Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

Khalaf F Alsharif; Asmaa A Hamad; Mohamed A Alblihd; Fatma Abo Zakaib Ali; Sherine Ahmed Mohammed; Abdulrahman Theyab; Osama M Al-Amer; Malik Saad Almuqati; Abdulraheem Ali Almalki; Alaa Jameel A Albarakati; Khalid J Alzahrani; Ashraf Albrakati; Mohammad Hamed Albarakati; Doaa Abass; Maha S Lokman; Ehab Kotb Elmahallawy

doi:10.3389/fvets.2023.1214533

Melatonin downregulates the increased hepatic alpha-fetoprotein expression and restores pancreatic beta cells in a streptozotocin-induced diabetic rat model: a clinical, biochemical, immunohistochemical, and descriptive histopathological study

Front Vet Sci. 2023 Aug 16:10:1214533. doi: 10.3389/fvets.2023.1214533. eCollection 2023.

Authors

Khalaf F Alsharif^#^{1

2}, Asmaa A Hamad^{2

3}, Mohamed A Alblihd^{2

4}, Fatma Abo Zakaib Ali⁵, Sherine Ahmed Mohammed⁶, Abdulrahman Theyab^{7

8}, Osama M Al-Amer^{9

10}, Malik Saad Almuqati¹¹, Abdulraheem Ali Almalki¹², Alaa Jameel A Albarakati¹³, Khalid J Alzahrani¹, Ashraf Albrakati¹⁴, Mohammad Hamed Albarakati¹⁵, Doaa Abass¹⁶, Maha S Lokman^{17

18}, Ehab Kotb Elmahallawy^#^{19

20}

Affiliations

¹ Department of Clinical Laboratories Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
² High Altitude Research Center, Taif University, Taif, Saudi Arabia.
³ Department of Biology, College of Science, Taif University, Taif, Saudi Arabia.
⁴ Department of Medical Microbiology and Immunology, College of Medicine, Taif University, Taif, Saudi Arabia.
⁵ Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.
⁶ Department of Histology, Faculty of Medicine, Sohag University, Sohag, Egypt.
⁷ Department of Laboratory and Blood Bank, Security Forces Hospital, Mecca, Saudi Arabia.
⁸ College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia.
⁹ Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.
¹⁰ Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia.
¹¹ Department of Laboratory, King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia.
¹² Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif, Saudi Arabia.
¹³ Surgery Department, College of Medicine, Al-Qunfudah Branch, Umm Al-Qura University, Mecca, Saudi Arabia.
¹⁴ Department of Human Anatomy, College of Medicine, Taif University, Taif, Saudi Arabia.
¹⁵ Cardiology Department, King Abdullah Medical Complex, Jeddah, Saudi Arabia.
¹⁶ Zoology Department, Faculty of Sciences, Sohag University, Sohag, Egypt.
¹⁷ Department of Biology, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
¹⁸ Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo, Egypt.
¹⁹ Departamento de Sanidad Animal, Grupo de Investigación en Sanidad Animal y Zoonosis (GISAZ), Facultad de Veterinaria, Universidad de Córdoba, Córdoba, Spain.
²⁰ Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag, Egypt.

^# Contributed equally.

Abstract

Background: Diabetes mellitus (DM) is a chronic metabolic disorder. Hepatopathy is one of the serious effects of DM Melatonin (MT) is a potent endogenous antioxidant that can control insulin output. However, little information is available about the potential association between melatonin and hepatic alpha-fetoprotein expression in diabetes.

Objective: This study was conducted to assess the influence of MT on diabetes-related hepatic injuries and to determine how β-cells of the pancreas in diabetic rats respond to MT administration.

Materials and methods: Forty rats were assigned to four groups at random (ten animals per group). Group I served as a normal control group. Group II was induced with DM, and a single dose of freshly prepared streptozotocin (45 mg/kg body weight) was intraperitoneally injected. In Group III, rats received 10 mg/kg/day of intraperitoneal melatonin (IP MT) intraperitoneally over a period of 4 weeks. In Group IV (DM + MT), following the induction of diabetes, rats received MT (the same as in Group III). Fasting blood sugar, glycosylated hemoglobin (HbA1c), and serum insulin levels were assessed at the end of the experimental period. Serum liver function tests were performed. The pancreas and liver were examined histopathologically and immunohistochemically for insulin and alpha-fetoprotein (AFP) antibodies, respectively.

Results: MT was found to significantly modulate the raised blood glucose, HbA1c, and insulin levels induced by diabetes, as well as the decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, MT attenuated diabetic degenerative changes in the pancreas and the hepatic histological structure, increased the β-cell percentage area, and decreased AFP expression in the liver tissue. It attenuated diabetes-induced hepatic injury by restoring pancreatic β-cells; its antioxidant effect also reduced hepatocyte injury.

Conclusion: Collectively, the present study confirmed the potential benefits of MT in downregulating the increased hepatic alpha-fetoprotein expression and in restoring pancreatic β-cells in a streptozotocin-induced diabetic rat model, suggesting its promising role in the treatment of diabetes.

Keywords: STZ; alpha-fetoprotein expression; diabetes; histopathology; liver; melatonin.

Grants and funding

The authors are grateful to the high-altitude research center at Taif University for financing this study through the Research Group; project number: 1-442-48.