Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis

Alaa M Badawy; Mohie Ibrahim; Medhat Taha; Azza I Helal; Ahmed Abdel-Monem Elmetwally; Ibrahim El-Shenbaby; Sara Abubakr; Emadeldeen Hussin; Noha Hammad Sakr; Tourki A S Baokbah; Amira E Farage

doi:10.7759/cureus.68515

Melatonin Mitigates Cisplatin-Induced Submandibular Gland Damage by Inhibiting Oxidative Stress, Inflammation, Apoptosis, and Fibrosis

Cureus. 2024 Sep 3;16(9):e68515. doi: 10.7759/cureus.68515. eCollection 2024 Sep.

Authors

Affiliations

¹ Department of Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, EGY.
² Department of Basic Medical and Dental Sciences, Faculty of Dentistry, Zarqaa University, Zarqa, JOR.
³ Department of Anatomy, Umm Al-Qura University, Al-Qunfudhah, SAU.
⁴ Department of Histology and Cell Biology, Faculty of Medicine, Kafrelsheikh University, Kafr El Sheikh, EGY.
⁵ Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, EGY.
⁶ Department of Anatomy and Embryology, Faculty of Medicine, Kafrelsheikh University, Kafr El Sheikh, EGY.
⁷ Department of Medical Emergency Services, Umm Al-Qura University, Al-Qunfudhah, SAU.

Abstract

Background: The study aims to examine the possible effect of melatonin against cisplatin-induced submandibular degeneration in experimental rats exploring its ameliorative mechanisms.

Methods: Rats were classified into four experimental groups; control group; melatonin group; cisplatin group; and cisplatin+melatonin group. Submandibular tissues were collected. Biochemical, histopathological, and immunohistopathological examination and quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis were performed.

Results: The results indicate that intraperitoneal administration of melatonin (30 mg/kg body weight) alongside cisplatin significantly elevated submandibular glands (SMG) and reduced glutathione (GSH) and superoxide dismutase (SOD) levels (p < 0.001), while it reduced malondialdehyde (MDA) levels, NF-κB gene expression, the protein level of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1 beta (IL-1β), immunoexpression of low-dose cyclooxygenase-2 (Cox-2), and CD68. Moreover, melatonin reduced immune and gene expression of alpha-smooth muscle actin (α-SMA), immunoexpression of caspase-3, and gene expression of Bax in comparison to the cisplatin group.

Conclusion: Melatonin attenuated cisplatin-induced submandibular destruction alleviating SMG oxidative stress, inflammation, and fibrosis in addition to halting cellular apoptosis, sheds light on its usage in clinical application.

Keywords: apoptosis; cisplatin; fibrosis; inflammation; melatonin; oxidative stress; submandibular gland.