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Background <p>Radiotherapy-induced parotid gland injury is a major contributor to salivary hypofunction and xerostomia in head-and-neck cancer management. This study aimed to evaluate the differential radiobiological effects of <i>flattening filter</i> (FF) and <i>flattening filter-free</i> (FFF) 6 MV photon beams, delivered as single-dose or fractionated-dose regimens, on apoptotic, inflammatory, and angiogenic gene expression in rat parotid tissue, and to assess the potential radioprotective action of melatonin.</p> Methods <p>Female Sprague–Dawley rats (8–10 weeks old) were randomized into ten groups and irradiated with either a single 16&#xa0;Gy dose or a fractionated-dose protocol (6.4&#xa0;Gy × 5) using FF or FFF beams. Melatonin (10&#xa0;mg/kg, intraperitoneally) was administered 15&#xa0;min before irradiation. Parotid glands were collected 10 days post-irradiation, and mRNA expression levels of <i>Bax</i>,<i> Bid</i>,<i> Casp3</i>,<i> Bcl2</i>,<i> Bcl2l1</i>,<i> Il1b</i>,<i> Tnf</i>, and <i>Vegfa</i> were quantified by RT-qPCR.</p> Results <p>Irradiation significantly upregulated pro-apoptotic (<i>Bax</i>,<i> Bid</i>,<i> Casp3</i>) and pro-inflammatory (<i>Il1b</i>,<i> Tnf</i>) transcripts, along with <i>Vegfa</i>, while downregulating anti-apoptotic markers (<i>Bcl2</i>,<i> Bcl2l1</i>). These molecular alterations were more pronounced following FFF-beam and fractionated-dose. Melatonin pretreatment markedly attenuated radiation-induced gene expression changes, restored <i>Bcl2 and Bcl2l1</i> levels, and normalized the <i>Bcl2/Bcl2l1</i> ratio.</p> Conclusion <p>Melatonin effectively mitigates key apoptotic, inflammatory, and angiogenic responses associated with radiation-induced parotid gland injury. These findings support melatonin as a potential radioprotective adjunct during head-and-neck irradiation.</p>

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Ameliorative effects of melatonin on radiotherapy-induced apoptotic and inflammatory responses in rat parotid gland

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月24日

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  • Fatih Hacımustafaoğlu,
  • Serhat Aras,
  • Yalçın Erzurumlu,
  • Burcu Çaykara Peran

摘要

Background

Radiotherapy-induced parotid gland injury is a major contributor to salivary hypofunction and xerostomia in head-and-neck cancer management. This study aimed to evaluate the differential radiobiological effects of flattening filter (FF) and flattening filter-free (FFF) 6 MV photon beams, delivered as single-dose or fractionated-dose regimens, on apoptotic, inflammatory, and angiogenic gene expression in rat parotid tissue, and to assess the potential radioprotective action of melatonin.

Methods

Female Sprague–Dawley rats (8–10 weeks old) were randomized into ten groups and irradiated with either a single 16 Gy dose or a fractionated-dose protocol (6.4 Gy × 5) using FF or FFF beams. Melatonin (10 mg/kg, intraperitoneally) was administered 15 min before irradiation. Parotid glands were collected 10 days post-irradiation, and mRNA expression levels of Bax, Bid, Casp3, Bcl2, Bcl2l1, Il1b, Tnf, and Vegfa were quantified by RT-qPCR.

Results

Irradiation significantly upregulated pro-apoptotic (Bax, Bid, Casp3) and pro-inflammatory (Il1b, Tnf) transcripts, along with Vegfa, while downregulating anti-apoptotic markers (Bcl2, Bcl2l1). These molecular alterations were more pronounced following FFF-beam and fractionated-dose. Melatonin pretreatment markedly attenuated radiation-induced gene expression changes, restored Bcl2 and Bcl2l1 levels, and normalized the Bcl2/Bcl2l1 ratio.

Conclusion

Melatonin effectively mitigates key apoptotic, inflammatory, and angiogenic responses associated with radiation-induced parotid gland injury. These findings support melatonin as a potential radioprotective adjunct during head-and-neck irradiation.