This study was performed to assess the local irritation of LB00014 (EPO, erythropoietin) at the different injection sites, muscle and ear vein of rabbit.
To examine the induction of irritation at the muscle, two groups of rabbits(6 animals/group), were treated with 0.5ml/rabbit/day of LB00014-L (의원,000 IU/ml), LB00014-H (10,000 IU/ml) and the other group injected with acetic acid(0.75%) was used
as a
positive control. LB00014 and acetic acid were injected at the right side of biceps femoris muscle for 7 days, while left sides were treated with the Phosphate Buffed Saline, PBS(contains 0.25% Human Serum Allbumin, HAS) as a negative control.
For
the
gross and histopathologic examination, rabbits were killed at 대학교 and 7 days after injection.
Gross and histopathologic changes caused by LB00014-L and LB00014-H were comparable to that caused by PBS at 대학교 days after injection, but changes caused by acetic acid were severer than the other groups. 7 days after injection, the sites
injected
with PBS, LB00014-L and LB00014-H showed normal appearance, but the lesions were still presented at the acetic acid injected sites.
To examine vascular changes, two groups of rabbits(대학교 의과대학 animals/group) were injected with 0.025ml/rabbit/bid of the LB00014-L, LB00014-H and group 대학교 의과대학 injected with sulfobromophthalein sodium (BSP, 의원%) was used as a
positive
control . The test materials were injected on the right sides of ear veins, for 8 days, twice a day with 6 hour interval. The left sides were injected with the PBS(contains 0.25% HAS) as a negative control. After treatment, animals in groups of
LB00014-L, LB00014-H and PBS(contains 0.25% HAS) injection showed induration and scar formation at the injection sites macroscopically, but the lesions produced at animals treated with 의원% BSA were severer than the other groups.
Histopathological
findings of vascular wall were comparable among LB00014-L, LB00014-H and PBS injected blood vessels. Thrombus formation with edema, mononuclear cell infiltration and mild necrosis of surrounding tissue were important change in these groups of
animals,
but vessel wall injuries with infarction or thrombus were found at the BSP injected vessels. In addition, broad area necrosis with several kinds of cell infiltration were observed in the perivascular region.
It was concluded from this study that LB00014 have the same degree of irritancy with PBS vehicle at the injected sites of muscle and blood vessel.
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