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

Abstract

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.

Artemisia annuaLeaf Extract Attenuates Hepatic Steatosis and Inflammation in High-Fat Diet-Fed Mice

“… 32 COX-2 is involved in the development of NASH; the products of lipid peroxidation can mediate inflammatory cell recruitment by activating COX-2. 33 COX-2-mediated adipose tissue inflammation is crucial to the development of insulin resistance and fatty liver in HFD-induced obese rats. 34 Here, we also showed that HMGB1 and COX-2 levels, as well as collagen deposition, were markedly elevated in the HFD-fed mice, and we further showed that they were decreased by dietary AA extract.…”

Nimesulide, a cyclooxygenase-2 selective inhibitor, suppresses obesity-related non-alcoholic fatty liver disease and hepatic insulin resistance through the regulation of peroxisome proliferator-activated receptor γ

“…Nimesulide reduced the number of Kupffer cells infiltrating the liver and decreased the gene expression of MCP-1, which directs trafficking of immune cell to sites of tissue damage. The products of lipid peroxidation can mediate inflammatory recruitment by activating NF-κB and COX-2 ( 39 ). The activation of NF-κB was accompanied by the increased hepatic expression of several inflammatory cytokines [interleukin (IL)-1β, TNF-α and IL-6] and by an increase in plasma MCP-1 levels, all known to be NF-κB-dependent inflammatory cytokines ( 40 ).…”

Cyclooxygenase 2 in liver dysfunction and carcinogenesis: Facts and perspectives

“…Therefore, the impact of PGE 2 on the insulin-dependent changes in hepatic metabolism is controversial: Hsieh et al[21] reported that rats fed a fructose or high fat diet (HFD) and treated with COX-2 inhibitors improved muscle and fat IR[22]; however, in a different context Coll et al[23] reported that COX-2 inhibition exacerbates palmitate-induced inflammation and IR in skeletal muscle. There are also reports using murine models of NASH induced by high fat or methionine and choline-deficient (MCD) diet describing an increase in COX-2 expression and the beneficial effects after celecoxib or nitro-aspirin treatment[24]. The interaction between PGE 2 , IL-6 and the IR in hepatocytes has been studied by Henkel et al[25,26] reporting that PGE 2 enhanced fat accumulation and interrupted the intracellular signaling of insulin in hepatocytes through serine phosphorylation of IRS via EP3-receptor-dependent ERK1/2 activation.…”