Cytoprotective effects of opioids on irradiated oral epithelial cells

Oral mucositis is a common side effect of chemotherapy and radiation therapy accompanied with acute inflammation and ulceration of the oral mucosa. Opioids can improve the wound healing of dermal and oral tissue when applied locally. The aim of this study was to investigate if morphine exhibits cytoprotective effects on oral epithelial cells postirradiation. Hence, oral epithelial cells were exposed to increasing doses (3-30 Gy) of ionization radiation. We assessed the effects of the radiation on cell viability, proinflammatory cytokine release (interleukin [IL]-1α, IL-6), and matrix metalloproteinase (MMP-1, -8, and -9) expression. As expected, radiation significantly impaired cell viability and morphology and resulted in enhanced IL release. However, morphine-treated cells consistently showed higher cell viability postirradiation: 9.19 ± 1.16% after 24 hours and 7.45 ± 0.93% after 48 hours compared with the control. In terms of proinflammatory cytokines, the release of IL-1α and IL-6 was significantly reduced, too, being most pronounced at 48 hours postradiation. Additionally, we observed a significant reduction of MMP-1 and especially MMP-9 expression in morphine-treated cells. The results clearly indicate anti-inflammatory as well as cytoprotective effects of morphine on irradiated oral epithelial cells. Interestingly, the protective effects of morphine are not related to a decrease in cell apoptosis or necrosis. Before final conclusions can be drawn, further studies in more complex systems in vitro and in vivo are required. Nevertheless, these findings further underline the high potential of opioids for the treatment of topical wounds and inflammatory conditions.