Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

Schuschke, Dale A.; Adeagbo, Ayotunde S.O.; Patibandla, Phani K.; Egbuhuzo, Uchechi; Fernández-Botrán, Rafael; Johnson, W. Thomas

doi:10.1007/s10753-009-9140-4

Cited by 16 publications

(12 citation statements)

References 33 publications

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“…We have previously used the regimen of 1.5 mg Cu/kg diet for 4 weeks starting at weaning to study the cardiovascular effects of marginal Cu intake [30-32]. The effect of the marginal Cu diet on systemic Cu status in the current study (Table 1) is similar to our previous results with this diet.…”

Section: Discussionsupporting

confidence: 84%

“…Previous work with this diet suggests that this concentration of Cu appears to be near the tipping point for several functional changes associated with inadequate dietary Cu. These changes include prolonged hemostasis [30], diminished vasoreactivity [31], and upregulation of the inflammatory protein COX-2 [32]. The diminished vasoreactivity is also seen in a long-term adult model of Cu deficiency [33] validating the use of the short-term weanling model.…”

Section: Discussionmentioning

confidence: 99%

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Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

Sakai

Shin

Schuster

et al. 2010

Biol Trace Elem Res

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Copper deficiency can cause a host of major cardiovascular complications including an augmented inflammatory response through effects on both neutrophils and the microvascular endothelium. In the present study, we evaluated the effect of marginal copper deficiency on the neutrophilic response to hepatic ischemia/reperfusion injury, a condition that induces an inflammatory response. Male weanling Sprague–Dawley rats were fed purified diets which were either copper-adequate (6.3 mg/kg) or copper-marginal (1.62 mg/kg) for 4 weeks prior to undergoing 90 min of partial hepatic ischemia followed by 8 h of reperfusion. Liver injury was assessed by serum levels of alanine aminotransferase and by liver histology. Liver neutrophil accumulation was determined by tissue myeloperoxidase content. There was no significant difference in liver injury between copper-adequate and copper-marginal rats. However, liver neutrophil accumulation was significantly increased in copper-marginal rats. These findings were confirmed histologically. Liver expression of the adhesion molecule, intercellular adhesion molecule-1 (ICAM-1), was increased in copper-marginal rats compared to copper-adequate rats. The results suggest that neutrophil accumulation is increased through enhanced ICAM-1 expression in liver of copper-marginal rats after ischemia/reperfusion, but that this does not result in increased liver injury.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

Sakai

Shin

Schuster

et al. 2010

Biol Trace Elem Res

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“…COX-1 is involved in the synthesis of PGs, which are responsible for platelet aggregation and gastric mucosal protection [20]. However, COX-2 is an inducible protein included in inflammatory reactions [21]. Gastric ulcers and other side effects related to NSAID usage occur as a result of COX-1 inhibition [10,22].…”

Section: Inhibition Of Prostaglandin Synthesismentioning

confidence: 99%

Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers

et al. 2010

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Indomethacin is an indol derivative, non-steroidal, anti-inflammatory drug with anti-inflammatory, analgesic, and antipyretic effects. Indomethacin became the first-choice drug to produce an experimental ulcer model as a result of having a higher ulcerogenic potential than other non-steroidal anti-inflammatory drugs (NSAIDs). There have been several conflicting reports about the ulcerogenic mechanism of indomethacin; the mechanism is still unclear. It has been suggested that indomethacin induces gastric damage via inhibiting the release of protective factors like cyclooxygenase-1 (COX-1), prostaglandin E2 (PGE2), bicarbonate, and mucus; increasing aggressive factors like acid; and increasing oxidant parameters while decreasing antioxidant parameters. Classic antiulcer drugs are known to produce antiulcer effects by activating against indomethacin (increasing PGE2, mucus, and bicarbonate production; inhibiting acid secretion; decreasing oxidant parameters; and increasing antioxidants). However, some antiulcer drugs have been shown to inhibit indomethacin-induced ulcers without affecting acid and mucus secretion or oxidant parameters, as well as to inhibit the production of protective factors like COX-1, PGE2, and bicarbonate, and to reduce antioxidant parameters. In order to resolve the contradictions in the abovementioned data, this review hypothesized a relationship between indomethacin-induced ulcers and alpha 2 adrenergic receptors. It is suggested that blockage of alpha 2 adrenergic receptors may be responsible for the increase in the aggressive factors induced by indomethacin, and stimulation of alpha 2 adrenergic receptors may be responsible for the increase of protective factors induced by antiulcer drugs.

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“…Zn is necessary for correct function of MMPs and PAPP-A. It was shown that Cu-deficient rats had higher level of isoprostanes as marker of oxidative stress compared to Cu normal rats [30]. However, it was also found that high levels of Cu and other metal elements impair oxidative stress [31].…”

Section: Introductionmentioning

confidence: 99%

Biochemical oxidative stress-related markers in patients with obstructive sleep apnea

et al. 2011

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SummaryBackgroundObstructive sleep apnea (OSA) is a condition contributing to oxidative stress. The aim of this study was to ascertain if there is any connection between OSA and novel oxidative stress-related markers. Matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), high sensitive C-reactive protein (hsCRP), pregnancy-associated plasma protein-A (PAPP-A), soluble receptors for advanced glycation end-products (sRAGE), zinc (Zn) and copper (Cu) were measured. Further biochemical markers were evaluated.Material/MethodsFifty-one men suspected for OSA indicated for night polygraphy were included. Apnea/hypopnea index (AHI), oxygen desaturation index (ODI), mean blood hemoglobin oxygen saturation (SpO2) and time of blood hemoglobin oxygen saturation below 90% (SpO2 <90%) were measured. Morning venous blood samples were taken.ResultsFor body mass index (BMI) we found strong positive correlation with levels of Cu, MMP-9, hsCRP and fibrinogen, and negative correlation with sRAGE. Concerning ventilation parameters, we found positive correlation of ODI and SpO2 <90% with markers MMP-9 and hsCRP. sRAGE level correlated with AHI and ODI negatively. SpO2 correlated negatively with Cu, MMP-9, hsCRP and fibrinogen. There was no correlation between ventilation parameters and markers MMP-2, PAPP-A and Zn. Compared to severity of OSA, there was significant difference in levels of hsCRP and Cu between patients with AHI ≤5 and AHI ≥30 independent of BMI.ConclusionsMMP-9, hsCRP, sRAGE and Cu seem to be strong predictors of oxidative stress in OSA patients. The strong correlation between oxidative stress-related markers and OSA is elucidated by connection of these to BMI, which is probably a primary condition of oxidative stress, but OSA is an additive condition.

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Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

Cited by 16 publications

References 33 publications

Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

Marginal Copper Deficiency Increases Liver Neutrophil Accumulation After Ischemia/Reperfusion in Rats

Different Mechanisms in Formation and Prevention of Indomethacin-induced Gastric Ulcers

Biochemical oxidative stress-related markers in patients with obstructive sleep apnea

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