The Effects of Formaldehyde on Cytochrome P450 Isoform Activity in Rats. (7th May 2017)

• Record Type: Journal Article
• Authors: Xu, Min; Tang, Huaqiao; Rong, Qian; Zhang, Yuanli; Li, Yinglun; Zhao, Ling; Ye, Gang; Shi, Fei; Lv, Cheng
• Other Names: Laffon Blanca Academic Editor.
• Is Part Of: BioMed research international. Volume 2017(2017)
• Publication Date: 2017-05-07
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2017/6525474
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t 1 / 2, A U C ( 0 - t ), and C m a x of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P < 0.05 ), whereas the CL of chlorzoxazone and testosterone decreased significantly (P < 0.05 ). However, t 1 / 2, A U C ( 0 - t ), and C m a x of phenacetin decreased significantly (P < 0.05 ), whereas the CL of phenacetin increased significantly (P < 0.05 ) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.