Colchicine alleviates steroid-induced Hyperglycemia and Dyslipidemia: Targeting Pyroptosis and Oxidative stress

Nageeb, Mahitab Mohamed; Mortada Mahmoud, Samar; Ali Mohamed Ali, Shimaa; Hendy, Nehal Ebrahim; M. Ahmad, Marwa; A. Hemead, dalia

doi:10.21608/zumj.2024.333297.3674

	Colchicine alleviates steroid-induced Hyperglycemia and Dyslipidemia: Targeting Pyroptosis and Oxidative stress
Zagazig University Medical Journal
Article 14, Volume 31, Issue 2, February 2025, Page 695-713 PDF (2.51 MB)
Document Type: Original Article
DOI: 10.21608/zumj.2024.333297.3674
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Authors
Mahitab Mohamed Nageeb ¹; Samar Mortada Mahmoud ²; Shimaa Ali Mohamed Ali³; Nehal Ebrahim Hendy⁴; Marwa M. Ahmad ⁵; dalia A. Hemead ⁶
¹Pharmacology department, faculty of medicine , zagazig university , Egypt
²lecturer of Anatomy, Faculty of Medicine, Zagazig University, Egypt
³Lecturer of Biochemistry, Faculty of Medicine, Al-Azhar University, Egypt
⁴Medical physiology department-Faculty of medicine-Zagazig university
⁵Assistant professor of Anatomy, Faculty of Medicine, Zagazig University, Egypt
⁶lecturer of Physiology, Faculty of Medicine, Zagazig University, Egypt
Abstract
Abstract Background Steroid-induced hyperglycemia (SIH) is one of the most important side effects of glucocorticoids. Colchicine is a medication used to manage inflammation with not yet fully understood mechanisms. This work aimed to investigate the potential protecting effect of colchicine against the development of SIH, and to spot the possible mechanisms involved in this action. Methods: 24 adults male Wistar rats were allocated into 4 equal groups; the Control group: obtained saline, the Colchicine Group: received oral colchicine (0.5mg/kg/day) for 10 days, the SIH group: received dexamethasone (1mg/Kg/day, i.p.) for 10 days, the Colchicine-treated SIH Group: received dexamethasone for 10 days simultaneous with colchicine in the same previous doses. At the end of our experimental period, HOMA-IR, serum levels of insulin, and glucose were measured. Also, NLRP-3, ASC, gasdermin, IL-1, caspase-1, 8-OHdG, mTOR, TGF-β1, and Smad-2 were evaluated. Furthermore, Histopathology of the liver and Pancreas was assessed. Results: Our study detected steroid-induced hyperglycemia with inflammation, oxidative stress, and deteriorated liver and pancreas structure. Treatment with colchicine greatly suppressed the NLRP3/ASC/gasdermin/IL-1/caspase-1 pathway. Moreover, colchicine declined TGF-β1, and Smad2 gene expression with normalization of glycemic parameters and histopathological disruption. Conclusion: according to our findings, colchicine is proposed as a potential inhibitor of SIH.
Keywords
Liver; Pancreas; NLRP-3; TGF-β1; ASC


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