Editing Arsenic poisoning (section)

===Oxidative stress===
Studies have demonstrated that the oxidative stress generated by arsenic may disrupt the signal transduction pathways of the nuclear transcriptional factors PPARs, AP-1, and NF-κB,<ref name = Vigo/><ref name=hu2002>{{cite journal|vauthors=Hu Y, Jin X, Snow ET |title=Effect of arsenic on transcription factor AP-1 and NF-κB DNA binding activity and related gene expression |journal=Toxicology Letters |volume=133 |issue=1 |pages=33–45 |date=July 2002 |pmid=12076508 |doi=10.1016/S0378-4274(02)00083-8|url=https://figshare.com/articles/journal_contribution/22858700 }}</ref><ref name = walton>{{cite journal|vauthors=Walton FS, Harmon AW, Paul DS, Drobná Z, Patel YM, Styblo M |title=Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes |journal=Toxicology and Applied Pharmacology |volume=198 |issue=3 |pages=424–33 |date=August 2004 |pmid=15276423 |doi=10.1016/j.taap.2003.10.026|bibcode=2004ToxAP.198..424W }}</ref> as well as the pro-inflammatory cytokines IL-8 and TNF-α.<ref name="Vigo"/><ref name=hu2002/><ref name = walton/><ref name = black>{{cite journal|author=Black PH |title=The inflammatory response is an integral part of the stress response: Implications for atherosclerosis, insulin resistance, type&nbsp;II diabetes and metabolic syndrome X |journal=Brain, Behavior, and Immunity |volume=17 |issue=5 |pages=350–64 |date=October 2003 |pmid=12946657 |doi=10.1016/S0889-1591(03)00048-5|s2cid=39222261 }}</ref><ref>{{cite journal|vauthors=Carey AL, Lamont B, Andrikopoulos S, Koukoulas I, Proietto J, Febbraio MA |title=Interleukin-6 gene expression is increased in insulin-resistant rat skeletal muscle following insulin stimulation |journal=Biochemical and Biophysical Research Communications |volume=302 |issue=4 |pages=837–40 |date=March 2003 |pmid=12646246 |doi=10.1016/S0006-291X(03)00267-5}}</ref><ref>{{cite journal|vauthors=Dandona P, Aljada A, Bandyopadhyay A |title=Inflammation: the link between insulin resistance, obesity and diabetes |journal=Trends in Immunology |volume=25 |issue=1 |pages=4–7 |date=January 2004 |pmid=14698276 |doi=10.1016/j.it.2003.10.013}}</ref><ref>{{cite journal|vauthors=Fischer CP, Perstrup LB, Berntsen A, Eskildsen P, Pedersen BK |title=Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans |journal=Clinical Immunology |volume=117 |issue=2 |pages=152–60 |date=November 2005 |pmid=16112617 |doi=10.1016/j.clim.2005.07.008}}</ref><ref>{{cite journal|vauthors=Gentry PR, Covington TR, Mann S, Shipp AM, Yager JW, Clewell HJ |title=Physiologically based pharmacokinetic modeling of arsenic in the mouse |journal=Journal of Toxicology and Environmental Health, Part A |volume=67 |issue=1 |pages=43–71 |date=January 2004 |pmid=14668111 |doi=10.1080/15287390490253660|bibcode=2004JTEHA..67...43G |s2cid=12481907 }}</ref> <!-- Table 1 (which will be posted later because it is still under construction) summarizes a number of rodent hepatic genes with differential expression associated with arsenic. These genes have been grouped according to functions such as oxidative stress, signal transduction, inflammation, and growth factor/hormone receptors.<ref>{{cite journal |vauthors=Chen H, Liu J, Merrick BA, Waalkes MP |title=Genetic events associated with arsenic-induced malignant transformation: applications of cDNA microarray technology |journal=Molecular Carcinogenesis |volume=30 |issue=2 |pages=79–87 |date=February 2001 |pmid=11241755 |doi=10.1002/1098-2744(200102)30:2<79::AID-MC1016>3.0.CO;2-F}}</ref> --> The interference of oxidative stress with signal transduction pathways may affect physiological processes associated with cell growth, metabolic syndrome X, glucose homeostasis, lipid metabolism, obesity, [[insulin resistance]], inflammation, and diabetes-2.<ref name = kota>{{cite journal|vauthors=Kota BP, Huang TH, Roufogalis BD |title=An overview on biological mechanisms of PPARs |journal=Pharmacological Research |volume=51 |issue=2 |pages=85–94 |date=February 2005 |pmid=15629253 |doi=10.1016/j.phrs.2004.07.012}}</ref><ref>{{cite journal|last1=Luquet|first1=Serge|last2=Gaudel|first2=Celine|last3=Holst|first3=Dorte|last4=Lopez-Soriano|first4=Joaquin|last5=Jehl-Pietri|first5=Chantal|last6=Fredenrich|first6=Alexandre|last7=Grimaldi|first7=Paul A.|title=Roles of PPAR delta in lipid absorption and metabolism: a new target for the treatment of type 2 diabetes|journal=Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease|date=May 2005|volume=1740|issue=2|pages=313–317|doi=10.1016/j.bbadis.2004.11.011|pmid=15949697|doi-access=free}}</ref><ref name = moraes>{{cite journal|vauthors=Moraes LA, Piqueras L, Bishop-Bailey D |title=Peroxisome proliferator-activated receptors and inflammation |journal=Pharmacology & Therapeutics |volume=110 |issue=3 |pages=371–85 |date=June 2006 |pmid=16168490 |doi=10.1016/j.pharmthera.2005.08.007}}</ref> Recent scientific evidence has elucidated the physiological roles of the PPARs in the ω- hydroxylation of fatty acids and the inhibition of pro-inflammatory transcription factors (NF-κB and AP-1), pro-inflammatory cytokines (IL-1, −6, −8, −12, and TNF-α), cell4 adhesion molecules (ICAM-1 and VCAM-1), inducible nitric oxide synthase, proinflammatory nitric oxide (NO), and anti-apoptotic factors.<ref name = Vigo/><ref name= black/><ref name = kota/><ref name = moraes/><ref>{{cite journal|vauthors=Hara K, Okada T, Tobe K |title=The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes |journal=Biochemical and Biophysical Research Communications |volume=271 |issue=1 |pages=212–6 |date=April 2000 |pmid=10777704 |doi=10.1006/bbrc.2000.2605|display-authors=etal}}</ref>

Epidemiological studies have suggested a correlation between chronic consumption of drinking water contaminated with arsenic and the incidence of type 2 diabetes.<ref name="Vigo"/> The human liver after exposure to therapeutic drugs may exhibit hepatic non-cirrhotic portal hypertension, fibrosis, and cirrhosis.<ref name="Vigo"/> However, the literature provides insufficient scientific evidence to show cause and effect between arsenic and the onset of diabetes mellitus Type 2.<ref name="Vigo"/>