Complete lecithin:cholesterol acyltransferase (LCAT) deficiency is a rare cause of severe hypoalphalipoproteinemia, but the affected subjects are surprisingly not particularly prone to premature coronary heart disease. We studied oxidative stress in lcat-/- mice and their cross-breed with apolipoprotein-E knockout mice (apoE-/-xlcat-/-) by measuring vascular ring superoxide production and plasma phospholipid (PL)-bound F2-isoprostane levels and their relationship with aortic atherosclerosis. Compared with wild type control (lcat+/+), lcat-/- and lcat+/- mice showed a 4.9- (p = 0.003) and a 2.1-fold (p = 0.04) increase in plasma PL-F2-isoprostane levels, respectively. There was also a 3.6- (p < 0.0001) and 2.9-fold (p = 0.003) increase in the area under the curve for the aortic ring superoxide excursion by lucigenin-derived chemiluminescence. A comparison of apoE-/-xlcat+/+ mice with wild type control mice showed a more modest 2.1- (p = 0.04) and 2.2-fold (p < 0.00001) increase in these respective markers. Surprisingly, the apoE-/-xlcat-/- mice showed a paradoxical normalization in both oxidation markers. Furthermore, by fast protein liquid chromatography separation, we observed an associated retention and redistribution of serum paraoxonase activities to the non-high density lipoprotein fractions in both the apoE-/-xlcat-/- and apoE-/-xlcat+/- mice. Aortic atherosclerotic lesions in male apoE-/-xlcat-/- and apoE-/-xlcat+/- mice were reduced by 52 (p = 0.02) and 24% (p = 0.46), respectively. Our data suggest that LCAT-deficient mice are associated with an increased oxidative stress that is paradoxically reversed in a hyperlipidemic background, possibly due to the redistribution of paraoxonase. This modulation of oxidative stress may in part contribute to the reduced atherosclerosis seen in the apoE-/- xlcat-/- mice.

Romney ewes grazed pasture initially containing 0 (C), 30 (M), or 60% (P) Pawera red clover for c. 6 months per year (spring-autumn) during the first 4 (P) or 5 (M) years of a 6-year study. When not grazing red clover, all animals grazed C-type pastures. In Years 3-6, ewes were scored on a subjective 0-3 scale for vaginal abnormalities. More of the animals grazing M pasture scored 1 or higher each year compared to the ewes on C pasture (P < 0.001). Similarly, more of the ewes grazing P herbage were scored 2 or higher than either of the other two groups (P < 0.001). A greater proportion of the ewes on the P sward were mated more than once at each joining, compared with the other two groups (P < 0.01 in Year 3; P < 0.001 in all other years) and consequently there were differences in the mean number of times each ewe was mated. Long-term grazing of oestrogenic red clover results in both a high incidence of abnormalities of the external genitalia and decreased mating performance in ewes. However, these effects appear to be independent of each other. A93026