Effect of clarithromycin on alpha1-acid glycoprotein levels in normal and diabetic rats.
The elevation of alpha1-acid glycoprotein (AGP) serum level, a member of the acute phase proteins (APP) synthesized by the liver, is induced during inflammation. In this study, we show that clarithromycin (CAM), a 14-membered macrolide antibiotic, causes an increase in the serum levels of AGP in a dose-dependent manner. AGP levels peak at 48h after a single administration with CAM In order to elucidate the mechanism of AGP induction by CAM, the effects of CAM, phenobarbital (PB), ethynylestradiol (EE2) and dexamethasone (DEX) treatments on APP fluctuation patterns were examined. In addition, modulation of the AGP induction by CAM, PB, EE2 and DEX in the diabetic state was examined. In contrast to treatment by PB, CAM treatment increased alpha2-macroglobulin levels to a much lesser extent than that observed during inflammation. On the other hand, albumin levels were unaffected by CAM treatment but decreased during inflammation. In addition, AGP induction by CAM, EE2 and DEX were attenuated in streptozotocin-induced diabetic rats, whereas the PB-induced increase in AGP levels was potentiated in diabetic rats. Thus, CAM and DEX treatments appear to induce similar fluctuations in APP levels. These results suggest that CAM increases AGP levels via a mechanism which may be different from PB and typical inflammatory pathways.
Komori
T
T
Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Nonaka
A
A
Maruyama
T
T
Otagiri
M
M
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D017291:Clarithromycin / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D009961:Orosomucoid / Q000187:drug effects* / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D006993:Hypnotics and Sedatives; D009961:Orosomucoid; D003907:Dexamethasone; D017291:Clarithromycin; D010634:Phenobarbital