Abstract
The objective of this study was to clarify the actions of 3-isobutyryl-2-isopropylpyrazol [1, 5-a] pyridine (ibudilast) on calcium (Ca) and magnesium (Mg) contents in the central nervous system (CNS), heart, liver, kidney, muscle, abdominal aorta and bone of rabbits fed cholesterol-rich diets.
Thirty male rabbits were divided into five groups. Each group was fed standard diet (group A), standard diet containing 1.0% cholesterol (group B), standard diet containing 1.0% cholesterol plus oral administration of 2.5mg/kg/day of ibudilast (group C), standard diet containing 1.0% cholesterol plus oral administration of 10mg/kg/day of ibudilast (group D) and standard diet containing 1.0% cholesterol plus oral administration of 2.5mg/kg/day of ibudilast and 300mg/kg/day of nicomol (group E). After the three months, blood was collected by cardiocentesis using ether anesthesia. The rabbits were then sacrificed to remove the CNS and other tissues. Blood was left to stand for 1 hour at room temperature and serum was separated by centrifugation of 3000rpm for 10min. to determine total cholesterol, phospholipids, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, peroxide lipid, NEFA, thromboxane B2 (TXB2) and other biochemical indices. The pathological changes in each tissue were observed. Serum TXB2 levels were decreased in groups D and E, compared with those in Group B (p<0.05). The atherosclerotic changes in groups D and E were ameliorated, in comparison with the findings of group B and C. Ca contents in the frontal cortex and cerebellum of Groups A and E and in the pons of group E were significantly lower than those of group B (p<0.05). Ca content in the cerebellum showed lower values in groups C and D than those in group (B (p<0.05). Ca content in the abdominal aorta of groups A and D, and especially of group E, were decreased, compared with those contents of Groups B and C. However, there were no significant differences in the Mg contents of the CNS and other tissues in each group.
These results suggest that higher contents of Ca in the CNS and abdominal aorta were deposited and atherosclerotic changes were observed in rabbits fed cholesterol-rich diet. Furthermore, the actions of 10mg/kg/day of ibudilast and 2.5mg/kg/day ibudilast plus 300mg/kg/day nicomol exerted a scavenger effect on Ca deposition in the CNS and abdominal aorta.
