Investigation of the Effect of Circadian Rhythm Disruption on the Efficacy of Metformin Treatment in Liver Tissue and Hepatic Enzyme Activity in Diabetic Rats
Authors
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Sahar Molzemi
- Student Research Committee, Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
https://orcid.org/0000-0003-3069-5926
- Ali Vahedi - Student Research Committee, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
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Pirasteh Norouzi
- School of Medicine, Shahroud University of Medical Sciences,Shahroud, Iran.
https://orcid.org/0000-0002-0691-1177
-
Alireza Masoudi*
- Department of Physiology and Pharmacology, School of Medicine, Shahroud University of Medical Sciences, Shahroud, Iran.
https://orcid.org/0000-0002-5598-9384
DOI:
https://doi.org/10.22100/jkh.v20i3.3495Abstract
Introduction: This study aimed to investigate the effects of circadian rhythm disruption and metformin treatment on liver enzymes (ALT, AST, and ALP) and hepatic tissue alterations in diabetic rats.
Methods: Thirty-six adult male Wistar rats were randomly divided into six groups (n=6). Lighting conditions included normal circadian rhythm (12 h light/12 h dark) and constant light (24 h light). The experimental groups consisted of: control (citrate buffer), diabetic rats induced by intraperitoneal injection of STZ (55 mg/kg), and diabetic rats treated orally with metformin (500 mg/kg, twice daily). Diabetes was confirmed by fasting blood glucose levels ≥300 mg/dl, and metformin treatment was continued for two weeks. At the end of the study, blood samples were collected from the heart under anesthesia, serum liver enzyme levels were measured by ELISA, and liver tissues were examined histologically using hematoxylin and eosin (H&E) staining.
Results: Constant light exposure significantly exacerbated diabetes-induced liver injury. Diabetes induction under both lighting conditions caused a significant increase in serum ALT, AST, and ALP levels compared to controls (P≤0.05). Constant light alone also elevated these enzyme levels. Metformin treatment under both lighting conditions significantly reduced serum liver enzyme levels compared to the respective diabetic groups (P≤0.05), indicating a protective effect. Histological findings confirmed severe hepatic damage (hepatocyte disorganization and vacuolization) in diabetic rats under constant light, while metformin treatment partially improved hepatic architecture.
Conclusion: Circadian rhythm disruption may exacerbate liver injury in diabetes, highlighting the importance of maintaining normal circadian patterns. Metformin, through its hepatoprotective effects, could be an effective treatment for diabetic patients with circadian disturbances.
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