Reduced antioxidant and anti-inflammatory effects of propofol at high-dose on morbidly obese patients.

This study was aimed to investigate differences in antioxidant and anti-inflammatory effects of propofol at two commonly used dosing schedules on morbidly obese patients. Twenty-two morbidly obese patients were randomly divided into two groups, namely, TBW (dosing based on total body weight) and LBW (dosing based on lean body weight) groups. Three biomarkers, i.e. superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were measured as indicators of the level of oxidation stress reaction. Pro-inflammatory cytokines including Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were used to describe the degree of inflammation. Plasma levels of SOD, MDA and NO were increased and reached a peak value 0.5h after anesthesia induction, but the increase was smaller in the LBW group compared with the TBW group. Besides, plasma concentrations of IL-6 and IL-8 were also increased and attained a peak level 0.5h after anesthesia induction, but the increase was higher in the TBW group compared with the LBW group. The LBW-based dosing of propofol had more potent antioxidant and anti-inflammatory effects than the TBW-based dosing during anesthesia induction period on morbidly obese patients. This study provided a dosing recommendation of propofol for morbidly obese patients.

Regioselective glucuronidation of gingerols by human liver microsomes and expressed UDP-glucuronosyltransferase enzymes: reaction kinetics and activity correlation analyses for UGT1A9 and UGT2B7.

OBJECTIVES: To determine the reaction kinetics for regioselective glucuronidation of gingerols (i.e. 6-, 8- and 10-gingerol) by human liver microsomes and expressed UDP-glucuronosyltransferase (UGT) enzymes, and to identify the main UGT enzymes involved in regioselective glucuronidation of gingerols. METHODS: The rates of glucuronidation were determined by incubating the gingerols with uridine diphosphoglucuronic acid-supplemented microsomes. Kinetic parameters were derived by fitting an appropriate model to the data. Activity correlation analyses were performed to identify the main UGT enzymes contributing to hepatic metabolism of gingerols. KEY FINDINGS: Glucuronidation at the 4'-OH group was much more favoured than that at 5-OH. The degree of position preference was compound-dependent; the catalytic efficiency ratios of 4'-O- to 5-O-glucuronidation were 9.1, 19.7 and 2.9 for 6-, 8- and 10-gingerol, respectively. UGT1A8 (an intestinal enzyme), UGT1A9 and UGT2B7 were the enzymes showing the highest activity towards gingerols. Formation of 5-O-glucuronide was mainly catalysed by UGT1A9. UGT2B7 was the only enzyme that generated glucuronides at both 4'-OH and 5-OH sites, although a strong position preference was observed with 4'-OH (≥80.2%). Further, activity correlation analyses indicated that UGT2B7 and UGT1A9 were primarily responsible for 4'-O-glucuronidation and 5-O-glucuronidation of gingerols in the liver, respectively. CONCLUSIONS: Gingerols were metabolized by multiple hepatic and gastrointestinal UGT enzymes. Also, UGT1A9 and 2B7 were the main contributors to regioselective glucuronidation of gingerols in the liver.