| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Research Abstract |
The aim of this study is to evaluate the effect of anastrozole (ANA), a new generation aromatase inhibitor, on lipid metabolism, especially lipoprotein lipase (LPL) activity, compared with selective estrogen receptor modulators (SERMs) in rats. We previously reported that tamoxifen (TAM), one of SERMs, decreases the activity of LPL, a key enzyme of triglyceride metabolism, in clinical and experimental studies. Ovariectomized female rats were divided into six groups : C, controls ; TAM, tamoxifen treatment ; TOR, toremifene treatment ; ANA, anastrozole treatment ; CAT, combined anastrozole/tamoxifen treatment ; and AAT, anastrozle treatment after tamoxifen. The agents were orally administered for three weeks. Serum total cholesterol, triglycerides, and LPL activity in post-heparin plasma were measured at the end of the experiment.
Serum cholesterol levels were significantly lower in the TAM, TOR and CAT groups than in controls (P<0.001). Serum triglyceride levels were significantly higher in the TAM group than in the other groups (P<O.001). LPL activity was significantly lower in TAM and AAT groups (P<0.01). There was no significant difference in any other parameters in group ANA. ANA does not affect lipid metabolism including LPL activity. There was little effect on lipid profiles during combination treatment or following treatment with TAM. In clinical situation, therefore, ANA might be safe for patients with abnormal triglyceride profiles during SERMs treatment.
Moreover, exemestane (EXE), a new aromatase inactivator, has been in clinical situation since 2002 and we also investigated the effect of this agent on VLDL metabolis mcompared with ANA. It is indicated that EXE has a beneficial effect for VLDL metabolism because of the increment of LPL mass.
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