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Effects of chronic arsenic oral exposure on hepatic and intestinal CYP expression
Author(s) -
Fan Xiaoyu,
Liu Pengfei,
Han Weiguo,
Wu Xiangmeng,
Ding Liang,
Zhang Donna,
Ding Xinxin,
Zhang QingYu
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.506.2
Subject(s) - xenobiotic , arsenic , sodium arsenite , physiology , ingestion , drug metabolism , pharmacology , biology , arsenite , toxicity , drug , chemistry , toxicology , enzyme , endocrinology , medicine , biochemistry , organic chemistry
Environmental exposure to arsenic is associated with increased incidences of multiple adverse health consequences in humans, posing a significant health risk to people living near contaminated sites. For example, populations residing near mining sites may be exposed to mine tailings through the inhalation of dust particles or ingestion of contaminated water or food, as the arsenic contaminants may become bio‐accessible. Previous studies in rodents reported the ability of short‐term exposures to arsenic at high doses to increase or decrease the expression of several xenobiotic metabolizing CYPs in liver, lung, heart, or kidney, raising the possibility that exposed human individuals may have altered ability to metabolize drugs and other xenobiotic compounds. The aim of this study is to examine effects of chronic arsenic oral exposure at a relatively low level on expression of various CYPs in the liver. In the first experiment, mice were fed control or sodium arsenite‐containing drinking water (25 ppm) for 20 weeks. Hepatic gene expression was analyzed using RNA‐seq, which revealed significant increases in transcript levels for several CYPs, including CYP2A5 (by 10‐fold), an enzyme known for its activities toward nicotine, various environmental toxicants, as well as endogenous compounds. In a follow‐up study, hepatic CYP2A5 transcript level, determined by real‐time PCR, was also found to be increased (by 2.5‐fold) after 4 weeks of exposure to arsenic. Induction of CYP2A protein was confirmed by immunoblot analysis of both sets of samples. Like CYP2A5, hepatic expression of CYP3A11, a major drug‐metabolizing CYP enzyme, was also induced by arsenic exposure for 4 or 20 weeks. CYP expression in the intestine was also examined in the 4‐week exposed groups. CYP3A11, but not CYP2A5, is expressed in the intestine. Induction of CYP3A11 expression was observed in the proximal but not distal intestine, and it was less than 2‐fold. Taken together, these data reveal significant induction of hepatic CYP2A5 and CYP3A11 expression by chronic exposure to a low dose of arsenic in drinking water. The impact of this model of arsenic exposure on hepatic and intestinal xenobiotic metabolism is currently under study. Support or Funding Information NIH grants ES020867 and GM082978 This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .