Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis

Romualdo, Guilherme Ribeiro; Goto, Renata L.; Fernandes, Ana Angélica Henrique; Cogliati, Bruno; Barbisan, Luı́s Fernando

doi:10.1016/j.fct.2016.08.020

Cited by 15 publications

(11 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here we show in the zebrafish embryo that zinc deficiency was associated with the suppression of several genes that respond to oxidative stress ( nrf2a , nrf2b , mt2 , and ogg1 ) at the mRNA level. Suppression of nrf2 with zinc deficiency has been observed in the past and has been associated with oxidative stress [71–73]. In contrast, Ogg1 protein has been shown to be induced with zinc deficiency in adult rat livers [42].…”

Section: Discussionmentioning

confidence: 99%

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

et al. 2017

View full text Add to dashboard Cite

Zinc deficiency and chronic low level exposures to inorganic arsenic in drinking water are both significant public health concerns that affect millions of people including pregnant women. These two conditions can co-exist in the human population but little is known about their interaction, and in particular, whether zinc deficiency sensitizes individuals to arsenic exposure and toxicity, especially during critical windows of development. To address this, we utilized the Danio rerio (zebrafish) model to test the hypothesis that parental zinc deficiency sensitizes the developing embryo to low-concentration arsenic toxicity, leading to altered developmental outcomes. Adult zebrafish were fed defined zinc deficient and zinc adequate diets and were spawned resulting in zinc adequate and zinc deficient embryos. The embryos were treated with environmentally relevant concentrations of 0, 50, and 500 ppb arsenic. Arsenic exposure significantly reduced the amount of zinc in the developing embryo by ~7%. The combination of zinc deficiency and low-level arsenic exposures did not sensitize the developing embryo to increased developmental malformations or mortality. The combination did cause a 40% decline in physical activity of the embryos, and this decline was significantly greater than what was observed with zinc deficiency or arsenic exposure alone. Significant changes in RNA expression of genes that regulate zinc homeostasis, response to oxidative stress and insulin production (including zip1, znt7, nrf2, ogg1, pax4, and insa) were found in zinc deficient, or zinc deficiency and arsenic exposed embryos. Overall, the data suggests that the combination of zinc deficiency and arsenic exposure has harmful effects on the developing embryo and may increase the risk for developing chronic diseases like diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

et al. 2017

View full text Add to dashboard Cite

show abstract

“…in 0.9% saline, Sigma-Aldrich, USA] or saline vehicle at postnatal day (PND) 15 ( Fig. 1) (Romualdo et al, 2016). From PND 40 onwards, the female mice were allocated into four groups receiving different experimental diets: standard diet (untreated group) (n ¼ 5 mice); standard diet containing 0.02% HCB (w/w, DEN/HCB group) (n ¼ 10 mice) (British Drug House Chemicals, UK); standard diet containing 0.02% HCB and supplementation with 10,000 or 20,000 IU of VD 3 (BASF, Germany) per Kg of chow, respectively (VD 3 10,000 and VD 3 20,000 groups) (n ¼ 10 mice, both) during 20 weeks.…”

Section: Experimental Designmentioning

confidence: 99%

“…For these reasons, HCB is usually used as a classical promoting agent in chemically-induced rodent models of hepatocarcinogenesis (Gustafson et al, 2000;Portaz et al, 2015). In these models, the altered hepatocyte foci (AHF), considered as hepatocellular PNL, are easily identified and quantified in short and medium-term bioassays, allowing the investigation of potential modifying factors on early stage of hepatocarcinogenesis, including dietary micronutrients (Klaunig and Kamendulis, 1999;Ogawa, 2009;Romualdo et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D3 supplementation attenuates the early stage of mouse hepatocarcinogenesis promoted by hexachlorobenzene fungicide

Romualdo

Goto

Fernandes

et al. 2017

Food and Chemical Toxicology

Self Cite

View full text Add to dashboard Cite

Hexachlorobezene (HCB), a fungicide widely distributed in the environment, promotes the development of hepatocellular preneoplastic lesions (PNL) and tumors in rodents. In contrast, vitamin D (VD) supplementation presents a potential role for the prevention/treatment of chronic liver diseases. Thus, we investigated whether VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis. Female Balb/C mice were injected a single dose of diethylnitrosamine (DEN, 50 mg/kg) at postnatal day 15. From day 40 onwards, mice were fed with a standard diet containing 0.02% HCB alone or supplemented with VD (10,000 or 20,000 IU/Kg diet) for 20 weeks. Untreated mice were fed just standard diet. After this period, mice were euthanized and liver and serum samples were collected. Compared to the untreated group, DEN/HCB treatment decreased total hepatic glutathione levels and glutathione peroxidase (GSH-Px) activity while increased lipid peroxidation, p65 protein expression, cell proliferation/apoptosis and the PNL development. In contrast, dietary VD supplementation enhanced vitamin D receptor (VDR) protein expression, total glutathione levels and GSH-Px activity while diminished lipid hydroperoxide levels. Also, VD supplementation decreased p65 protein expression, hepatocyte proliferation, the size and the liver area occupied by PNL. Therefore, our findings indicate that VD supplementation attenuates the early stage of HCB-promoted hepatocarcinogenesis.

show abstract

“…7,12-Dimethylbenzantracene (DMBA) was purchased from Sigma Chemical Co. (CAS 57-97-6,~95%: -St. Louis, MO, USA). The semipurified diets (AIN-93G) were obtained from HN&C -Consulting in Experimental Nutrition (Campinas-SP, Brazil) with different zinc levels (zinc sulfate): zinc-adequate diet (ZnA, 35-mg/kg chow); zincdeficient diet (ZnD, 3-mg/kg chow) and zinc-supplemented diet (ZnS180-mg/kg chow) [24]. Samples of each AIN-93G diet formulation (in triplicate) were submitted to flameless atomic absorption spectroscopy (AAS) analysis, confirming zinc levels in the experimental diets before introducing them to the dams [24].…”

Section: Chemical and Dietsmentioning

confidence: 99%

“…Immediately before euthanasia at PND 51, blood samples were collected by cardiac puncture to further determine serum zinc levels. Serum samples were mineralized in a 16-N nitric acid solution by microwave irradiation, and zinc level was determined from the mineralized materials by flameless AAS (GBC, Model 932 AA) [24].…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats

Silva

Grassi

Zapaterini

et al. 2017

The Journal of Nutritional Biochemistry

View full text Add to dashboard Cite

Zinc deficiency during pregnancy and postnatal life can adversely increase risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes in the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant female SD rats were allocated into three groups: zinc-adequate diet (ZnA - 35-mg/kg chow), zinc-deficient diet (ZnD - 3-mg/kg chow) or zinc-supplemented diet (ZnS - 180-mg/kg chow) during gestational day 10 (GD 10) until the litters' weaning. Female offspring received the same diets as their dams until postnatal day (PND) 51. At PND 51, the animals received a single dose of DMBA (50 mg/kg, ig) and zinc-adequate diets. At PND 180, female were euthanized, and tumor samples were processed for histological evaluation and gene expression microarray analysis. The ZnD induced a significant reduction in female offspring body weight evolution and in mammary gland development. At late in life, the ZnD or ZnS did not alter the latency, incidence, multiplicity, volume or histological types of mammary tumors in relation to the ZnA group. However, the total tumor number in ZnS group was higher than in ZnA group, accompanied by distinct expression of 4 genes up- and 15 genes down-regulated. The present findings indicate that early-in-life dietary zinc supplementation, differently to zinc deficiency, has a potential to modify the susceptibility to the development of mammary tumors induced by DMBA.

show abstract

Dietary zinc deficiency predisposes mice to the development of preneoplastic lesions in chemically-induced hepatocarcinogenesis

Cited by 15 publications

References 73 publications

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

Combinatorial effects of zinc deficiency and arsenic exposure on zebrafish (Danio rerio) development

Vitamin D3 supplementation attenuates the early stage of mouse hepatocarcinogenesis promoted by hexachlorobenzene fungicide

Early-in-life dietary zinc deficiency and supplementation and mammary tumor development in adulthood female rats

Contact Info

Product

Resources

About