Diosmin Alleviates Doxorubicin-Induced Liver Injury via Modulation of Oxidative Stress-Mediated Hepatic Inflammation and Apoptosis via NfkB and MAPK Pathway: A Preclinical Study
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
Affiliations
Abdullah F. AlAsmari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Metab Alharbi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Faleh Alqahtani
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Fawaz Alasmari
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Mohammed AlSwayyed
Department of Pathology, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
Sami I. Alzarea
Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka 72341, Saudi Arabia
Ibrahim A. Al-Alallah
Pathology and Clinical Laboratories Medicine, King Fahad Medical City, Riyadh 11451, Saudi Arabia
Adel Alghamdi
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Hassan M. Hakami
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Meshal K. Alyousef
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
Youssef Sari
Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USA
Nemat Ali
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 55760, Riyadh 11451, Saudi Arabia
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.
