Quercetin and hyperthermia modulate cisplatin-induced DNA damage in tumor and normal tissues in vivo

Abstract

Nephrotoxicity, hepatotoxicity, myelosuppression, and genotoxicity are the major limitation for the clinical use of cisplatin as an anti-tumoural drug. Hyperthermia enhances the clastogenicity of cisplatin. In addition, hyperthermia is a promising approach for cancer therapy because it not only kills cancer cells directly, but also activates anti-cancer immunity as an indirect effect. The aim of this study was to determine whether preventive treatment with quercetin (QU) can reduce cisplatin-induced DNA damage in liver, kidney and blood cells and whether QU has the potential to serve as a beneficial supplement before cisplatin hyperthermal intraperitoneal chemotherapy (HIPEC) in order to gain immunomodulatory responses of mice to the tumor. Preventive treatment of mice with QU (50 mg kg(-1)) had a protective effect on cisplatin-induced DNA damage in normal cells, except kidney cells, in both normothermic and hyperthermic conditions without interfering with the antitumor efficacy of the combined regimen. Immunostimulation by QU is stressed as an important factor in the tumor-inhibiting effect of hyperthermia in addition to the well known selective heat killing of neoplastic cells. In conclusion, these results suggested that preventive treatment with QU could protect the blood, liver and kidney cells of mice against HIPEC-induced injury and increase survival of mice by improving the antitumor adaptive immunity with hyperthermia.

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

“…The final concentration of ethanol was equal to 0.5% (v/v). Quercetin was given to mice by ig application every day for 15 days at a dose of 50 mg kg −1 body weight (Benkovic et al, 2008;Oršolić et al, 2007Oršolić et al, , 2010Oršolić et al, , 2011Oršolić & Car, 2014;Sirovina et al, 2013).…”

“…It was also suggested that quercetin acts as an antioxidant by inhibiting xanthine oxidase, lipoxygenase and NADPH oxidase, oxidative enzymes that play key roles in the initial process of free radical-induced cellular damage (Benkovic et al, 2008;Moskaug, Carlsen, Myhrstad, & Blomhoff, 2004;Oršolić et al, 2007Oršolić et al, , 2010Oršolić et al, , 2011Oršolić & Car, 2014;Sirovina et al, 2013). In addition, much attention has been focused on the influence of quercetin on signaling pathways and its indirect interaction with the endogenous antioxidant defense system (Oršolić & Car, 2014;Sirovina et al, 2013) such as phase I and II detoxifying enzymes, and its ability to increase the expression of the rate limiting enzyme c-glutamylcysteine synthetase in the synthesis of glutathione (GSH) and induce xenobiotic responsive elements in CYP 450 family genes (Myhrstad, Carlsen, Nordström, Blomhoff, & Moskaug, 2002;Yao et al, 2007).…”

“…In addition, much attention has been focused on the influence of quercetin on signaling pathways and its indirect interaction with the endogenous antioxidant defense system (Oršolić & Car, 2014;Sirovina et al, 2013) such as phase I and II detoxifying enzymes, and its ability to increase the expression of the rate limiting enzyme c-glutamylcysteine synthetase in the synthesis of glutathione (GSH) and induce xenobiotic responsive elements in CYP 450 family genes (Myhrstad, Carlsen, Nordström, Blomhoff, & Moskaug, 2002;Yao et al, 2007). Furthermore, Yao et al (2007) demonstrated that plant-derived flavonoids or polyphenols, including quercetin, may act as non-stressful and non-cytotoxic heme oxigenase-1 (HO-1) inducers maximizing cellular intrinsic antioxidant potential, while Morales et al (2006) suggested that renal protection exerted by quercetin is based on its ability to increase metallothionein in kidneys.…”

Flavones and Flavonols may have Clinical Potential as CK2 Inhibitors in Cancer Therapy

“…(The "flip side" of this observation is that quercetin has potential for protecting healthy tissues from chemotherapy drugs, as demonstrated in mice. [177][178][179][180][181] These considerations, in any case, do not speak to quercetin's potential utility as an adjuvant for slowing cancer growth.…”

Effect of Quercetin on Bone Mineral Status and Markers of Bone Turnover in Retinoic Acid-Induced Osteoporosis

“…It has been reported that quercetin inhibits bone loss in rat model of diabetic osteopenia and exerts protective effects against β-cell damage in diabetes [Coskun et al, 2005;Oršolić et al, 2011]. Quercetin is a powerful natural antioxidant and can protect many types of tissue or organs against oxidative damage, including liver, kidney and pancreatic gland [Knežević et al, 2011;Oršolić et al, 2011Oršolić et al, , 2016Oršolić & Car, 2014]. Furthermore, quercetin has beneficial effects on bone cells and tissues and it is capable of inhibiting bone loss in ovariectomized mice [Tsuji et al, 2009] and retinoic acid-induced bone loss .…”