Effect of styrene oxide and diethyl maleate on expression of cytochrome P450 family 1 and glutathione store in mouse liver

Abstract


 
 
 
 Purpose: To determine the effect of the glutathione (GSH) suppressors styrene oxide (SO) and diethyl maleate (DEM) on the hepatic expression of cytochrome P450 family 1 (Cyp1) isoforms that are related to carcinogenesis including Cyp1a1, Cyp1a2, and Cyp1b1.
 Methods: Seven-week-old ICR mice were intraperitoneally injected with SO (150 and 300 mg/kg/day), DEM (175 and 350 mg/kg/day), or N-acetylcysteine (NAC; 300 and 600 mg/kg/day) for 7, 14, or 28 days. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic Cyp1 expression, total glutathione, reduced glutathione (GSH), and oxidized glutathione (GSSG) were determined.
 Results: ALT and AST levels were markedly increased by SO and DEM while GSH/GSSG ratio was decreased by SO in all treatments (p < 0.05), while high dose (350 mg/kg/day) DEM significantly suppressed GSH/GSSG ratio at 28 days (p < 0.05). The expressions of Cyp1a1, Cyp1a2, and Cyp1b1 were induced by SO and DEM, corresponding with induction of ethoxy/methoxy-resorufin O- dealkylase activities.
 Conclusion: The Cyp1 family metabolizes procarcinogens to carcinogenic DNA adducts; exposure to the industrial solvents, SO and DEM, raises the risk of carcinogenesis via GSH depletion coupled with Cyp1 induction.
 
 
 

Early enteric and hepatic responses to ingestion of polystyrene nanospheres from water in C57BL/6 mice

“…Interestingly, size-specific PSNS exposure induced a trend toward differences in liver cyp1b1 gene expression, which encodes a phase I detoxification enzyme (reviewed in Hodges and Minich, 2015). Although this effect was not significant, yet had an effect size of 1.524351 based on Cohen's d, it aligns with findings from other studies assessing the impact of styrene oxide or microplastic exposure on vertebrates where cyp1b1 or cyp1a were differentially expressed in the liver (Granby et al, 2018;Chatuphonprasert and Jarukamjorn, 2021). Accordingly, we hypothesize that ingestion of PSNS activates phase I metabolism pathways.…”

Pneumotoxicity of Styrene Oxide and the Possible Protective Role of Thymosin β4 in Albino Rat: Biochemical and Immunohistochemical Study

“…H&E stained sections of SO group showed; multiple collapsed alveoli, infiltration by inflammatory cells, dilated congested blood vessels, interstitial hemorrhage, and edema, this was consistent with the study of Arab et al [7]. The lung tissue injuries may be due to low lung levels of the main antioxidant GSH [4] that also increased the risk of tumor development in experimental animals [56], and caused cell damage and lysis in different organs [25].…”

“…Styrene oxide (SO) (Sigma-Aldrich, Steinheim, Germany) was soluble in sterile water with a purity of 97% injected intraperitoneally (i.p.) at a daily dose of 300 mg/kg for 28 days [25]. Thymosin β4 (Tβ4) in a form of Thymosin Beta 500 (TB-500) 10 mg vial (Peptides, SKU: 0013-2) was injected i.p.…”

“…Tβ4 group: rats were injected i.p with 1mg/kg of Tβ4 [20], once daily for 28 days. SO group: rats were injected i.p with 300 mg/kg of SO, once daily for 28 days [25]. SO+ Tβ4 group: rats were concomittently injected i.p with 300 mg/kg of SO and 1mg/kg of Tβ4, once daily for 28 days.…”