Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium-Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats

Layla A Alahmari; Lashin S Ali; Hoda A Fansa; Dalal S Alshaya; Fawziah A Al-Salmi; Ehab I El-Hallous; Mamdouh Eldesoqui; Fahmy Gad Elsaid; Eman Fayad; Ahmed A El-Mansy; Ghadi Alsharif; Dlovan Y Khalil; Maryam Bakir Mahmood; Rozhan Yassin Khalil; Hanan M Rashwan; Shady G El-Sawah

doi:10.1002/jez.2881

Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium-Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats

J Exp Zool A Ecol Integr Physiol. 2024 Nov 13. doi: 10.1002/jez.2881. Online ahead of print.

Authors

Layla A Alahmari¹, Lashin S Ali^{2

3}, Hoda A Fansa^{4

5}, Dalal S Alshaya⁶, Fawziah A Al-Salmi⁷, Ehab I El-Hallous^{7

8}, Mamdouh Eldesoqui⁹, Fahmy Gad Elsaid¹⁰, Eman Fayad¹¹, Ahmed A El-Mansy^{12

13}, Ghadi Alsharif^{14

15}, Dlovan Y Khalil¹⁶, Maryam Bakir Mahmood¹⁷, Rozhan Yassin Khalil¹⁷, Hanan M Rashwan⁸, Shady G El-Sawah⁸

Affiliations

¹ Department of Community Health, College of Applied Medical Sciences, Northern Border University, Arar, Saudi Arabia.
² Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan.
³ Physiology Department, Faculty of Medicine, Mansoura University, Mansours, Egypt.
⁴ Department of Basic Dental Sciences, Faculty of Dentistry, Al-Ahliyya Amman University, Amman, Jordan.
⁵ Department of Oral Biology, Faculty of Dentistry, Alexandria University, Egypt.
⁶ Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
⁷ Department of Biology, College of Science, Taif University, Taif, Saudi Arabia.
⁸ Zoology Department, Faculty of Science, Arish University, North Sinai, Egypt.
⁹ Department of Basic Medical Sciences, College of Medicine, AlMaarefa University, Diriyah, Riyadh, Saudi Arabia.
¹⁰ Department of Biology, College of Science, King Khalid University, Asir, Abha, Saudi Arabia.
¹¹ Department of Biotechnology, College of Science, Taif University, Taif, Saudi Arabia.
¹² Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqa University, Zarqa, Jordan.
¹³ Department of Medical Histology & Cell Biology, Faculty of Medicine, Mansoura University, Mansours, Egypt.
¹⁴ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud Bin Abdulaziz University of Health Sciences, Jeddah, Saudi Arabia.
¹⁵ Department of Biomedical Research, King Abdullah International Medical Research Center, Jeddah, Saudi Arabia.
¹⁶ Biology Department, Faculty of Science, Sulaimani University, Sulaimaniyah, Iraq.
¹⁷ Obstetrics & Gynecology Department, College of Medicine, Slaimani University, Sulaymaniyah, Iraq.

PMID: 39535481
DOI: 10.1002/jez.2881

Abstract

Mesenchymal stem cells-derived exosomes (MSCs-EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs-EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4-weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ-diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic-treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H₂O₂) inflammatory (IL-6, TNF-α, and TGF-β), and apoptotic (P53, BAX, caspase-3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.

Keywords: diabetes mellitus; exosomes (EXs); mesenchymal stem cells; nano selenium.

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research and Graduate Studies at King Khalid University for funding this work through the Large Research Project under grant number RGP2/61/45. The authors extend their appreciation to the Deanship of Scientific Research of Princess Nourah bint Abdulrahman University, Researchers Supporting Project number (PNURSP2024R465), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.