Copper and Resveratrol Attenuates Serum Catalase, Glutathione Peroxidase, and Element Values in Rats with DMBA-Induced Mammary Carcinogenesis

Abstract

In this paper, a hypothesis was assessed whether or not the intoxication with copper and supplementation with copper plus resveratrol would result in changes in the activities of catalase and glutathione peroxidase and moreover if the characteristic changes would appear in concentrations of copper, iron, calcium, magnesium, and zinc in the serum of rats with chemically induced carcinogenesis. Female Sprague-Dawley rats were divided into study groups which, apart from the standard diet, were treated with copper (42.6 mg Cu/kg food as CuSO4·5H2O) or copper plus resveratrol (0.2 mg/kg body) via gavage for a period from 40 days until 20 weeks of age. In cancer groups, the rats were treated with a dose of 80 mg/body weight of 7,12-dimethyl-1,2-benz[a]anthracene (DMBA) given in rapeseed oil at 50 and 80 days of age to induce mammary carcinogenesis. The control groups included the rats kept in the same conditions and fed with the same diet as the animals from the study groups, but not DMBA-treated. The activity of catalase significantly decreased in groups of rats with mammary carcinogenesis that were supplemented with copper (p < 0.05) or copper plus resveratrol (p < 0.001) in comparison with the control groups that received the same diets. In cancer groups of nonsupplemented rats, the increase of glutathione peroxidase activity was observed. The process of carcinogenesis and the applied supplementation significantly altered the concentrations of trace elements in serum, in particular as concerns iron and copper. The mean serum iron levels in rats with breast cancer were significantly lower than those in the control groups (p < 0.001). The mean serum copper levels significantly decreased in the groups of rats with mammary carcinogenesis that were supplemented with copper or copper plus resveratrol in comparison with the control groups that received the same diets (p < 0.001). The characteristic changes in iron content and the zinc/copper and zinc/iron ratios in blood may be used as one of the prognostic factors in breast cancer research.

Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort

“…Copper, as a limiting factor, has multifaceted roles in cancer progression, including growth, angiogenesis and metastasis . Preclinical studies have demonstrated that copper supplementation in rodent models significantly enhanced mammary, pancreatic, and lung cancer growth . In addition, copper can regulate the expression and secretion of angiogenic molecules (e.g., vascular endothelial growth factor [VEGF], interleukin‐1alpha [IL‐1α], and fibroblast growth factors [FGFs]), and enhance the affinity of angiogenic growth factor (i.e., angiogenin) for endothelial cells, and thus promote angiogenesis to nurture the tumor microenvironment .…”

“…10 Preclinical studies have demonstrated that copper supplementation in rodent models significantly enhanced mammary, pancreatic, and lung cancer growth. [39][40][41] In addition, copper can regulate the expression and secretion of angiogenic molecules (e.g., vascular endothelial growth factor [VEGF], interleukin-1alpha [IL-1α], and fibroblast growth factors [FGFs]), and enhance the affinity of angiogenic growth factor (i.e., angiogenin) for endothelial cells, and thus promote angiogenesis to nurture the tumor microenvironment. 10,42 Further evidence indicates that copper may directly affect the ability of cancer cells to invade and metastasize through influencing the activities of copper-dependent proteins, such as lysyl oxydase (LOX), lysyl oxydase-like (LOXL) proteins and Memo.…”

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

“…In contrast, supplementation of water of pseudopregnant mice with CuSO 4 (198 mg/L) did not show any effect on the incidence of carcinogen-induced lymphomas, lung, ovaries, and breast cancers, which was most probably related to insufficient Cu concentrations in tissues (were not measured) [ 70 ]. Moreover, several studies demonstrated that supplementation of food and water with Cu salts has stimulated tumor progression [ 57 , 71 , 72 , 73 ]. When rats were given food with CuSO 4 (42.6 mg Cu/kg food) with or without antioxidant resveratrol, the carcinogen-induced mammary carcinogenesis was markedly accelerated [ 71 , 72 ].…”

“…Moreover, several studies demonstrated that supplementation of food and water with Cu salts has stimulated tumor progression [ 57 , 71 , 72 , 73 ]. When rats were given food with CuSO 4 (42.6 mg Cu/kg food) with or without antioxidant resveratrol, the carcinogen-induced mammary carcinogenesis was markedly accelerated [ 71 , 72 ]. This process was accompanied by the significant increase of serum Cu and decrease of serum Fe and Zn/Cu ratio similar to those observed in breast cancer patients [ 74 , 75 ].…”

Evaluation of protective effect of myricetin, a bioflavonoid in dimethyl benzanthracene-induced breast cancer in female Wistar rats

“…Myricetin proved the capacity of flavonols to act as antioxidant in cells definitely represents a potential in the field of oncology. [ 23 24 25 26 27 ]…”