CC10 mRNA and protein expression in Clara cells of CD-1 mice following exposure to styrene or its metabolites styrene oxide or 4-vinylphenol

Harvilchuck, Jill A.; Zurbrugg, Rebekah J.; Carlson, Gary P.

doi:10.1016/j.toxlet.2008.09.010

Cited by 9 publications

(10 citation statements)

References 51 publications

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“…In the past, there was strong evidence that styrene-induced toxicity is related to oxidative stress (Harvilchuck et al, 2008(Harvilchuck et al, , 2009MeszkaJordan et al, 2009) and that this was likely due to the fact that styrene and styrene oxide produce significant decreases in liver and lung GSH levels (Turner et al, 2005;Carlson et al, 2006;Harvilchuck & Carlson, 2006). In the current studies styrene (600 mg/kg ip) markedly depleted GSH levels in both plasma and BALF within 3 h ( Table 1).…”

Section: Resultssupporting

confidence: 58%

“…This may be related to its metabolism to GSH conjugates. In addition, styrene has been associated with oxidative stress, which may be either the result of this GSH depletion or the cause of it (Harvilchuck & Carlson, 2006;Harvilchuck et al, 2008;). This was evidenced by increases in total reactive oxygen species (ROS) in the mouse Clara cell (135% of control 3 h after 600 mg/kg, ip styrene) as well as rises in 8-hydroxydeoxyguanosine (Harvilchuck et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…While these amounts are high in comparison to human exposures (Miller et al, 1994;Cohen et al, 2002), they have been used in previous studies by us (Gadberry et al, 1996;Carlson, 1997;Carlson et al, 2006;Harvilchuck et al, 2008;Meszka-Jordan et al, 2009) and others (Chakrabarti et al, 1993). Because of the limited solubility of styrene and styrene oxide in water, corn oil was used as the vehicle, and controls received an equivalent volume (1 ml/ 100 g).…”

Section: Experimental Designmentioning

confidence: 99%

“…Styrene (600 mg/kg) was found to produce decreases in GSH levels in Clara cells (Harvilchuck & Carlson, 2006), the lung cell type that is the most active in styrene metabolism (Hynes et al, 1999). The emphasis on GSH depletion is important since the action of styrene may be related to the production of oxidative stress (Harvilchuck et al, 2008(Harvilchuck et al, , 2009Meszka-Jordan et al, 2009).…”

mentioning

confidence: 99%

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

Carlson

2010

Journal of Toxicology and Environmental Health, Part A

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Styrene is a widely used chemical, but it is known to produce lung and liver damage in mice. This may be related to oxidative stress associated with the decrease in the levels of reduced glutathione (GSH) in the target tissues. The purpose of this study was to investigate the effect of styrene and its primary metabolites R-styrene oxide (R-SO) and S-styrene oxide (S-SO) on GSH levels in the lung lumen, as determined by amounts of GSH in bronchioalveolar lavage fluid (BALF) and in plasma. When non-Swiss albino (NSA) mice were administered styrene (600 mg/kg, ip), there was a significant fall in GSH levels in both BALF and plasma within 3 h. These returned to control levels by 12 h. The active metabolite R-SO (300 mg/kg, ip) also produced significant decreases in GSH in both BALF and plasma, but S-SO was without marked effect. Since GSH is a principal antioxidant in the lung epithelial lining fluid, this fall due to styrene may exert a significant influence on the ability of the lung to buffer oxidative damage.

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Section: Resultssupporting

confidence: 58%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

mentioning

confidence: 99%

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

Carlson

2010

Journal of Toxicology and Environmental Health, Part A

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“…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.…”

mentioning

confidence: 99%

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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Effect of multiple doses of styrene and R-styrene oxide on CC10, bax, and bcl-2 expression in isolated Clara cells of CD-1 mice

Harvilchuck

Carlson

2009

Toxicology

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CC10 mRNA and protein expression in Clara cells of CD-1 mice following exposure to styrene or its metabolites styrene oxide or 4-vinylphenol

Cited by 9 publications

References 51 publications

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

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

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

Effect of multiple doses of styrene and R-styrene oxide on CC10, bax, and bcl-2 expression in isolated Clara cells of CD-1 mice

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