Depletion by Styrene of Glutathione in Plasma and Bronchioalveolar Lavage Fluid of Non-Swiss Albino (NSA) Mice

Carlson, Gary P.

doi:10.1080/15287391003689143

Cited by 8 publications

(10 citation statements)

References 35 publications

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“…Therefore, its loss due to oxidative stress or conjugation with styrene suggests adverse ramifications on cells like induction of apoptosis. One more study supported this claim where styrene (600 mg/kg) and its metabolites (300 mg/kg) significantly reduced GSH levels in broncho‐alveolar lavage (BAL) fluid and plasma . El‐Ziney et al used TBARS assay and showed very low doses of styrene (monostyrene) could increase LPO in female rats more than males.…”

Section: Discussionmentioning

confidence: 93%

“…One more study supported this claim where styrene (600 mg/kg) and its metabolites (300 mg/kg) significantly reduced GSH levels in broncho-alveolar lavage (BAL) fluid and plasma. 43 El-Ziney et al 44 used TBARS assay and showed very low doses of styrene (monostyrene) could increase LPO in female rats more than males. This may be due to the high conversion of this compound to its oxide forms in females rather than males.…”

Section: Discussionmentioning

confidence: 99%

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Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Niaz

Mabqool

Khan

et al. 2017

Environmental Toxicology

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Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue. For this purpose, styrene was dissolved in corn oil and was administered via gavage, at doses 250, 500, 1000, 1500, 2000, mg/kg/day per mL and control (corn oil) to each rat with one day off in a week, for 42 days. Plasma SOD and protein carbonyl of plasma were significantly up-regulated in 1000, 1500, and 2000 mg/kg/day styrene administrated groups (P < .001). In addition, styrene caused an increase in lipid peroxidation (LPO) and reactive oxygen species (ROS) in the dose-dependent manners in liver tissue (P < .001). Furthermore, the ferrous reducing antioxidant power (FRAP) and total thiol molecules (TTM) in styrene-treated groups were significantly decreased in liver tissue (P < .001) with increasing doses. In treated rats, styrene significantly increased G6Pase activity (P < .001) and down-regulated GP activity (P < .001) as compared to the control group. The PEPCK activity was significantly raised in a dose-dependent manner (P < .001). The ATP/ADP ratio of live cells was significantly raised by increasing the dose (P < .001). There was significantly an up-regulation of GLUD1 and GCK at 2000 mg/kg group (P < .01) and a down-regulation for GLUT2 at the same dose. While in the rest of group, GLUT2 showed up-regulation of relative fold change. By targeting genes such as GLUD1, GLUT2, and GCK, disruption of hepatic gluconeogenesis, glycogenolysis, and insulin secretory functions are obvious. The present study illustrates that induction of oxidative stress followed by changes in G6Pase, GP, and PEPCK activities and the genes responsible for glucose metabolism are the mechanisms of styrene's action in the liver.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Niaz

Mabqool

Khan

et al. 2017

Environmental Toxicology

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“…These doses have been used in previous studies by us (Gadberry et al, 1996;Carlson, 1997Carlson, , 2010Carlson et al, 2006;Harvilchuck et al, 2008Harvilchuck et al, , 2009Meszka-Jordan et al, 2009). However, toxicity required lowering of these doses to 200 and 150 mg/kg respectively.…”

Section: Experimental Designmentioning

confidence: 95%

“…In a second pathway, styrene oxide is conjugated with glutathione (GSH). The mechanism of styrene-induced toxicity is not completely clear but may be related to oxidative stress (Harvilchuck et al, 2008(Harvilchuck et al, , 2009Meszka-Jordan et al, 2009), since styrene produces significant decreases in GSH levels in liver and lung as well as in plasma and bronchioalveolar lavage fluid (Carlson, 2010). This may in part be related to the conjugation of styrene oxide with GSH.…”

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confidence: 98%

Metabolism and Toxicity of Styrene in Microsomal Epoxide Hydrolase-Deficient Mice

Carlson

2010

Journal of Toxicology and Environmental Health, Part A

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Styrene, which is widely used in manufacturing, is both acutely and chronically toxic to mice. Styrene is metabolized by cytochromes P-450 to the toxic metabolite styrene oxide, which is detoxified via hydrolysis with microsomal epoxide hydrolase (mEH) playing a major role. The purpose of these studies was to characterize the importance of this pathway by determining the hepatotoxicity and pneumotoxicity of styrene in wild-type and mEH-deficient (mEH(-/-)) mice. While the mEH(-/-) mice metabolized styrene to styrene oxide at the same rate as the wild-type mice, as expected there was minimal metabolism of styrene oxide to glycol. mEH(-/-) mice were more susceptible to the lethal effects of styrene. Twenty-four hours following the administration of 200 mg/kg ip styrene, mice demonstrated a greater hepatotoxic response due to styrene, as measured by increased serum sorbitol dehydrogenase activity and greater pneumotoxicity as shown by increased protein levels, cell numbers, and lactate dehydrogenase activity in bronchioalveolar lavage fluid. mEH(-/-) mice were also more susceptible to styrene-induced oxidative stress, as indicated by greater decreases in hepatic glutathione levels 3 h after styrene. Styrene oxide at a dose of 150 mg/kg did not produce hepatotoxicity in either wild-type or mEH(-/-) mice. However, styrene oxide produced pneumotoxicity that was similar in the two strains. Thus, mEH plays an important role in the detoxification of styrene but not for exogenously administered styrene oxide.

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“…Address correspondence to Gary P. Carlson (Carlson, 2010a). In a recent study, microsomal epoxide hydrolase (mEH -/-) knockout mice were found to be more susceptible than wild-type mice to styrene-induced hepatotoxicity, pneumotoxicity, and oxidative stress (Carlson, 2010b).…”

mentioning

confidence: 98%

Comparison of Styrene Oxide Enantiomers for Hepatotoxic and Pneumotoxic Effects in Microsomal Epoxide Hydrolase-Deficient Mice

Carlson

2011

Journal of Toxicology and Environmental Health, Part A

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Styrene is hepatotoxic and pneumotoxic in mice. Styrene oxide, the active metabolite, is detoxified via hydrolysis by microsomal epoxide hydrolase (mEH). Racemic styrene oxide was previously found to be more lethal and produced increased toxicity in mEH-/- mice compared to wild-type mice. The hepatotoxicity and pneumotoxicity of the R- and S-styrene oxide (SO) enantiomers were compared in wild-type and mEH-deficient mice (mEH-/-). Twenty-four hours following administration of 150 mg/kg ip, neither enantiomer produced hepatotoxicity, but S-SO was more pneumotoxic. However, in mEH-/- mice R-SO produced greater decreases in hepatic glutathione levels 3 h after administration. The basis for the unusual greater toxicity of S-SO, rather than the generally more toxic R-SO, in mEH-/- mice may be related to differences in detoxification by EH.

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Depletion by Styrene of Glutathione in Plasma and Bronchioalveolar Lavage Fluid of Non-Swiss Albino (NSA) Mice

Cited by 8 publications

References 35 publications

Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Molecular mechanisms of action of styrene toxicity in blood plasma and liver

Metabolism and Toxicity of Styrene in Microsomal Epoxide Hydrolase-Deficient Mice

Comparison of Styrene Oxide Enantiomers for Hepatotoxic and Pneumotoxic Effects in Microsomal Epoxide Hydrolase-Deficient Mice

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