Effect of Celecoxib on Immunological Liver Injury and Depression Induced by Specific Liver Antigen and Complete Freund’s Adjuvant in C57BL/6 Mice
Esraa Moustafa ELnahas Fotouh Kabil;
Abstract
Background and aim: Depression associating in patients with chronic liver diseases is a major treatment goal. This study aimed to evaluate the potential hepatoprotective and antidepressant effects of celecoxib in a model of immunological liver injury and depression in an experimental model of autoimmune hepatitis (EAH) in C57BL/6 mice.
Methods: EAH was induced by immunization with S-100 liver antigen emulsified in complete Freund’s antigen (CFA). Mice were randomly assigned as; control phosphate buffered saline (0.2 ml, ip) group; control CFA (0.2ml, ip) group; EAH (0.4ml, ip) group, the celecoxib (7.5mg/kg/d) treated group and the celecoxib (15mg/kg/d) treated group. Mice were assessed behaviorally (Novelty-suppressed test, tail suspension test, and locomotor assessment followed by forced swimming tests). Biochemical analysis of liver enzymes and hepatic hydroxyproline content. Histopathological evaluation of liver injury and hippocampus changes was performed. Immunohistochemical studies for tumor necrosis factor (TNF-α), nuclear factor kappa-B (NF-κB) and caspase-3 in both liver and hippocampus were done.
Results: EAH group exhibited significant depressive like changes. Significant increase in serum AST and hepatic hydroxyproline levels. Histopathological examination revealed signs of autoimmune hepatitis and hippocampus affection. This was accompanied by over expression of TNF-α and NF-κB in both liver and hippocampus tissues along with elevated caspase-3 activity.
The celecoxib (7.5mg/kg/d) dose significantly ameliorated the hepatic biochemical changes, depressive behaviors and both hepatic and hippocampal histopathological & immunohistochemical changes induced in EAH group. The celecoxib (15mg/kg/d) dose significantly ameliorated the behavioral changes and histopathological and immunohistochemical changes in hippocampus, with non-significant improvement in hepatic biochemical profile, histopathological and immunohistochemical changes induced in EAH group.
Conclusion:
The celecoxib (7.5mg/kg/d) dose through its anti-inflammatory effect may represent a new therapeutic approach to treat autoimmune hepatitis associated with depressive symptoms.
Key words: EAH, depression, S-100, complete Freund’s antigen, NF-κB, celecoxib.
Methods: EAH was induced by immunization with S-100 liver antigen emulsified in complete Freund’s antigen (CFA). Mice were randomly assigned as; control phosphate buffered saline (0.2 ml, ip) group; control CFA (0.2ml, ip) group; EAH (0.4ml, ip) group, the celecoxib (7.5mg/kg/d) treated group and the celecoxib (15mg/kg/d) treated group. Mice were assessed behaviorally (Novelty-suppressed test, tail suspension test, and locomotor assessment followed by forced swimming tests). Biochemical analysis of liver enzymes and hepatic hydroxyproline content. Histopathological evaluation of liver injury and hippocampus changes was performed. Immunohistochemical studies for tumor necrosis factor (TNF-α), nuclear factor kappa-B (NF-κB) and caspase-3 in both liver and hippocampus were done.
Results: EAH group exhibited significant depressive like changes. Significant increase in serum AST and hepatic hydroxyproline levels. Histopathological examination revealed signs of autoimmune hepatitis and hippocampus affection. This was accompanied by over expression of TNF-α and NF-κB in both liver and hippocampus tissues along with elevated caspase-3 activity.
The celecoxib (7.5mg/kg/d) dose significantly ameliorated the hepatic biochemical changes, depressive behaviors and both hepatic and hippocampal histopathological & immunohistochemical changes induced in EAH group. The celecoxib (15mg/kg/d) dose significantly ameliorated the behavioral changes and histopathological and immunohistochemical changes in hippocampus, with non-significant improvement in hepatic biochemical profile, histopathological and immunohistochemical changes induced in EAH group.
Conclusion:
The celecoxib (7.5mg/kg/d) dose through its anti-inflammatory effect may represent a new therapeutic approach to treat autoimmune hepatitis associated with depressive symptoms.
Key words: EAH, depression, S-100, complete Freund’s antigen, NF-κB, celecoxib.
Other data
| Title | Effect of Celecoxib on Immunological Liver Injury and Depression Induced by Specific Liver Antigen and Complete Freund’s Adjuvant in C57BL/6 Mice | Other Titles | تأثيرالسيليكوكسيب على الإصابة المناعية للكبد والاكتئاب المُحْدَث بواسطة مُسْتَضِدّ محدد للكبد ومساعد فروند المتكامل على فئرانC57BL/6 | Authors | Esraa Moustafa ELnahas Fotouh Kabil | Issue Date | 2016 |
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