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Per G. Soderberg, Jing Xiao, Jing Wang, Konstantin Galichanin, Martin Kronschläger, Zhaohua Yu, Nooshin Talebizadeh, Joakim Ekström; 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. 2012;53(14):2283.
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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.
Altogether, 40 albino Sprague Dawley rats were divided into one group of 20 animals orally supplemented with α-tocopherol, 100 IU daily for 4 weeks prior to exposure to UVR and another group of 20 animals without supplementation. Each group, then was subdivided into 5 subgroups of 4 rats. Each rat was unilaterally exposed in vivo to UVR, with a dose of UVR depending on the subgroup belonging. The subgroup doses were 0.0, 2.6, 3.7, 4.5 and 5.2 kJ/m2 UVR-300 nm for 15 min, respectively. At 1 week after exposure to UVR, the rat was sacrificed and the lenses were extracted, The intensity of forward light scattering was measured. 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. The protection factor (PF) for alpha-tocopherol is the ratio between MTD-2.3:16 with supplementation and MTD-2.3:16 without supplementation.
Alpha-tocopherol protected against in vivo UVR-induced cataract. The 95 % confidence interval for MTD-2.3:16 was estimated to [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 95 % confidence interval for the difference of the slopes of the dose-response function for UVR induced cataract was 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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