性别差异在砷的生物转化中是砷毒性的一个重要代谢基础。
Gender difference in arsenic biotransformation is an important metabolic basis for arsenic toxicity.
机构信息
Department of Occupational Health and Environmental Health, Public Health College of Xinjiang Medical University, No.567, Sunde North Road, Shuimogou District, Xinjiang, 830011, Urumqi, People's Republic of China.
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, 830011, Urumqi, People's Republic of China.
出版信息
BMC Pharmacol Toxicol. 2022 Feb 28;23(1):15. doi: 10.1186/s40360-022-00554-w.
BACKGROUND
Arsenic metabolism enzymes can affect the toxic effects of arsenic. However, the effects of different genders on the metabolites and metabolic enzymes in liver arsenic metabolism is still unclear. This study analyzed the gender differences of various arsenic metabolites and metabolic enzymes and further explored the effects of gender differences on arsenic metabolism in liver tissues of rats.
METHODS
Rats were treated with high/medium/low doses of iAs or iAs. Liver pathological changes were observed with electron microscopy. The monomethyl aracid (MMA) and dimethyl aracid (DMA) was determined by high performance liquid chromatography-hydride generation atomic fluorescence spectroscopy. S-adenosylmethionine (SAM), arsenate respiratory reductase (ARR), nicotinamide adenine dinucleotide (NAD), purine nucleoside phosphorylase (PNP), pyruvate kinase (PK), and myeloperoxidase (MPO) SAM, ARR, NAD, PNP, PK, and MPO were determined by enzyme-linked immunoassay. RT-qPCR was used to determine Arsenic (+ 3 oxidation state) methyltransferase (AS3MT).
RESULTS
The iAs and iAs at high doses induced pathological changes in the liver, such as increased heterochromatin and lipid droplets. Compared within the same group, MMA and DMA were statistically significant in iAs high, iAs medium and iAs low dose groups (P < 0.05). MMA of male rats in iAs high and medium groups was higher than that of female rats, and the DMA of male rats was lower than that of female rats. As3MT mRNA in the male iAs high group was higher than that of females. Besides, compared between male and female, only in iAS low dose, iAS medium dose, iAS low dose, and iAS medium dose groups, there was significant difference in SAM level (P < 0.05). Compared within the same group, male rats had significantly higher PNP and ARR activities while lower PK activity than female rats (P < 0.05). Between the male and female groups, only the iAS high dose and medium dose group had a statistically significant difference (P < 0.05). The NAD activity of females in iAS high dose group was higher than that of males.
CONCLUSION
The gender differences in the arsenic metabolism enzymes may affect the biotransformation of arsenic, which may be one of the important mechanisms of arsenic toxicity of different sexes and different target organs.
背景
砷代谢酶可影响砷的毒性作用。然而，不同性别对肝脏砷代谢中代谢物和代谢酶的影响尚不清楚。本研究分析了不同砷代谢物和代谢酶的性别差异，并进一步探讨了性别差异对大鼠肝脏组织砷代谢的影响。
方法
用高/中/低剂量的 iAs 或 iAs 处理大鼠。用电子显微镜观察肝组织的病理变化。采用高效液相色谱-氢化物发生原子荧光光谱法测定一甲基砷酸（MMA）和二甲基砷酸（DMA）。用酶联免疫吸附法测定 S-腺苷甲硫氨酸（SAM）、砷酸盐呼吸还原酶（ARR）、烟酰胺腺嘌呤二核苷酸（NAD）、嘌呤核苷磷酸化酶（PNP）、丙酮酸激酶（PK）和髓过氧化物酶（MPO）。采用 RT-qPCR 法测定砷（+3 氧化态）甲基转移酶（AS3MT）。
结果
高剂量的 iAs 和 iAs 诱导肝脏发生病理变化，如异染色质增加和脂滴增多。同一组内比较，iAs 高、中、低剂量组的 MMA 和 DMA 均有统计学差异（P<0.05）。iAs 高、中剂量组雄性大鼠的 MMA 高于雌性大鼠，而 DMA 低于雌性大鼠。iAs 高剂量组雄性大鼠的 As3MT mRNA 高于雌性大鼠。此外，与雌雄大鼠比较，仅在 iAs 低、中、低、中剂量组，SAM 水平有显著差异（P<0.05）。同一组内比较，雄性大鼠的 PNP 和 ARR 活性显著高于雌性大鼠，PK 活性显著低于雌性大鼠（P<0.05）。雌雄大鼠比较，仅 iAs 高、中剂量组有统计学差异（P<0.05）。iAs 高剂量组雌性大鼠的 NAD 活性高于雄性大鼠。
结论
砷代谢酶的性别差异可能影响砷的生物转化，这可能是砷毒性不同性别和不同靶器官的重要机制之一。
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