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Hepatoprotective Effects of Polydatin-Loaded Chitosan Nanoparticles in Diabetic Rats: Modulation of Glucose Metabolism, Oxidative Stress, and Inflammation Biomarkers

Abeer M. Abd El-Hameed1,a, Ahmed I. Yousef2,b, Sanaa M. Abd El-Twab2,c, Ahmed A. G. El-Shahawy3,d, and Adel Abdel-Moneim2,e*

1Chemistry Department, Faculty of Science, Taibah University, 30002 Al-Madinah Al-Munawarah, Saudi Arabia

2Molecular Physiology Division, Faculty of Science, Beni-Suef University, 62511 Beni-Suef, Egypt

3Materials Science and Nanotechnology Department, Faculty of Postgraduate Studies for Advanced Sciences (PSAS), Beni-Suef University, 62511 Beni-Suef, Egypt

* To whom correspondence should be addressed.

Received June 15, 2020; Revised September 3, 2020; Accepted September 9, 2020
Polydatin (PD) has a broad range of pharmacological activities; however, its effects on diabetic liver damage are poorly studies. This work is aimed to explore possible protective effects of polydatin-loaded chitosan nanoparticles (PD-CSNPs) or PD against liver damage associated with diabetes. Diabetes was induced in rats using nicotinamide/streptozotocin treatment. Diabetic rats were then divided into six groups: normal control rats, diabetic control rats, and rats orally treated with PD, PD-CSNPs, equivalent unloaded CSNPs, or metformin daily for 4 weeks. Treatment with PD and PD-CSNPs significantly reduced the blood glucose content, lipid peroxidation in the liver, and activities of serum transaminases and carbohydrate metabolism enzymes (including succinate dehydrogenase and pyruvate kinase); by contrast, liver glycogen content, glutathione concentration, and activities of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase, and glucose-6-phosphate dehydrogenase) were markedly increased compared with the control diabetic rats. Furthermore, expression of the tumor necrosis factor α and interleukin-1β mRNAs was significantly downregulated, while expression of glucose transporter 2 and glucokinase mRNAs was strongly upregulated vs. control diabetic rats. We concluded that PD-CSNPs and PD ameliorate diabetic liver damage by modulating glucose transporter 2 expression, affecting the activity of carbohydrate metabolism enzymes, and suppressing oxidative stress and inflammation, PD-CSNPs being more efficient than PD, probably due to higher bioavailability and prolonged release.
KEY WORDS: diabetic liver damage, polydatin-loaded chitosan nanoparticles, carbohydrate metabolism enzymes, glucose transporter 2, oxidative stress

DOI: 10.1134/S0006297921020061