Inhibitory effect of tetracyclines on pancreatic lipase activity

Abstract

To demonstrate the inhibitory potencies of 4 chemical derivatives of tetracyclines consist of tetracycline, doxycycline, chlortetracycline and oxytetracycline. Tetracyclines are a group of broad-spectrum agents, exhibiting activity against a wide range of gram-positive and gram-negative bacteria. The results showed inhibitory potency of doxycycline (IC[subscript 50] = 55.42 +- 1.67 µM) > chlortetracycline (IC[subscript 50] = 88.71 +- 11.39 µM) > tetracycline (IC[subscript 50] > 500 µM) but it had no inhibitory activity of oxytetracycline. However, the study which compared the potency between doxycycline and orlistat, a drug clinically used for weight loss by directly inhibit pancreatic lipase indicated that doxycycline was about 80 times less potent than orlistat (IC[subscript 50] = 1.31 +- 0.13 µM). The study inhibitions mechanism using Lineweaver-Burk plot showed that doxycycline was a reversible non-competitive type inhibition against pancreatic lipase which is differs from orlistat in which it was irreversible inhibition. The affinity inhibitor constant of doxycycline showed K[subscript i] = 66.41 +- 3.27 µM and K[subscript i]' = 70.49 +- 7.11 µM. Moreover, doxycycline exhibited the synergistic inhibition on pancreatic lipase activity when administration with a low dose of orlistat. The oral administration of doxycycline (20-100 mg/kg) significantly decreased serum triglyceride concentration in lipid emulsion-induced hyperlipidemia rats. In conclusion, doxycycline markedly decreased serum triglyceride concentration in rats by inhibiting pancreatic lipase. This research may be beneficial for further studies in clinical pharmacology and toxicology.