Evidence for the involvement of nitric oxide in cisplatin-induced toxicity in rats

Srivastava, R.C.; Farookh, Aziz; Ahmad, Nihal; Misra, M. K.; Hasan, Syed Kazim; Husain, Maroof

doi:10.1007/bf00144618

Cited by 79 publications

(50 citation statements)

References 18 publications

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“…The interaction of ROS with cellular components may result in damage to biomolecules, including DNA, proteins, and lipids. Cisplatin treatment also induces a significant increase in the activity of calcium-independent nitric oxide synthase in rat kidney and liver tissues, resulting in an increase in serum NO levels as well as in tissue NO formation (40,41). Peroxynitrite, which is generated by the reaction between nitric oxide and superoxide anion, also oxidizes biomolecules.…”

Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Tumor Growth and Protects the Kidney and Liver Against Chemotherapy-Induced Toxicity in a Mouse Xenograft Model of Colon Carcinoma

et al. 2008

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Abstract. A growing amount of attention has been focused on the investigation of the effects of chemopreventive agents on the inhibition of cancer cell growth and toxicity in combination with chemotherapeutics. The objective of this study was to determine whether isoliquiritigenin (ISL) has the potential to serve as a beneficial supplement during cisplatin chemotherapy. We found that the administration of ISL alone significantly reduced the size of the solid tumors in CT-26 cell-inoculated BALB / c mice, without any detectable induction of nephrotoxicity, hepatotoxicity, and oxidative stress, and ISL reduced the viability and DNA synthesis of CT-26 murine colon cancer cells in a dose-dependent manner. ISL did not affect the therapeutic efficacy of cisplatin. Furthermore, ISL suppressed cisplatin-induced kidney damage characterized by increases in serum creatinine and blood urea nitrogen, as well as cisplatin-induced liver damage characterized by increases in serum alanine aminotransferase and aspartate aminotransferase. The repeated oral administration of ISL prior to cisplatin treatment exerted a preventive effect on cisplatin-mediated increases in serum nitric oxide and tissue lipid peroxidation levels, and it recovered depleted GSH levels in the tissues. Therefore, supplementation with ISL may be an effective approach to counteracting the side effects of cisplatin therapy in cancer patients.

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Section: Discussionmentioning

confidence: 99%

Isoliquiritigenin Inhibits Tumor Growth and Protects the Kidney and Liver Against Chemotherapy-Induced Toxicity in a Mouse Xenograft Model of Colon Carcinoma

et al. 2008

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“…Cisplatin treatment also causes a significant increase in the activity of the calcium-independent nitric oxide synthase (NOS) in rat kidney and liver, leading to an increase in serum NO level as well as in tissue NO formation. 30,31) Peroxynitrite, generated by the reaction between nitric oxide and superoxide anion, oxidizes biomolecules such as DNA, proteins and lipids. In the present study, the oral administration of the licorice extract in combination with the cisplatin treatment prevented the increases in the serum nitric oxide and tissue lipid peroxidation levels, and significantly recovered the tissue GSH level and antioxidant enzyme activities in the cisplatin-treated mice.…”

Section: Discussionmentioning

confidence: 99%

Effects of the Licorice Extract against Tumor Growth and Cisplatin-Induced Toxicity in a Mouse Xenograft Model of Colon Cancer

Lee

Park

Lim

et al. 2007

Biological & Pharmaceutical Bulletin

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Cisplatin (cis-diamminedichloroplatinum II) is a platinum coordinated complex that is widely used as an antineoplastic agent for the treatment of many solid tumors, including cancers of the ovary, testis, lung, bladder, head and neck, cervix and endometrium.1) Despite its excellent anticancer activity, the clinical use of cisplatin is often limited by its undesirable side effects, such as severe nephrotoxicity and hepatotoxicity. 2,3) Although the precise mechanism for this cisplatin-induced toxicity is not well understood, cisplatin is taken up preferentially and accumulates in the human liver and kidney cells, 4) resulting in the enhanced production of reactive oxygen species (ROS) and the decrease in the antioxidant enzymes.5,6) Therefore, antioxidants have been administered before a cisplatin treatment to protect against nephrotoxicity. 7)Licorice is an esteemed crude drug in both the Orient and Occident that is originated from the dried roots of several Glycyrrhiza species, including Glycyrrhiza uralensis FISCHER, G. glabra LINNE and G. inflata BATALIN. 8,9) In Chinese traditional medicine, licorice remains one of the most commonly prescribed herbs and has been used in the treatment of various ailments ranging from tuberculosis to peptic ulcers.10) Licorice has also been employed as a flavoring and sweetening agent, as well as a demulcent and expectorant in Western countries.11) The chemical constituents of licorice include glycyrrhizin and its aglycone, glycyrrhetinic acid, which are originally isolated from aqueous extracts and are used in the treatment of hyperlipemia, atherosclerosis, viral diseases, allergic inflammation and hepatotoxicity.12,13) The acetone or ethanol extract of licorice has species-specific flavonoids, such as liquiritin, isoliquiritin and their corresponding aglycones, glabridin, glabrol, glabrene, hispaglabridin A and hispaglabridin B.14,15) These flavonoids exhibit antioxidative, 16) superoxide scavenging 16) and anticarcinogenic activities.17) However, in vivo antitumor activity of a licorice extract and its protective activity on cisplatin-induced toxicity have not yet been studied.In the present study to assess the antitumor activity of a licorice extract and whether it has the potential to serve as a beneficial supplement during cisplatin chemotherapy, we examined the inhibitory effect of the licorice extract alone and in combination with cisplatin on the tumor growth, and its protective effect against cisplatin-induced nephrotoxicity and hepatotoxicity in mice xenografted with mouse colon carcinoma cells. MATERIALS AND METHODSChemical Cisplatin, phenylmethylsulfonyl fluoride (PMSF), sodium nitrite, 1,1,3,3-tetramethoxypropane, reduced glutathione (GSH), 5,5Ј-dithiobis(2-nitrobenzoic acid) (DTNB), glutathione reductase, reduced nicotinamide adenine dinucleotide phosphate (NADPH), superoxide dismutase (SOD), xanthine oxidase, a-naphthylamine, sulfanilic acid, xanthine, catalase and 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (purpald ® ) were purchased from SigmaAldrich Chem...

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“…This suggests that inhibition of these enzymes may lead to an increase in levels of arginine, an immediate substrate for nitric oxide synthase (NOS), producing a nitric oxide (NO) precursor that can lead to the formation of NO. A role for NO has been implicated in models of renal injury (Srivastava et al 1996), and L-arginine has been demonstrated to be both protective (Andoh et al 1997) and harmful (Tome et al 1999) in models of renal injury. The authors speculate that although the initial effects of NO formation after renal injury may be beneficial, the prolonged inhibition of the L-arginine pathway may contribute to renal damage because of excessive buildup of NO, which has been implicated in numerous renal pathologies (Valdivielso and Blantz 2002).…”

Section: Discussionmentioning

confidence: 99%

Identification of Putative Gene Based Markers of Renal Toxicity

Amin¹,

Vickers²,

Sistare³

et al. 2004

Environ. Health Perspect.

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This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants-cisplatin, gentamicin, and puromycin-to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity.

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Evidence for the involvement of nitric oxide in cisplatin-induced toxicity in rats

Cited by 79 publications

References 18 publications

Isoliquiritigenin Inhibits Tumor Growth and Protects the Kidney and Liver Against Chemotherapy-Induced Toxicity in a Mouse Xenograft Model of Colon Carcinoma

Isoliquiritigenin Inhibits Tumor Growth and Protects the Kidney and Liver Against Chemotherapy-Induced Toxicity in a Mouse Xenograft Model of Colon Carcinoma

Effects of the Licorice Extract against Tumor Growth and Cisplatin-Induced Toxicity in a Mouse Xenograft Model of Colon Cancer

Identification of Putative Gene Based Markers of Renal Toxicity

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