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Effect of clarithromycin on alpha1-acid glycoprotein levels in normal and diabetic rats
T Komori1, A Nonaka, T Maruyama
1Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Abstract:
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.
Insights
Clarithromycin (CAM), an antibiotic, elevates alpha1-acid glycoprotein (AGP) serum levels dose-dependently. This AGP induction by CAM may differ from pathways triggered by phenobarbital or inflammation.
Area of Science:
- Pharmacology
- Biochemistry
- Immunology
Background:
- Alpha1-acid glycoprotein (AGP) is an acute-phase protein (APP) synthesized by the liver, with elevated serum levels during inflammation.
- Macrolide antibiotics, like clarithromycin (CAM), are widely used clinically.
Purpose of the Study:
- To investigate the effect of clarithromycin (CAM) on serum levels of alpha1-acid glycoprotein (AGP).
- To elucidate the mechanism of AGP induction by CAM and compare it with other agents and inflammatory pathways.
- To examine the modulation of AGP induction by CAM in a diabetic state.
Main Methods:
- Administration of clarithromycin (CAM), phenobarbital (PB), ethynylestradiol (EE2), and dexamethasone (DEX) to rats.
- Measurement of serum levels of AGP, alpha2-macroglobulin, and albumin.
- Examination of APP fluctuation patterns in normal and streptozotocin-induced diabetic rats.
Main Results:
- CAM treatment increased serum AGP levels in a dose-dependent manner, peaking at 48 hours.
- CAM induced lower levels of alpha2-macroglobulin compared to PB or inflammation.
- Albumin levels were unaffected by CAM but decreased during inflammation.
- AGP induction by CAM, EE2, and DEX was attenuated in diabetic rats, while PB-induced AGP increase was potentiated.
Conclusions:
- Clarithromycin (CAM) significantly increases serum AGP levels through a mechanism potentially distinct from phenobarbital (PB) and typical inflammatory pathways.
- The effect of CAM on AGP induction is modulated by the diabetic state, suggesting complex interactions.
- CAM and dexamethasone (DEX) exhibit similar patterns of APP fluctuation, hinting at shared regulatory mechanisms.