The effects of heparan sulphate mimetic RGTA-OTR4120 on irradiated murine salivary glands

Background: This study focuses on the potential of ReGeneraTing Agent OTR4120 (RGTA-OTR4120) to treat radiation-induced damage of salivary glands. RGTAs are biopolymers designed to mimic the effects of heparan sulphate, thereby stimulation tissue repair and regeneration. Methods: C3H mice were irradiated with a single dose of 15Gy in the head and neck region. RGTA-OTR4120 was injected 24h after radiotherapy, followed by weekly injections. At 2, 6 and 10weeks after radiotherapy, salivary flow rates were measured and animals were sacrificed to obtain parotid and submandibular glands for histology. Periodic acid Schiff stain was performed to visualize mucins that are produced by acinar cells. Amylase and total protein content were measured in saliva samples. Results: Salivary flow rates were increased at 2weeks, but not at 6 and 10weeks after radiotherapy with RGTA-OTR4120 administration, compared to irradiated controls. Two and 10weeks after radiotherapy, the mucin production activity of acinar cells was increased under influence of RGTA administration. RGTA-OTR4120 did not influence amylase or total protein secretion. Conclusion: RGTA-OTR4120 administration has a positive effect on salivary flow rates in irradiated mice on the short term. The effect was absent 10weeks after radiotherapy, while at that time point, mucin producing activity of acinar cells was elevated by RGTA-OTR4120 administration. Given these results and the advantages of RGTA use in irradiated patients, further investigation on the potential of this drug to treat radiation-induced salivary gland damage, alone or in combination with other drugs, such as amifostine, is suggested.

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