Effect of Naringin on the DNA Damage Induced by Daunorubicin in Mouse Hepatocytes and Cardiocytes

Abstract

Naringin (Nar) is a flavonoid that has shown antigenotoxic effect against the chromosome damage induced by various compounds. The aims of the present investigation on Nar were threefold: a) to determine its DNA breaking potential in mouse hepatocytes and cardiocytes, b) to evaluate its capacity to inhibit the DNA damage induced by daunorubicin (Dau) in the same tissues, and c) to determine its capacity to trap free radicals in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method. For the two first purposes we applied the comet assay to three groups of animals administered with Nar by the oral route (50, 250, 500 mg/kg), and made the observations before the chemical administration and at 3, 12, and 21 h postadministration. Other three groups of mice were given equal doses of Nar, and 1 h later they were intraperitoneally injected with 1 mg/kg of Dau. The results showed that Nar did not induce DNA breakage in both types of studied cells, in contrast with the significant damage induced by Dau in hepatocytes and cardiocytes. Moreover, the administration of Nar protected the DNA damage produced by Dau, showing a maximum reduction of 71.3% and 51.1% in hepatocytes and cardiocytes, respectively. With respect to the antioxidant potential, 20 mM of Nar produced a free radical scavenging activity as high as 95%. Our study established a high DNA breaking potential of Dau, and a protective effect by Nar, probably related with its capacity to trap free radicals.

Nucleophosmin modulates stability, activity, and nucleolar accumulation of base excision repair proteins

“…If we consider the nucleolus as a storage depot, our data would point to the redistribution of BER proteins as a means of increasing the nucleoplasmic repair capacity. A possible contribution of the BER pathway in repairing damage induced by cisplatin (as already suggested; Wilson and Seidman, 2010; Kothandapani and Patrick, 2013), daunorubicin, or actinomycin D is conceivable, as all of these agents have been reported to promote accumulation of oxidative stress and markers of DNA strand breaks (Ali et al ., 2002; Mischo et al ., 2005; Cariño-Cortés et al ., 2010). Despite numerous studies reporting NPM1 relocalization upon nucleolar stress, there is little evidence supporting this model for classic BER-related agents (e.g., alkylating compounds or H 2 O 2 ).…”

Aqueous Fenugreek Seed Extract Ameliorates Adriamycin-Induced Cytotoxicity and Testicular Alterations in Albino Rats

“…Administration of naringin protected the DNA damage produced by ADR in mouse hepatocytes and cardiocytes. 44 Other plant flavonoids, like vicenin and orientin, have also been reported to protect mouse bone marrow cells against radiationinduced chromosome aberrations. 45 Administration of fenugreek seed extract ameliorates ADRinduced histopathological alterations in testes of rats.…”

Preclinical Evidence for the Pharmacological Actions of Naringin: A Review

“…Likewise, naringin at a dose of 100-400 mg/kg has also been shown to ameliorate ferric-nitrilotriacetate and glycerolinduced nephrotoxicity in rats via normalizing plasma creatinine, blood urea nitrogen, urea clearance, and bolstering renal antioxidant levels [76,77]. Naringin (50-500 mg/kg) also prevented the cardiomyocyte and hepatocyte DNA damage produced by daunorubicin in mice, probably due to its strong capacity to trap free radicals [78]. It (5-50 mg/kg) has also been shown to have a protective role in the abatement of lomefloxacin-induced genomic instability in mice, most likely due to its antioxidant effects [79].…”