Abstract

Fluoride is the most common cause of drinking water-associated toxicity and is known to induce various metabolic imbalances and dental/skeletal fluorosis. The present study analyzed the protective effect of Borassus flabellifer Linn. haustorium extract (BHE) against fluoride-induced intestinal redox metabolism and apoptosis. The total polyphenols and total flavonoids present in BHE were estimated to be 39.67 ± 5.14 mg gallic acid equivalent/g extract and 8.59 ± 0.74 mg quercetin equivalent. In cultured intestinal epithelial cells (IEC-6), sodium fluoride exposure-induced apoptosis mediated through antioxidant enzyme inhibition and subsequent oxidative damages. Further, there observed an increased expression of caspase-3, caspase-7, and apoptotic protease activating factor-1 (apaf-1) genes, increased cytochrome C release, and caspase 3/7 activity indicating the apoptosis- mediated cell death (p < 0.05). Upon pretreatment with BHE, the cytotoxic effect of fluoride was reduced by decreasing the expression of apoptotic genes and increased the cytochrome release as well as caspase 3/7 activity (p < 0.01). Providing the mechanistic basis, the expression of nuclear factor erythroid 2-related factor-2 (Nrf2)/haeme oxygenase-1 (HO1) gene was increased in the BHE pretreated cells; corroborating to these, there observed increased activity of glutathione biosynthetic enzymes (p < 0.05) and glutathione reductase. Hence, the protective effect of BHE may be mediated through Nrf2-mediated glutathione biosynthesis, the subsequent establishment of redox balance, and inhibition of apoptosis in intestinal epithelial cells.

摘要

氟化物是饮用水相关毒性的最常见原因，已知会导致各种代谢失衡和氟牙症/氟骨症。本研究分析了Borassus flabellifer的保护作用林恩。吸器提取物（BHE）对抗氟化物诱导的肠道氧化还原代谢和细胞凋亡。BHE 中的总多酚和总黄酮估计为 39.67 ± 5.14 mg 没食子酸当量/g 提取物和 8.59 ± 0.74 mg 槲皮素当量。在培养的肠上皮细胞 (IEC-6) 中，氟化钠暴露通过抗氧化酶抑制和随后的氧化损伤介导诱导细胞凋亡。此外，观察到 caspase-3、caspase-7 和凋亡蛋白酶激活因子-1 (apaf-1) 基因的表达增加，细胞色素 C 释放增加和 caspase 3/7 活性表明细胞凋亡介导的细胞死亡（p < 0.05)。经 BHE 预处理后，氟化物的细胞毒作用通过降低凋亡基因的表达而降低，并增加了细胞色素的释放以及 caspase 3/7 的活性（p  < 0.01）。提供机制基础，BHE预处理细胞中核因子红细胞2相关因子2（Nrf2）/血红素加氧酶1（HO1）基因的表达增加；证实了这些，观察到谷胱甘肽生物合成酶（p  < 0.05）和谷胱甘肽还原酶的活性增加。因此，BHE 的保护作用可能是通过 Nrf2 介导的谷胱甘肽生物合成、随后建立氧化还原平衡和抑制肠上皮细胞凋亡来介导的。