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L. G. Sheflin, J. E. Young, N. S. Peachey, S. J. Fliesler; Effects of Combined Antioxidant/Cholesterol Supplementation in a Rat Model of Smith-Lemli-Opitz Syndrome. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1415. doi: https://doi.org/.
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Previously we showed that feeding a diet containing 2% cholesterol (Chol) partially prevented retinal function deficits in the AY9944-induced rat model of Smith-Lemli-Opitz syndrome (SLOS) (Fliesler et al., 2007). Here, we assessed the additional benefits of dietary antioxidant (AO) supplementation in this model.
Sprague-Dawley rats were treated with AY9944 (AY) to produce the SLOS rat model (Fliesler et al., 2004); untreated age-matched rats served as controls. At weaning, SLOS rats were randomized to three dietary groups: 1) AY (normal (0% Chol) chow); 2) AC (2% (w/w) Chol chow); and 3) AO (chow containing 2% Chol and 5% (w/w) complex AO mixture). At 3 mo, rats were assessed by electroretinography (ERG); eyes were harvested for histological analysis; companion tissues (retina, serum, liver) were harvested for biochemical analyses at 3 mo as well as at earlier time points.
No significant differences in retinal structure or function were observed comparing AC vs. AO groups. While both showed similar, marked structural and functional improvements over the AY group, neither were comparable to controls. AY rats exhibited increased 4-hydroxy-2-nonenal (HNE) modification of three serum proteins: ca. 120 kDa (120%), 80 kDa (35%), and 37 kDa (55%), relative to controls (p <0.05). AC rats exhibited decreased HNE modification of these proteins (by 28%, 19% and 14%, respectively; p<0.05), as did AO rats (by 29%, 32% and 46%, respectively; p<0.05) compared to AY rats. AY rats also had decreased serum ApoE levels (by 70-90%; p<0.05), compared to controls; AC and AO rats had serum ApoE levels comparable to controls.
Under the conditions employed, while AO supplementation provided no additional beneficial effect over 2% dietary Chol supplementation alone with regard to retinal structure or function in the SLOS rat model, AO further reduced HNE modification of some serum biomarker proteins. AO may require further optimization to achieve desired beneficial effects.
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