PMID- 30357758 OWN - NLM STAT- MEDLINE DCOM- 20200204 LR - 20200204 IS - 1559-0720 (Electronic) IS - 0163-4984 (Linking) VI - 190 IP - 2 DP - 2019 Aug TI - The Variable Regulatory Effect of Arsenic on Nrf2 Signaling Pathway in Mouse: a Systematic Review and Meta-analysis. PG - 362-383 LID - 10.1007/s12011-018-1549-x [doi] AB - Arsenic is known to cause oxidative damage. Nuclear factor E2-relate factor-2 (Nrf2) can resist this toxicity. Scholars demonstrated that Nrf2 pathway was activated by arsenic. In contrast, other articles established arsenic-induced inhibition of Nrf2 pathway. To resolve the contradiction and elucidate the mechanism of Nrf2 induced by arsenic, 39 publications involving mouse models were identified through exhaustive database retrieval and were analyzed. The pooled results suggested that arsenic obviously elevated transcription and translation levels of Nrf2 and its downstream genes, NAD(P)H dehydrogenase 1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and GST-glutathione-S-transferase1/2 (GSTO1/2). Arsenic increased the level of reactive oxygen species (ROS), but reduced the level of glutathione (GSH). Subgroup analysis between arsenic and control groups showed that the levels of Nrf2 and its downstream genes are greater in high dose than that in the low dose, higher in short-term exposure than long term, female subjects tolerated better than males, higher in mice than the rats, and greater in other organs than the liver. However, the contents of genes of Nrf2 pathway between the arsenic and control groups were lower in rats than in mice and were less for long-term exposure than the short term (P < 0.05). Conclusively, a variable regulation of arsenic on Nrf2 pathway is noted. Higher dose and short-term exposure of female mice organs except for liver promoted Nrf2 pathway. On the other hand, arsenic inhibited Nrf2 pathway for long-term exposure on rats. FAU - Wang, Cheng AU - Wang C AUID- ORCID: 0000-0002-7727-0565 AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Niu, Qiang AU - Niu Q AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Ma, Rulin AU - Ma R AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Song, Guanling AU - Song G AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Hu, Yunhua AU - Hu Y AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Xu, Shangzhi AU - Xu S AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Li, Yu AU - Li Y AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Wang, Haixia AU - Wang H AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. FAU - Li, Shugang AU - Li S AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. lishugang@ymail.com. FAU - Ding, Yusong AU - Ding Y AD - Department of Public Health and Key Laboratory of Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, Shihezi, 832002, Xinjiang, China. 13399931625@163.com. LA - eng GR - 81560517/the National Natural Science Foundation of China/ GR - 81760584/the National Natural Science Foundation of China/ GR - 2014BA039/the Key Areas of Science and Technology Research Project of Xinjiang Production and Construction Corps/ GR - 2015AG014/the Key Areas of Science and Technology Research Project of Xinjiang Production and Construction Corps/ GR - RCZX201112/the High-tech Intellectual Project of Shihezi University/ GR - GJHZ201602/the International Cooperative Project of Shihezi University/ PT - Journal Article PT - Meta-Analysis PT - Systematic Review DEP - 20181025 PL - United States TA - Biol Trace Elem Res JT - Biological trace element research JID - 7911509 RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - N712M78A8G (Arsenic) SB - IM MH - Animals MH - Arsenic/*toxicity MH - Mice MH - NF-E2-Related Factor 2/*metabolism MH - Signal Transduction/*drug effects MH - Structure-Activity Relationship OTO - NOTNLM OT - Arsenic OT - Meta-analysis OT - Nrf2 signaling pathway OT - Systematic review EDAT- 2018/10/26 06:00 MHDA- 2020/02/06 06:00 CRDT- 2018/10/26 06:00 PHST- 2018/06/22 00:00 [received] PHST- 2018/10/11 00:00 [accepted] PHST- 2018/10/26 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] PHST- 2018/10/26 06:00 [entrez] AID - 10.1007/s12011-018-1549-x [pii] AID - 10.1007/s12011-018-1549-x [doi] PST - ppublish SO - Biol Trace Elem Res. 2019 Aug;190(2):362-383. doi: 10.1007/s12011-018-1549-x. Epub 2018 Oct 25.