Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques

Toxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acu...

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Main Authors: Muhammad Kamil, Arifa Fatima, Sami Ullah, Gowhar Ali, Rasool Khan, Naila Ismail, Mughal Qayum, Marius Irimie, Catalina Georgeta Dinu, Hanadi Talal Ahmedah, Maria Elena Cocuz
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Toxics
Subjects:
Online Access:https://www.mdpi.com/2305-6304/9/6/119
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author Muhammad Kamil
Arifa Fatima
Sami Ullah
Gowhar Ali
Rasool Khan
Naila Ismail
Mughal Qayum
Marius Irimie
Catalina Georgeta Dinu
Hanadi Talal Ahmedah
Maria Elena Cocuz
author_facet Muhammad Kamil
Arifa Fatima
Sami Ullah
Gowhar Ali
Rasool Khan
Naila Ismail
Mughal Qayum
Marius Irimie
Catalina Georgeta Dinu
Hanadi Talal Ahmedah
Maria Elena Cocuz
author_sort Muhammad Kamil
collection DOAJ
description Toxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acute and sub-acute toxicity were assessed after intraperitoneal (i.p) injection of the investigational compound through selected doses for 21 days. This was followed by assessment of isolated body organs (liver, kidney, heart and pancreas) via biochemical indicators and histopathological techniques. No signs of toxicity were revealed in the study of acute toxicity. Similarly, a sub-acute toxicity study showed no significant difference in biochemical indicators on 11th and 21st days between treated and control groups. However, in blood urea nitrogen (BUN) and random blood glucose/sugar (RBS) values, significant differences were recorded. Histopathological evaluation of liver, kidney, pancreas and heart tissues revealed mild to severe changes in the form of steatosis, inflammation, fibrosis, necrosis and myofibrillary damages on 11th and 21st days of treatment. In conclusion, the median lethal dose of the tested compound was expected to be greater than 500 mg/kg. No significant change occurred in selected biomarkers, except BUN and RBS levels, but a histopathological study showed moderate toxic effect on liver, kidney, pancreas and heart tissues by the cyclohexenone derivative.
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spelling doaj.art-954f3bccbd8f46a99c5058b6b7eab13a2023-11-21T21:21:32ZengMDPI AGToxics2305-63042021-05-019611910.3390/toxics9060119Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical TechniquesMuhammad Kamil0Arifa Fatima1Sami Ullah2Gowhar Ali3Rasool Khan4Naila Ismail5Mughal Qayum6Marius Irimie7Catalina Georgeta Dinu8Hanadi Talal Ahmedah9Maria Elena Cocuz10Department of Pharmacy, University of Peshawar, Peshawar 25120, PakistanDepartment of Pharmacy, University of Peshawar, Peshawar 25120, PakistanDepartment of Pharmacy, University of Peshawar, Peshawar 25120, PakistanDepartment of Pharmacy, University of Peshawar, Peshawar 25120, PakistanDepartment of Organic Chemistry, Institute of Chemical Sciences, University of Peshawar, Peshawar 25120, PakistanDepartment of Pathology, Kabir Medical College, Gandhara University, Peshawar 25000, PakistanDepartment of Pharmacy, Kohat University of Science and Technology, Kohat 26000, PakistanFaculty of Medicine, Transilvania University of Brasov, 500019 Brasov, RomaniaFaculty of Law, Transilvania University of Brasov, 500019 Brasov, RomaniaDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Rabigh 25732, Saudi ArabiaFaculty of Medicine, Transilvania University of Brasov, 500019 Brasov, RomaniaToxicity studies were conducted to provide safety data of potential drug candidates by determining lethal and toxic doses. This study was designed for pre-clinical evaluation of novel cyclohexenone derivative with respect to the acute and sub-acute toxicity along with the diabetogenic potential. Acute and sub-acute toxicity were assessed after intraperitoneal (i.p) injection of the investigational compound through selected doses for 21 days. This was followed by assessment of isolated body organs (liver, kidney, heart and pancreas) via biochemical indicators and histopathological techniques. No signs of toxicity were revealed in the study of acute toxicity. Similarly, a sub-acute toxicity study showed no significant difference in biochemical indicators on 11th and 21st days between treated and control groups. However, in blood urea nitrogen (BUN) and random blood glucose/sugar (RBS) values, significant differences were recorded. Histopathological evaluation of liver, kidney, pancreas and heart tissues revealed mild to severe changes in the form of steatosis, inflammation, fibrosis, necrosis and myofibrillary damages on 11th and 21st days of treatment. In conclusion, the median lethal dose of the tested compound was expected to be greater than 500 mg/kg. No significant change occurred in selected biomarkers, except BUN and RBS levels, but a histopathological study showed moderate toxic effect on liver, kidney, pancreas and heart tissues by the cyclohexenone derivative.https://www.mdpi.com/2305-6304/9/6/119cyclohexenone derivativetoxic effectsliverkidneypancreasheart
spellingShingle Muhammad Kamil
Arifa Fatima
Sami Ullah
Gowhar Ali
Rasool Khan
Naila Ismail
Mughal Qayum
Marius Irimie
Catalina Georgeta Dinu
Hanadi Talal Ahmedah
Maria Elena Cocuz
Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
Toxics
cyclohexenone derivative
toxic effects
liver
kidney
pancreas
heart
title Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
title_full Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
title_fullStr Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
title_full_unstemmed Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
title_short Toxicological Evaluation of Novel Cyclohexenone Derivative in an Animal Model through Histopathological and Biochemical Techniques
title_sort toxicological evaluation of novel cyclohexenone derivative in an animal model through histopathological and biochemical techniques
topic cyclohexenone derivative
toxic effects
liver
kidney
pancreas
heart
url https://www.mdpi.com/2305-6304/9/6/119
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