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Per Soderberg, Konstantin Galichanin, Martin Kronschlager, Zhaohua Yu, Nooshin TalebiZadeh; Alpha-tocopherol protection against UVR induced cataract, estimation of confidence interval for MTD-2.3:16 and comparison of MTD-2.3:16 estimates. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2977. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
To develop a strategy for estimation of confidence interval for Maximum Tolerable Dose-2.3:16 (MTD-2.3:16) and for confidence interval for the difference between two different MTD-2.3:16:s and to apply these strategies on Vitamin-E protection against UVR induced cataract.
Two groups of 20 animals were used, one orally supplemented with alpha-tocopherol, 100 IU, daily for 4 weeks prior to exposure to UVR and the other without supplementation. After supplementation, each group was subdivided into 5 subgroups of 4 rats. Each rat was unilaterally exposed in vivo to UVR, 0.0, 2.6, 3.7, 4.5 and 5.2 kJ/m2 depending on the subgroup belonging. The intensity of forward light scattering was measured at 1 week after exposure. The threshold dose for UVR-induced cataract was estimated as MTD2.3:16 for each of the groups. Confidence intervals for MTD-2.3:16 were derived by inverse prediction of the confidence interval for the dose corresponding to the light scattering induced at MTD-2.3:16. Comparison of the MTD-2.3:16 estimates with and without alpha-tocopherol was achieved by deriving an expression for the confidence interval for the difference between the regression coefficients with and without alpha-tocopherol, respectively.
Alpha-tocopherol protects against in vivo UVR-induced cataract (CI(0.95) for MTD-2.3:16: [2.16;3.15] kJ/m2, d.f.=19, without alpha-tocopherol supplementation and [2.41;3.67] kJ/m2, d.f = 18, with supplementation. The difference of the slopes of the dose-response function for UVR induced cataract was expressed as CI(0.95) 4.74 +/- 4.58 m tEDC m^2/kJ. The PF was estimated to 1.14, thus indicating that for animals exposed in vivo to the same irradiance, alpha-tocopherol supplementation allows 1.14 times longer exposure before cataract develops.
Alpha-tocopherol protects against oxidative stress induced by in vivo exposure to UVR-300 nm radiation. The precision of an MTD-2.3:16 estimate can now be expressed as a confidence interval. Two different estimates of MTD-2.3:16 can be statistically compared as a confidence interval for the difference between the slopes of the UVR-dose response functions. PF allows objective quantitative comparison among protective factors on in vivo effects against toxic agents such as oxidative stress induced by UVR.
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