Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels
Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial...
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Shiraz University of Medical Sciences
2022-07-01
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| Series: | Iranian Journal of Medical Sciences |
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| Online Access: | https://ijms.sums.ac.ir/article_48131_7e100372dc83344c396c029e6a28b4b0.pdf |
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| author | Gholamreza Bayat Roham Mazloom Seyed Ali Hashemi Khalil Pourkhalili Parviz Fallah Alireza Shams Parvaneh Esmaeili Azadeh Khalili |
| author_facet | Gholamreza Bayat Roham Mazloom Seyed Ali Hashemi Khalil Pourkhalili Parviz Fallah Alireza Shams Parvaneh Esmaeili Azadeh Khalili |
| author_sort | Gholamreza Bayat |
| collection | DOAJ |
| description | Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions. |
| first_indexed | 2024-04-13T13:54:32Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 0253-0716 1735-3688 |
| language | English |
| last_indexed | 2024-04-13T13:54:32Z |
| publishDate | 2022-07-01 |
| publisher | Shiraz University of Medical Sciences |
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| series | Iranian Journal of Medical Sciences |
| spelling | doaj.art-7100632d9d904f91afe511913aeedcec2022-12-22T02:44:15ZengShiraz University of Medical SciencesIranian Journal of Medical Sciences0253-07161735-36882022-07-0147436737810.30476/ijms.2021.90750.217248131Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium ChannelsGholamreza Bayat0Roham Mazloom1Seyed Ali Hashemi2Khalil Pourkhalili3Parviz Fallah4Alireza Shams5Parvaneh Esmaeili6Azadeh Khalili7Department of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj IranDepartment of Physiology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, IranDepartment of Medical Laboratory Sciences, School of Para-Medicine, Alborz University of Medical Sciences, Karaj, IranDepartment of Anatomy, School of Medicine, Alborz University of Medical Sciences, Karaj, IranEqlimDanesh Co. Ltd, Tehran, IranDepartment of Physiology-Pharmacology-Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, IranBackground: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05.Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions.https://ijms.sums.ac.ir/article_48131_7e100372dc83344c396c029e6a28b4b0.pdfsilymarinliver cirrhosiscardiomyopathiesreceptors, adrenergic, betacalcium channels, l-type |
| spellingShingle | Gholamreza Bayat Roham Mazloom Seyed Ali Hashemi Khalil Pourkhalili Parviz Fallah Alireza Shams Parvaneh Esmaeili Azadeh Khalili Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels Iranian Journal of Medical Sciences silymarin liver cirrhosis cardiomyopathies receptors, adrenergic, beta calcium channels, l-type |
| title | Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels |
| title_full | Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels |
| title_fullStr | Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels |
| title_full_unstemmed | Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels |
| title_short | Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels |
| title_sort | silymarin administration attenuates cirrhotic induced cardiac abnormality in the rats a possible role of β1 adrenergic receptors and l type voltage dependent calcium channels |
| topic | silymarin liver cirrhosis cardiomyopathies receptors, adrenergic, beta calcium channels, l-type |
| url | https://ijms.sums.ac.ir/article_48131_7e100372dc83344c396c029e6a28b4b0.pdf |
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