Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats

Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this stu...

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Main Authors: Gyas Khan, Mohammad Firoz Alam, Saeed Alshahrani, Yosif Almoshari, Abdulmajeed M. Jali, Saud Alqahtani, Mohammad Khalid, Shehla Nasar Mir Najib Ullah, Tarique Anwer
Format: Article
Language:English
Published: MDPI AG 2023-04-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/13/5/750
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author Gyas Khan
Mohammad Firoz Alam
Saeed Alshahrani
Yosif Almoshari
Abdulmajeed M. Jali
Saud Alqahtani
Mohammad Khalid
Shehla Nasar Mir Najib Ullah
Tarique Anwer
author_facet Gyas Khan
Mohammad Firoz Alam
Saeed Alshahrani
Yosif Almoshari
Abdulmajeed M. Jali
Saud Alqahtani
Mohammad Khalid
Shehla Nasar Mir Najib Ullah
Tarique Anwer
author_sort Gyas Khan
collection DOAJ
description Trastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone’s cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.
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spelling doaj.art-8d61807a6c5b44fda223ad672b2398292023-11-18T02:03:35ZengMDPI AGJournal of Personalized Medicine2075-44262023-04-0113575010.3390/jpm13050750Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in RatsGyas Khan0Mohammad Firoz Alam1Saeed Alshahrani2Yosif Almoshari3Abdulmajeed M. Jali4Saud Alqahtani5Mohammad Khalid6Shehla Nasar Mir Najib Ullah7Tarique Anwer8Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj 16278, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Khalid University, Abha 61421, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan 45142, Saudi ArabiaTrastuzumab (TZB) is a new medicine, used to treat cancers of the breast and stomach. However, the cardiotoxic potential of this drug edges out its clinical advantages. The present study was designed to find out the effect of zingerone against trastuzumab-mediated cardiotoxicity in rats. In this study, five groups of rats with eight animals in each group were used. Group 1 was treated with normal saline, as a normal control (NC); Group 2 was treated with TZB (6 mg/kg/week-for five weeks) intraperitoneally as a toxic control. Groups 3 and 4 were pre-treated with zingerone (50 and 100 mg/kg, as per their body weight orally) along with five doses of TZB for five weeks, and Group 5 was treated with zingerone (100 mg/kg, body weight orally) as a control. TZB treatment showed cardiotoxicity as evidenced by increased levels of aspartate aminotransferase (AST), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), and lipid peroxidation (LPO) and decreased level of glutathione (GSH), and antioxidant enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s- transferase (GST), catalase (CAT), and superoxide dismutase (SOD) activities. Zingerone pre-treatment significantly decreased the levels of AST, CK-MB, LDH, and LPO and increased GSH and antioxidant enzymes content toward their normal level. In the TZB-alone administered group, inflammatory cytokines (IL-2 and TNF-α) levels were also elevated. Pre-treatment with zingerone restored the level of IL-2 and TNF-α toward normal level. The current findings undoubtedly demonstrated zingerone’s cardioprotective nature against TZB-mediated cardiotoxicity in rats with the evidence of histopathological recall.https://www.mdpi.com/2075-4426/13/5/750zingeronetrastuzumabcardiotoxicityinterleukinIL-2 and TNF-αhistopathology
spellingShingle Gyas Khan
Mohammad Firoz Alam
Saeed Alshahrani
Yosif Almoshari
Abdulmajeed M. Jali
Saud Alqahtani
Mohammad Khalid
Shehla Nasar Mir Najib Ullah
Tarique Anwer
Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
Journal of Personalized Medicine
zingerone
trastuzumab
cardiotoxicity
interleukin
IL-2 and TNF-α
histopathology
title Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
title_full Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
title_fullStr Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
title_full_unstemmed Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
title_short Trastuzumab-Mediated Cardiotoxicity and Its Preventive Intervention by Zingerone through Antioxidant and Inflammatory Pathway in Rats
title_sort trastuzumab mediated cardiotoxicity and its preventive intervention by zingerone through antioxidant and inflammatory pathway in rats
topic zingerone
trastuzumab
cardiotoxicity
interleukin
IL-2 and TNF-α
histopathology
url https://www.mdpi.com/2075-4426/13/5/750
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