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

ABSTRACT 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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    • "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. DOI:10.1155/2014/479645
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    • "Cisplatin {cis-diamminedichloroplatinum (II)} is a water-soluble anti-cancer drug formed when a platinum atom is surrounded by chloride and ammonium atoms in the cis position of a horizontal plane [1]. The mechanism of cisplatin action is the interaction of the activated platinum complex with DNA to form both intrastrand and interstrand cross-links, resulting in replication and transcription inhibition, single-and double-stranded breaks and miscoding and induction of apoptosis [2]. "
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    ABSTRACT: Cisplatin, cis-diamminedichloroplatinum (II) is a highly effective drug used to treat several cancers. Unfortunately, it has various clinical side effects affecting many tissues. However, small intestine toxicity induced by cisplatin has been rare reports to date. This study aims to investigate the pathology of small intestine upon cisplatin treatment at various doses using histological techniques. Male Wistar rats were divided into 5 groups: group 1 was intraperitoneally (IP) injected with normal saline; group 2, 3, 4 and 5 were IP injected with cisplatin at doses of 25, 50, 75 and 100 mg/kg body weight (BW), respectively. On day 3, rats were weighed and small intestines were collected. This study found that cisplatin significantly reduces BW at all concentrations compared to saline group. Histological analysis of small intestine induced by cisplatin illustrating various pathologies includes hemodynamic change (hemorrhage), reversible injuries (distortion of mucosal architecture, development of subepithelial space and lifting of epithelial layer from the lamina propria) and irreversible injuries (degenerative changes of villi, sloughing of necrotic villi into intestinal lumina and loss of villi). Additionally, cellular adaptations were also elicited including hyperplasia of lamina propria and columnar epithelium lining villi and atrophy of villi. In conclusion, cisplatin administrations lead to pathologies of small intestine, consequently causing weight loss whose severity depends on its concentrations.
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