Diane Shelton

We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6;-8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04;-0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57. 5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL.In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.

From December, 1997, through November, 2000, 306 deaths were documented among adult and subadult American alligators (Alligator mississippiensis) of Lake Griffin, Florida (USA). Some live alligators were lethargic and unresponsive to approach. To determine the cause, we examined ten alligators captured from Lake Griffin between December 1997 and June 1999. Initially, four alligators, three of which were clinically unresponsive, were sacrificed for routine diagnostic necropsy. The other six Lake Griffin alligators, and five control alligators captured from Lake Woodruff National Wildlife Refuge, Florida, where mortality was negligible, were studied extensively by clinical neurologic examination, electromyography, hematology, serum chemical analyses, and blood culture, then sacrificed and necropsied. Samples of brain, spinal cord, peripheral nerves, skeletal muscle, and major internal organs were examined by light microscopy for abnormalities. Samples of nervous tissue also were examined by electron microscopy, and samples of various tissues were collected for toxicologic analyses. Clinical signs included swimming in circles, inability to submerge, lethargy, weakness, unresponsiveness, slow reflexes, dragging the dorsal surfaces of the hind feet, head tilt, and anisocoria. Lake Griffin alligators had significantly lower distal sciatic nerve conduction velocities than Lake Woodruff alligators, and the most severely affected alligators had the lowest velocities; but morphologic abnormalities in peripheral nerves were not evident in most cases. Three severely affected alligators had acute focal necrosis of the torus semicircularis in the midbrain, two had skeletal myofiber atrophy, another had diffuse nonsuppurative encephalomyelitis, and one mildly affected alligator had skeletal myodegeneration. The cause or causes have not yet been identified.