TY - JOUR ID - 13886 TI - Thalidomide attenuates the hyporesponsiveness of isolated atria to chronotropic stimulation in BDL rats: The involvement of TNF-α, IL-6 inhibition, and SOCS1 activation JO - Iranian Journal of Basic Medical Sciences JA - IJBMS LA - en SN - 2008-3866 AU - Hosseini-chegeni, Ali AU - Jazaeri, farahnaz AU - Yousefi-Ahmadipour, Aliakbar AU - Heidari, Mansour AU - Abdollahi, Alireza AU - Dehpour, Ahmad Reza AD - Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran AD - Department of Laboratory of Sciences, Faculty of Paramedical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran AD - Department of Medical Genetics, Tehran University of Medical Sciences, Tehran, Iran AD - Department of Pathology, School of Medicine, Imam Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran Y1 - 2019 PY - 2019 VL - 22 IS - 11 SP - 1259 EP - 1266 KW - Cirrhotic cardiomyopathy KW - IL-6 KW - SOCS1 KW - Thalidomide KW - TNF-α DO - 10.22038/ijbms.2019.32256.7742 N2 - Objective(s): Cirrhotic cardiomyopathy is a complication of uncured cirrhosis which is associated with hyporesponsiveness of the heart to sympathetic stimulation. The enhancement of portal pressure, nitric oxide (NO) level, pro-inflammatory mediators and down-regulation of Suppressor of Cytokine Signaling 1 (SOCS1) are involved in this situations. The present study seeks to examine the beneficial effect of thalidomide on cirrhotic cardiomyopathy. Materials and Methods: The male rats were grouped as: Sham/saline, Sham/Thalidomide, Bile Duct Ligation (BDL)/saline and BDL/Thalidomide. BDL model of cirrhosis was used. In the treatment groups, thalidomide (200 mg/kg/day) was administrated by intragastrial gavage for 28 consecutive days, the chronotropic response was assessed in isolated atria by isoproterenol stimulation. Serum levels of NO, IL-6 and TNF-α hepatic level were evaluated. The intrasplenic pulp pressure (ISPP) as the portal pressure and histopathologic assessment were assessed. Real time RT-PCR was used for the evaluation of SOCS1 gene expression.Results: Our results showed that thalidomide administration could significantly increase the atrial chronotropic response in BDL animals. The increased level of portal pressure decreased by thalidomide in BDL animals. Thalidomide could ameliorate the histopathological conditions of BDL rats. Furthermore, the chronic treatment by this drug diminished the elevated levels of NO, TNF-α and IL-6 in BDL animals. On the other hand, hepatic SOCS1 expression was up-regulated by thalidomide treatment in this group. Conclusion: Thalidomide improves the chronotropic hyporesponsiveness of isolated atria in BDL. This effect is probably mediated by the inhibiting NO, TNF-α and IL-6 production, reducing portal pressure and increasing the expression of SOCS1. UR - https://ijbms.mums.ac.ir/article_13886.html L1 - https://ijbms.mums.ac.ir/article_13886_0783b44401da8d35992d9e5ddb361bea.pdf ER -