Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study
Hepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups:...
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2021-12-01
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| author | Abdullah F. AlAsmari Metab Alharbi Faleh Alqahtani Fawaz Alasmari Mohammed AlSwayyed Sami I. Alzarea Ibrahim A. Al-Alallah Adel Alghamdi Hassan M. Hakami Meshal K. Alyousef Youssef Sari Nemat Ali |
| author_facet | Abdullah F. AlAsmari Metab Alharbi Faleh Alqahtani Fawaz Alasmari Mohammed AlSwayyed Sami I. Alzarea Ibrahim A. Al-Alallah Adel Alghamdi Hassan M. Hakami Meshal K. Alyousef Youssef Sari Nemat Ali |
| author_sort | Abdullah F. AlAsmari |
| collection | DOAJ |
| description | Hepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups: Group I was served as control, Group II was treated with doxorubicin (20 mg/kg, intraperitoneal, i.p.), Group III was treated with a combination of doxorubicin and low-dose diosmin (100 mg/kg orally), and Group IV was treated with a combination of doxorubicin and high-dose diosmin (200 mg/kg orally) supplementation. A single dose of doxorubicin (i.p.) caused hepatic impairment, as shown by increases in the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Doxorubicin produced histological abnormalities in the liver. In addition, a single injection of doxorubicin increased lipid peroxidation and reduced glutathione, catalase, and superoxide dismutase (SOD) levels. Importantly, pre-treatment with diosmin restored hepatic antioxidant factors and serum enzymatic activities and reduced the inflammatory and apoptotic-mediated proteins and genes. These findings demonstrate that diosmin has a protective effect against doxorubicin-induced hepatotoxicity. |
| first_indexed | 2024-03-10T04:38:37Z |
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| id | doaj.art-752488e3504544d1be6855657fc08e05 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T04:38:37Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-752488e3504544d1be6855657fc08e052023-11-23T03:34:07ZengMDPI AGAntioxidants2076-39212021-12-011012199810.3390/antiox10121998Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical StudyAbdullah F. AlAsmari0Metab Alharbi1Faleh Alqahtani2Fawaz Alasmari3Mohammed AlSwayyed4Sami I. Alzarea5Ibrahim A. Al-Alallah6Adel Alghamdi7Hassan M. Hakami8Meshal K. Alyousef9Youssef Sari10Nemat Ali11Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pathology, College of Medicine, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi ArabiaPathology and Clinical Laboratories Medicine, King Fahad Medical City, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USADepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi ArabiaHepatotoxicity caused by chemotherapeutic drugs (e.g., doxorubicin) is of critical concern in cancer therapy. This study focused on investigating the modulatory effects of diosmin against doxorubicin-induced hepatotoxicity in Male Wistar rats. Male Wistar rats were randomly divided into four groups: Group I was served as control, Group II was treated with doxorubicin (20 mg/kg, intraperitoneal, i.p.), Group III was treated with a combination of doxorubicin and low-dose diosmin (100 mg/kg orally), and Group IV was treated with a combination of doxorubicin and high-dose diosmin (200 mg/kg orally) supplementation. A single dose of doxorubicin (i.p.) caused hepatic impairment, as shown by increases in the concentrations of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase. Doxorubicin produced histological abnormalities in the liver. In addition, a single injection of doxorubicin increased lipid peroxidation and reduced glutathione, catalase, and superoxide dismutase (SOD) levels. Importantly, pre-treatment with diosmin restored hepatic antioxidant factors and serum enzymatic activities and reduced the inflammatory and apoptotic-mediated proteins and genes. These findings demonstrate that diosmin has a protective effect against doxorubicin-induced hepatotoxicity.https://www.mdpi.com/2076-3921/10/12/1998diosmindoxorubicinhepatotoxicityoxidative stressinflammationapoptosis |
| spellingShingle | Abdullah F. AlAsmari Metab Alharbi Faleh Alqahtani Fawaz Alasmari Mohammed AlSwayyed Sami I. Alzarea Ibrahim A. Al-Alallah Adel Alghamdi Hassan M. Hakami Meshal K. Alyousef Youssef Sari Nemat Ali Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study Antioxidants diosmin doxorubicin hepatotoxicity oxidative stress inflammation apoptosis |
| title | Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study |
| title_full | Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study |
| title_fullStr | Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study |
| title_full_unstemmed | Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study |
| title_short | Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study |
| title_sort | diosmin alleviates doxorubicin induced liver injury via modulation of oxidative stress mediated hepatic inflammation and apoptosis via nfkb and mapk pathway a preclinical study |
| topic | diosmin doxorubicin hepatotoxicity oxidative stress inflammation apoptosis |
| url | https://www.mdpi.com/2076-3921/10/12/1998 |
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