or the xanthine derivate torbafylline. Lipid peroxidation monitored as the production of malondialdehyde (MDA) was stimulated by increasing cisplatin concentrations in a dose-related manner. At a cisplatin concentration of 1.0 mg/ml, MDA production was twofold compared to controls (0.69 ± 0.06 vs. 1.36 ± 0.07 nmol/mg; p < 0.05). In turn, cisplatin decreased PAH uptake of kidney slices dose-dependently from 13.3 ± 1.3 to 2.6 ± 0.2 (p < 0.01). All agents tested inhibited cisplatin-induced lipid peroxidation; however, at a cisplatin concentration of 1.0 mg/ml, none of them prevented the decline of cisplatin-induced PAH uptake. Of the agents tested, deferoxamine proved to be the most effective antioxidant, completely inhibiting cisplatin-induced lipid peroxidation but in contrast preventing the decrease in PAH uptake only at a cisplatin concentration of 0.3 mg/ml. No strict association between lipid peroxidation and decline of PAH uptake was found, suggesting that lipid peroxidation may only in part participate in cisplatin-induced alterations of PAH uptake.

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Section: Discussionmentioning

confidence: 99%

Modification of Cisplatin-Induced Renal p-Aminohippurate Uptake Alteration and Lipid Peroxidation by Thiols, Ginkgo biloba Extract, Deferoxamine and Torbafylline

Inselmann¹,

Blöhmer²,

Kottny³

et al. 1995

Nephron

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“…The increase could arise from an increase in the rate of glutathione synthesis, since kidney cells have a high rate of glutathione turnover and can synthesize gluta thione in response to cellular injury [26], The role of lipid peroxidation and its position in the chain of events lead ing to nephrotoxicity, in particular whether it is a cause or consequence of toxicity, remain controversial. Vermeulen and Baldew [27] reported that CDDP did not induce lipid peroxidation in rat kidney microsomes nor did it inhibit the activity of a microsomal glutathione-dependent pro tective factor against lipid peroxides induced by Fe2+ ascorbate. It appears that the increase in lipid peroxides in the kidney is not a direct consequence of CDDP adminis tration.…”

Section: Discussionmentioning

confidence: 99%

Effect of L-Histidinol on Cisplatin Nephrotoxicity in the Rat

Badary¹,

Nagi²,

Al-Sawaf³

et al. 1997

Nephron

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The effect of L-histidinol (LHL) on the acute nephrotoxicity produced by cisplatin (CDDP; 6 mg/kg, i.v.) was investigated in the rat. Intraperitoneal administration of LHL (100 mg/kg × 5 doses, 2 h apart) starting 2 h prior to CDDP single injection produced significant protection of renal function. The attenuation of nephrotoxicity was evidenced by significant reductions in serum urea and creatinine concentrations, decreased polyuria, reduction in body weight loss, marked reduction in urinary fractional sodium excretion and glutathione-S-transferase (GST) activity, and increased urine/serum creatinine ratio as well as increased creatinine clearance. LHL significantly ameliorated the toxic renal biochemical changes induced by CDDP. Renal lipid peroxides, glutathione levels and GST activity showed a marked tendency towards the normal values. Accumulation of platinum in renal tissues was significantly decreased in the presence of LHL. It is concluded that LHL can act as a nephroprotectant, and it is suggested that it would have beneficial effects on the kidney in clinical settings.

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“…These radicals are toxic for the myocardium. Free oxygen radicals may contribute to the adriamycin-induced cardiotoxicity (Vermeulen and Baldew 1992;Minotti et al 1999) by causing diverse oxidative damage on critical cellular components and membrane lipids in cellular organelles, such as plasma membrane and mitochondria (Doroshow and Davies 1986;Dorr et al 1996;Shan et al 1996). Moreover, the production of free oxygen radicals induces lipid peroxidation and oxidative damage in the heart (Lown et al 1982;Keizer et al 1990;Bhanumathi et al 1994;Dragojevic-Simic et al 2004).…”

confidence: 99%

The Protective Effects of Amifostine on Adriamycin-Induced Acute Cardiotoxicity in Rats

Bolaman

Çiçek

Kadıköylü

et al. 2005

Tohoku J. Exp. Med.

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Free oxygen radicals and lipid peroxidation are responsible for adriamycin-induced cardiotoxicity. Amifostine is a scavenger of free radicals and may function as a selective cytoprotective agent. The aim of this study was to investigate the effects of amifostine on adriamycin-induced lipid peroxidation and the levels of protective enzymes in the heart. Male Wistar rats were randomly allocated to three groups: pretreated, untreated, and control (n = 10 in each group). Rats were pretreated with an intraperitoneal injection of amifostine (200 mg/kg) 30 min before the injection of adriamycin. The pretreated rats were given an intraperitoneal injection of adriamycin (10 mg/kg) and were sacrificed after 72 h. Likewise, rats received intraperitoneal injection of adriamycin (untreated) or saline (control). The hearts were removed for the analyses of malondialdehyde (MDA), reduced glutathione (GSH) and catalase. MDA levels were increased ( p < 0.005) in the heart tissues of untreated rats compared to control, while GSH and catalase levels were decreased ( p < 0.05 and p < 0.001, respectively) in untreated animals. In amifostine-preatreated group, MDA levels were lower ( p < 0.01), and GSH and catalase levels were higher ( p < 0.05 for both) than the untreated group. GSH levels were even higher in the amifostine-pretreated group compared to control ( p < 0.01), although catalase levels were significantly lower in the pretreated group ( p < 0.05). These results indicate that amifostine decreases adriamycin-induced lipid peroxidation and increases the levels of the protective enzymes in the heart tissue. Therefore, amifostine may ameliorate the adriamycin-induced acute cardiotoxicity.

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The role of lipid peroxidation in the nephrotoxicity of cisplatin

Cited by 68 publications

References 24 publications

Modification of Cisplatin-Induced Renal <i>p</i>-Aminohippurate Uptake Alteration and Lipid Peroxidation by Thiols, <i>Ginkgo biloba</i> Extract, Deferoxamine and Torbafylline

Modification of Cisplatin-Induced Renal <i>p</i>-Aminohippurate Uptake Alteration and Lipid Peroxidation by Thiols, <i>Ginkgo biloba</i> Extract, Deferoxamine and Torbafylline

Effect of <i>L</i>-Histidinol on Cisplatin Nephrotoxicity in the Rat

The Protective Effects of Amifostine on Adriamycin-Induced Acute Cardiotoxicity in Rats

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