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Cytochrome P4503A activity affects the gender difference in the development of steroid‐induced osteonecrosis in rabbits
Author(s) -
Ikemura Satoshi,
Yamamoto Takuaki,
Motomura Goro,
Yamaguchi Ryosuke,
Zhao Garida,
Iwasaki Kenyu,
Iwamoto Yukihide
Publication year - 2014
Publication title -
international journal of experimental pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.671
H-Index - 72
eISSN - 1365-2613
pISSN - 0959-9673
DOI - 10.1111/iep.12060
Subject(s) - medicine , steroid , endocrinology , cytochrome , sex steroid , biology , hormone , biochemistry , enzyme
Summary The aim of this study was to investigate cytochrome P 4503 A activity and its correlation with the development of osternecrosis (ON) among male and female steroid‐treated rabbits. Forty adult rabbits (male, n = 20; female, n = 20) were injected once with 20 mg/kg of methylprednisolone intramuscularly. Haematologically, cytochrome P 4503 A activity was measured by plasma 1′‐hydroxymidazolam‐to‐midazolam (1′‐ OH ‐ MDZ / MDZ ) ratio just before and 48 h after the steroid injection. We also measured the levels of oestradiol every week. Both femora and humeri were histopathologically examined for the presence of ON . Fifteen of 20 male rabbits (75%) developed ON , while 6 of 20 female rabbits (30%) did so. There was a significant difference in the rate of incidence of ON between male and female rabbits ( P = 0.010). The 1′‐ OH ‐ MDZ / MDZ ratio in female rabbits just before, as well as 48 h after the steroid injection was significantly higher than that in male rabbits ( P = 0.039 and P = 0.001 respectively). In addition, 1′‐ OH ‐ MDZ / MDZ ratio in female rabbits significantly increased in 48 h after the steroid injection ( P = 0.044), while that in male rabbits did not so ( P = 0.978). The levels of oestradiol in female rabbits were significantly higher than those in male rabbits during the experimental period ( P = 0.008). In conclusion, this study indicates that the gender difference in cytochrome P 4503 A activity may be one of the important factors for the development of steroid‐induced ON , possibly due to the effects of oestradiol.