Celecoxib exacerbates hepatic fibrosis and induces hepatocellular necrosis in rats treated with porcine serum |
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| Authors: | Hao Liu Wei Wei Xiang Li |
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| Institution: | 1. Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology in Anhui Province, Key Laboratory of Research and Development of Chinese Medicine in Anhui Province, Engineering Technology Research Center of Anti-inflammatory and Immunodrugs in Anhui Province, Scientific and Technological Team of Anti-inflammatory and immunopharmacology of Chinese Medicine in Anhui Province, Hefei 230032, Anhui Province, China;2. Department of Pharmacology, Bengbu Medical College, Bengbu 233000, China;1. Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;2. Cardiovascular Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, United States;3. The Bert W. Strassburger Lipid Center, Tel Aviv University, 52621 Hashomer Tel, Israel;4. Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, 52621 Hashomer Tel, Israel;5. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, United States;1. Department of Molecular Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;2. Department of Mediator and Signal Transduction Pharmacology, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;3. Department of Anatomy, Kitasato University School of Allied Health Sciences, Sagamihara, Kanagawa, Japan;4. Department of Matrix Biology and Regenerative Medicine, Kitasato University Graduate School of Medical Sciences, Sagamihara, Kanagawa, Japan;1. Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, United States;2. Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, United States;3. Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX, United States;1. Physiology and Experimental Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;2. Laboratory Medicine, Research Institute, The Hospital for Sick Children, Toronto, Canada;3. Department of Pharmacology, Faculty of Medicine, University of Toronto, ON, Canada;1. Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China;2. Department of Thoracic Surgery, First Hospital of Jilin University, Changchun 130021, China;3. Department of Surgery, China-Japan Union Hospital of Jilin University, Changchun 130033, China;4. Department of Anesthesiology, China-Japan Union Hospital of Jilin University, Changchun 130033, China |
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| Abstract: | Inhibitors against cyclooxygenase-2 (COX-2), an inducible enzyme that catalyzes prostaglandin synthesis, are widely used in clinical. However, the potential hepatic toxicity of COX-2 inhibitors remains incompletely investigated. We report in this study that a clinically available COX-2 inhibitor, celecoxib, exacerbates porcine serum (PS)-induced hepatic fibrosis and induces hepatocellular necrosis in an experimental liver fibrosis model. Histological results revealed that although celecoxib by itself did not cause notable hepatic damages, it markedly enhanced hepatic fibrosis that had been initiated by PS. While PS alone did not cause any necrotic change in liver cells, the addition of celecoxib resulted in hepatocellular necrosis in PS-treated animals. Notably, celecoxib enhanced reduction of plasma prostaglandin E2 (PGE2) levels induced by PS. Taken together, our results indicate that treatment with celecoxib may exacerbate liver fibrosis and cause hepatocellular necrosis. This may be associated with reduction in PGE2 as an inheritance consequence of inhibition of COX-2. |
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