Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of t...Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle （V）, methanesulfonic acid sodium salt （D）, light damage model plus vehicle （MV） and light damage model plus methanesulfonic acid sodium salt （MD） groups （n=25 each）. In the MD group, methanesulfonic acid sodium salt （100 mg/kg） was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy （TEM） were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography （ERG） test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c （CytC） and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group （P 〈0.05）. TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 （Apaf-1）, caspase 3, p53, p53-upregulated modulator of apoptosis （PUMA）, Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.展开更多
文摘Background Methanesulfonic acid sodium salt （Dipyrone）, an antipyretic and analgesic drug, has been demonstrated to improve cerebral ischemia through the inhibition of mitochondrial cell death cascades. The aim of this study was to evaluate the potential photoprotective activity of methanesulfonic acid sodium salt in a model of light-induced retinopathy. Methods One hundred mice were assigned randomly into vehicle （V）, methanesulfonic acid sodium salt （D）, light damage model plus vehicle （MV） and light damage model plus methanesulfonic acid sodium salt （MD） groups （n=25 each）. In the MD group, methanesulfonic acid sodium salt （100 mg/kg） was administered by intraperitoneal injection 30 minutes before light exposure. Twenty-four hours after light exposure, hematoxylin and eosin staining and transmission electron microscopy （TEM） were used for histological evaluation. The thickness of the outer plus inner-segment and outer nuclear layer was measured on sections parallel to the vertical meridian of the eye at a distance of 1000 I^m from the optic nerve. Electroretinography （ERG） test was performed to assess the functional change. The morphology of mitochondria was also revealed by TEM. Finally, the expression of cytochrome c （CytC） and the relative apoptotic proteins were detected by Western blotting, and the interaction between mitochondrial proteins was investigated by co-immunoprecipitation. Results The photoreceptor inner and outer segments of the MV group were significantly disorganized than the MD group. The thicknesses of the outer plus inner-segment layers and the outer nuclear layer, and the amplitudes of the a and b waves of the scotopic ERG response markedly decreased in the MV group compared to those in the MD group （P 〈0.05）. TEM examination revealed that the mitochondria of the MV group were distinctly swollen and contained disrupted cristae. In contrast, the morphology of mitochondria in the MD group was unaffected. Western blotting analysis showed that CytC, apoptosis proteinase activating factor-1 （Apaf-1）, caspase 3, p53, p53-upregulated modulator of apoptosis （PUMA）, Bax, and Bad were increased, whereas the anti-apoptotic proteins Bcl-2 and Bcl-XL were significantly decreased in the MV group than the MD group. Co-immunoprecipitation detection revealed that PUMA immunoreactivity precipitated by Bcl-XL decreased, whereas Bax immunoreactivity precipitated by Bcl-XL increased in the MD group compared to those in the MV group. Conclusion Methanesulfonic acid sodium salt is an effective photoprotective agent against light-induced retinopathy through the inhibition of CytC-mediated mitochondrial impairment.
