Toxicity and therapeutic property of dioxopiperidin derivative SKT40 demonstrated in-vivo zebrafish model due to inflammatory bowel disease.

Autor: Aswinanand B; Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India., Nayak SPRR; Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India., Madesh S; Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India., Subbarayudu S; Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India., Kaliraj S; Department of Chemistry, Faculty of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India., Rajagopal R; Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Alfarhan A; Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia., Kathiravan MK; Department of Pharmaceutical Chemistry, SRM School of Pharmacy, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India. Electronic address: kathirak@srmist.edu.in., Arockiaraj J; Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Technology, SRM Institute of Science and Technology, Kattankulathur 603203, Chengalpattu District, Tamil Nadu, India. Electronic address: jesuaroa@srmist.edu.in.
Jazyk: angličtina
Zdroj: Comparative biochemistry and physiology. Toxicology & pharmacology : CBP [Comp Biochem Physiol C Toxicol Pharmacol] 2024 Oct; Vol. 284, pp. 109990. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1016/j.cbpc.2024.109990
Abstrakt: Inflammatory bowel disease (IBD) encompasses chronic disorders that cause severe inflammation in the digestive tract. This study evaluates (E)-3-(3,4-dichlorophenyl)-N-(2,6-dioxopiperidin-3-yl) acrylamide (named SKT40), a derivative of dioxopiperidinamide, as a potential novel treatment for IBD. The pharmacological activity of SKT40 indicated positive interactions using network pharmacology and molecular docking in silico. In vivo, adult and larval zebrafish were tested to evaluate the effectiveness of SKT40 at different concentrations (7.5 μM, 10 μM, 15 μM) in preventing dextran sulfate sodium (DSS)-induced intestinal inflammation. The administration of SKT40 resulted in positive effects by reducing reactive oxygen species (ROS), lipid peroxidation, and cell apoptosis in zebrafish larvae. SKT40 demonstrated a significant reduction in intestinal damage in adult zebrafish by increasing antioxidant enzymes that combat the causes of IBD, such as superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). It also reduces cellular damage and inflammation, as indicated by decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA). Gene expression analysis identified downregulation in gene expression of inflammatory mediators such as TNF-α, IL-1β, COX-2, and IL-6. Histopathological analysis showed tissue repair from DSS-induced damage and indicated reduced hyperplasia of goblet cells. These findings suggest that SKT40 effectively treats intestinal damage, highlighting its potential as a promising candidate for IBD therapy.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: