Effect of Celecoxib, a Selective Cyclooxygenase-2 Inhibitor on Carbon Tetrachloride Intoxication in Rats

Washino, Yukiko; Koga, Eriko; Kitamura, Yuko; Kamikawa, Chiaki; Kobayashi, Kazuo; Nakagawa, Tomoka; Nakazaki, Chihiro; Ichi, Ikuyo; Kojo, Shosuke

doi:10.1248/bpb.33.707

Cited by 9 publications

(8 citation statements)

References 31 publications

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“…33) Then, it is reasonable that inhibiting only COX-2, a component in this exacerbation cycle, ameliorated hepatitis in the COX-2 transgenic mice 33) as well as in CCl 4 -administered rats. 34) Therefore it is conceivable that the reduced number of Kupffer cells and resulting decrease in TNF-α release intercepted the exacerbation cycle in KO mice.…”

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confidence: 99%

The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

Kiso

Ueno

Fukuda

et al. 2012

Biological & Pharmaceutical Bulletin

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Carbon tetrachloride (CCl 4 )-induced acute hepatitis is assumed to involve two phases. The initial phase, initiated within 2 h after CCl 4 administration, involves the generation of reactive oxygen species. The second phase is assumed to start about 8 h subsequent to CCl 4 administration and involves the oxidant-induced activation of Kupffer cells, which release various pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). We investigated the role of Kupffer cells during CCl 4 intoxication using Nucling-knockout mice (the KO group), in which the number of Kupffer cells is largely reduced. Plasma alanine transaminase and aspartate transaminase levels demonstrated that the liver necrosis during the second phase was significantly alleviated in the KO group compared with that in the wild-type mice (the WT group). Plasma TNF-α concentrations in the WT group significantly increased 24 h after CCl 4 intoxication, whereas those in the KO group did not significantly increase. Plasma IL-6 levels also significantly increased in the WT group 24 h after CCl 4 administration, but those in the KO group did not increase at any time point. These results indicated that excess reactions of Kupffer cells, once primed by oxidants, were involved in the exacerbation of oxidative stress and liver damage during the second phase of CCl 4 intoxication.

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Section: )mentioning

confidence: 99%

The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

Kiso

Ueno

Fukuda

et al. 2012

Biological & Pharmaceutical Bulletin

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“…COX-2 is expressed only at low levels in normal hepatocytes, whereas it is markedly increased in chronic hepatitis and liver cirrhosis (3,4). It has been reported that the selective inhibitor of COX-2, celecoxib (20 mg/kg/day), reduced hepatic fibrosis in both CCl4-, BDL-and TAA-treated rats (5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

Celecoxib attenuates liver steatosis and inflammation in non-alcoholic steatohepatitis induced by high-fat diet in rats

et al. 2011

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Abstract. Cyclooxygenase-2 (COX-2) is involved in the process of non-alcoholic steatohepatitis (NASH). However, the role of the COX-2 inhibitor in NASH has not yet been elucidated. Therefore, in the present sudy, we investigated the role of celecoxib in a rat model of NASH induced by a high-fat diet (HFD). Wistar rats were administered HFD by gavage, and rats administered normal saline by gavage served as the controls. After 4 weeks of HFD feeding, the rats were treated with celecoxib (20 mg/kg/day) or placebo for 4 weeks. At the end of 4 and 8 weeks, histological changes in the livers of the rats were analyzed using hematoxylin and eosin; blood was collected to detect biochemical indicators (serum aminotransferase and triglyceride). Liver triglyceride content was measured using the triglyceride E-test kit. The liver expression of COX-2, nuclear factor-κ enhancer binding protein (NF-κB) subunits p50 and p65 was measured by real-time reverse transcription-polymerase chain reaction and/or Western blotting. Infiltration of steatosis and inflammation in cells was observed in the livers after 4 weeks of HFD administration, and marked steatosis and inflammation was induced after 8 weeks. These histological changes were significantly attenuated after celecoxib treatment. Reduced serum alanine aminotransferase and triglyceride (TG) levels and TG content in the liver were observed in the HFD rats that received celecoxib. Moreover, celecoxib suppressed hepatic COX-2 messenger RNA and protein expression. The NF-κB subunit p50 and p65 protein levels in the HFD rats were also attenuated after celecoxib treatment. The results indicate that the induction of COX-2 occurs in association with NF-κB activation in HFD-induced NASH rats. Celecoxib may protect against the development of steatohepatitis induced by HFD.

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“…Relevant to this study, opposing results have been reported in CCl 4 models of liver fibrosis. In a short-term model, celecoxib reduced liver inflammation and damage during the early phase of CCl 4 toxicity (Washino et al, 2010). A similar short-term study found that celecoxib reduced markers of lipid peroxidation but had no effect on hepatic toxicity or necrosis (Ekor et al, 2013).…”

Section: Discussionmentioning

confidence: 93%

Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride–Induced Model of Liver Injury

et al. 2018

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The cyclooxygenase-2 (COX-2) selective inhibitor celecoxib is widely used in the treatment of pain and inflammation. Celecoxib has been explored as a possible treatment of liver fibrosis with contradictory results, depending on the model. The present study reports the effect of celecoxib in a 5-week carbon tetrachloride (CCl)-induced liver fibrosis mouse model. Celecoxib alone and in combination with inhibitors of the enzyme-soluble epoxide hydrolase (sEH), as well as a dual inhibitor that targets both COX-2 and sEH, were administered via osmotic minipump to mice receiving intraperitoneal injections of CCl Collagen deposition was elevated in the mice treated with both celecoxib and CCl compared with the control or CCl-only groups, as assessed by trichrome staining. Histopathology revealed more extensive fibrosis and cell death in the animals treated with both celecoxib and CCl compared with all other experimental groups. Although some markers of fibrosis, such as matrix metalloprotease, were unchanged or lowered in the animals treated with both celecoxib and CCl, overall, hepatic fibrosis was more severe in this group. Cotreatment with celecoxib and an inhibitor of sEH or treatment with a dual inhibitor of COX-2 and sEH decreased the elevated levels of fibrotic markers observed in the group that received both celecoxib and CCl Oxylipid analysis revealed that celecoxib reduced the level of prostaglandin E relative to the CCl only group. Overall, celecoxib treatment did not decrease liver fibrosis in CCl-treated mice.

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Effect of Celecoxib, a Selective Cyclooxygenase-2 Inhibitor on Carbon Tetrachloride Intoxication in Rats

Cited by 9 publications

References 31 publications

The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice

Celecoxib attenuates liver steatosis and inflammation in non-alcoholic steatohepatitis induced by high-fat diet in rats

Celecoxib Does Not Protect against Fibrosis and Inflammation in a Carbon Tetrachloride–Induced Model of Liver Injury

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