Graduate Program in Biological Sciences, Toxicological Biochemistry, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Graduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
Food Chem Toxicol. 2018 Nov;121:519-526. doi: 10.1016/j.fct.2018.09.038. Epub 2018 Sep 20.
There are some genes associated to the risk of chronic diseases that present potential nutrigenetic response, such as the human manganese-dependent superoxide dismutase gene (Val16Ala-SOD2, rs4880) for which homozygous genotypes (VV and AA) are associated with higher basal superoxide (S) and hydrogen peroxide (HP) levels, respectively. It is possible that the VV- and AA-imbalance could be attenuated by selenium(Se)-rich foods such as Brazil nut (BN). To test this hypothesis, we conducted an in vitro protocol triggering a chemical S-HP imbalance by exposure of dermal fibroblast cells (HFF-1) to paraquat, which generates high S levels (VV-like treatment) and porphyrin (MnTBAP), which generates high HP levels (AA-like treatment). Modulation of cell growth and pro-oxidative and antioxidant markers were evaluated. BN aqueous extract (BNAE) most effective concentration which increased cell growth and decreased oxidative metabolism indicators of imbalanced cells was 75 ng Se/mL. However, this effect was not directly affected by the S-HP imbalance: in AA-SOD2-like cells, thioredoxin reductase (TrxR-1) gene was upregulated and in VV-SOD2-like cells an upregulation of glutathione peroxidase (GPx-1) gene expression was observed, however, this regulation occured in a homeostatic manner. These results suggest that BNAE was able to minimize negative effects in both directions of the S-HP imbalance, by modulation of different oxidative-metabolic pathways.
有一些与慢性病风险相关的基因表现出潜在的营养遗传学反应,例如人类锰依赖性超氧化物歧化酶基因(Val16Ala-SOD2,rs4880),其纯合基因型(VV 和 AA)分别与较高的基础超氧化物(S)和过氧化氢(HP)水平相关。富含硒(Se)的食物,如巴西坚果(BN),可能会减轻 VV 和 AA 失衡。为了验证这一假设,我们进行了一项体外方案,通过将皮肤成纤维细胞(HFF-1)暴露于百草枯来引发 S-HP 失衡,百草枯会产生高水平的 S(类似于 VV 的处理)和卟啉(MnTBAP),会产生高水平的 HP(类似于 AA 的处理)。评估了细胞生长和促氧化和抗氧化标志物的变化。增加细胞生长并降低失衡细胞氧化代谢指标的 BN 水提物(BNAE)最有效浓度为 75ng Se/mL。然而,这种效果并不是直接受到 S-HP 失衡的影响:在 AA-SOD2 样细胞中,硫氧还蛋白还原酶(TrxR-1)基因上调,而在 VV-SOD2 样细胞中,谷胱甘肽过氧化物酶(GPx-1)基因表达上调,但这种调节是在一种稳态方式下发生的。这些结果表明,BNAE 能够通过调节不同的氧化代谢途径,最大限度地减少 S-HP 失衡的两个方向的负面影响。