International journal of radiation biology · 2024
Valproic acid alleviates total-body irradiation-induced small intestinal mucositis in mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Kurokawa Yukiro, Watanabe Shinichi, Yano Takaaki, Izumi Tomoki, Hidaka Noriaki, Yamaguchi Takumi, Tanaka Mamoru
Аннотация
PURPOSE: Gastrointestinal (GI) injury is one of the serious problems of total-body irradiation (TBI). However, no fundamental treatment for TBI and other radiation-induced GI injury has yet been established. Valproic acid (VPA) administration reduces mortality in mice subjected to total-body irradiation (TBI) with X-rays. This study aimed to evaluate the effects of VPA on GI injury induced by TBI in mice.
MATERIALS AND METHODS: Mice were subjected to TBI with X-rays to induce GI injury. Changes in survival and weight were observed after VPA administration. The small intestine was then sampled at 0, 1, 3, 7, and 10 d after irradiation for histological and immunohistological evaluation and measurement of myeloperoxidase (MPO) activity and inflammatory cytokine levels (IL-1β).
RESULTS: VPA (200 and 600 mg/kg) increased survival rate and reduced weight loss in model mice. IL-1β expression 1 d after irradiation was significantly lower in the VPA group than that in the vehicle group. Furthermore, the increase in MPO activity at 3 and 7 d after irradiation was significantly suppressed by VPA administration. Histological examination (hematoxylin and eosin staining) revealed that 600 mg/kg VPA inhibited inflammatory cell infiltration. Immunostaining for the proliferating cell nuclear antigen involved in cell proliferation showed that VPA suppressed the irradiation-induced decrease in cell proliferative capacity.
CONCLUSIONS: Treatment with VPA in mice with GI injury caused by TBI suppressed inflammatory responses in small intestinal mucosal cells. These results suggest that VPA may be a useful therapeutic agent against TBI-induced small intestinal mucositis.
MATERIALS AND METHODS: Mice were subjected to TBI with X-rays to induce GI injury. Changes in survival and weight were observed after VPA administration. The small intestine was then sampled at 0, 1, 3, 7, and 10 d after irradiation for histological and immunohistological evaluation and measurement of myeloperoxidase (MPO) activity and inflammatory cytokine levels (IL-1β).
RESULTS: VPA (200 and 600 mg/kg) increased survival rate and reduced weight loss in model mice. IL-1β expression 1 d after irradiation was significantly lower in the VPA group than that in the vehicle group. Furthermore, the increase in MPO activity at 3 and 7 d after irradiation was significantly suppressed by VPA administration. Histological examination (hematoxylin and eosin staining) revealed that 600 mg/kg VPA inhibited inflammatory cell infiltration. Immunostaining for the proliferating cell nuclear antigen involved in cell proliferation showed that VPA suppressed the irradiation-induced decrease in cell proliferative capacity.
CONCLUSIONS: Treatment with VPA in mice with GI injury caused by TBI suppressed inflammatory responses in small intestinal mucosal cells. These results suggest that VPA may be a useful therapeutic agent against TBI-induced small intestinal mucositis.