Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: a review of some recent research. Food Chem Toxicol

Department of Medicine, Sultan Qaboos University, Masqaţ, Muḩāfaz̧at Masqaţ, Oman
Food and Chemical Toxicology (Impact Factor: 2.9). 09/2006; 44(8):1173-83. DOI: 10.1016/j.fct.2006.01.013
Source: PubMed


Cisplatin (cis-diamminedichloroplatinum (II)) is an effective agent against various solid tumours. Despite its effectiveness, the dose of cisplatin that can be administered is limited by its nephrotoxicity. Hundreds of platinum compounds (e.g. carboplatin, oxaliplatin, nedaplatin and the liposomal form lipoplatin) have been tested over the last two decades in order to improve the effectiveness and to lessen the toxicity of cisplatin. Several agents have been tested to see whether they could ameliorate or augment the nephrotoxicity of platinum drugs. This review summarizes these studies and the possible mechanisms of actions of these agents. The agents that have been shown to ameliorate experimental cisplatin nephrotoxicity include antioxidants (e.g. melatonin, vitamin E, selenium, and many others), modulators of nitric oxide (e.g. zinc histidine complex), agents interfering with metabolic pathways of cisplatin (e.g. procaine HCL), diuretics (e.g. furosemide and mannitol), and cytoprotective and antiapoptotic agents (e.g. amifostine and erythropoietin). Only few of these agents have been tested in humans. Those agents that have been shown to augment cisplatin nephrotoxicity include nitric oxide synthase inhibitors, spironolactone, gemcitabine and others. Combining these agents with cisplatin should be avoided.

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Available from: Badreldin H. Ali, May 22, 2015
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    • "This result is also consistent with (Nabila et al., 2008), who found a strong positive correlation between the content of total phenolics and FRAP assay. All of these studies were based on the assumption that GA has strong anti-oxidant, and a major mechanism for the induction of these toxicities is the generation of free radicals (Benzie and Stezo., 1999) and (Ali and Al Moundhri ., 2006). "
    08/2015; 6(1):127. DOI:10.5296/jbls.v6i1.6818
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    • "Distal tubular cells were also affected. Consistent with the results of the present study, Mansour et al. [6]; Abdelmaguid et al. [27], Nasr [18]; Ali and Al-Moundhri, [28]; Chirino et al. [29] reported similar findings in rats exposed to different doses of CP. "
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    ABSTRACT: Cisplatin (CP) is one of the effective anticancer drugs, but it causes many side effects. Aged garlic extract (AGE) is a natural herbal product used in management of many diseases. This study aimed to investigate effect of AGE on CP-induced nephrotoxicity in rats. Material and methods Four equal groups of adult male rats: control, AGE -treated (250 mg/kg, once oral dose/ 21days), CP-treated (7.5 mg/kg once i.p. on day 16th.), combined AGE and CP-treated were used. Body and kidneys weights of each rat were calculated. Serum levels of kidney biomarkers were assessed. Malondialdehyde (MDA) and reduce glutathione (GSH) levels, superoxide dismutase (SOD) and catalase (CAT) activities of renal tissues were measured as well. Renal samples from each rat were prepared for light and electron microscopic examinations. Hemorrhage, glomerular atrophy, inflammatory cell infiltration, tubular necrosis and degeneration were observed in CP-treated rats. Also, a significant (P<0.001) reduction in SOD & CAT activities, GSH levels accompanied with a significant increase in serum levels of kidney biomarkers and MDA were determined in CP-treated rats compared to control group. However, most of CP-induced histomorphological, ultrastructural and biochemical changes were improved in animals pretreated with AGE. Such renoprotective effect of AGE may be attributed to its antioxidant activity.
    Cancer Cell International 09/2014; 14(1):92. DOI:10.1186/s12935-014-0092-x · 2.77 Impact Factor
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    • "Inflammation, oxidative stress, and change in the renal circulation may also be induced by CDDP [4] [5] [6]. To decline CDDP-induced nephrotoxicity, recent studies have concentrated on many supplementations [7] [8] [9] [10] [11]. Losartan is an angiotensin type-1 receptor blocker as well as an antioxidant, which has been suggested to be nephroprotective against CDDP-induced nephrotoxicity by others [10] [11]. "
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    ABSTRACT: Background. Cisplatin (CDDP) is an anticancer drug, which is accompanied with major side effects including nephrotoxicity. We tested two doses of losartan (10 and 20 mg/kg/day) against nephrotoxicity in a rat model treated with daily administration of CDDP (2.5 mg/kg/day). Methods. Five groups of rats were examined. Groups 1 and 2 received losartan 10 and 20 mg/kg/day, i.p, for a period of 10 days. Group 3 received saline for 10 days, but from day 3 the animals received CDDP (2.5 mg/kg/day, i.p) for the next seven days. Groups 4 and 5 received treatment regimen the same as groups 1 and 2, but from day 3 they also received CDDP for the next seven days. At the end of the experiment, blood samples were obtained and the kidneys were removed to undergo pathological investigation and to obtain supernatant from homogenized tissue. Results. CDDP induced nephrotoxicity, but the serum levels of creatinine and blood urea nitrogen were not attenuated by losartan. The pathological findings confirmed that losartan did not have nephroprotective effect in this experimental model.Conclusion. According to the findings, losartan could not improve renal function impaired by toxicity induced by continuous doses of CDDP, and also it worsened the renal failure.
    03/2014; 2014(1). DOI:10.1155/2014/479645
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