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

褪黑激素通过抑制氧化应激、炎症、细胞凋亡和纤维化减轻顺铂诱导的颌下腺损伤

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作者: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

Background

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

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.

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.

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