RESUMO
Acyl glucuronides (AGs) are known as one of the causes of idiosyncratic drug toxicity (IDT). Although AGs can be enzymatically hydrolysed by ß-glucuronidase and esterase, much information on their characteristics and species differences is lacking. This study was aimed to clarify species differences in AG hydrolysis between human and rat liver microsomes (HLM and RLM).To evaluate the AG hydrolysis profile, and the contribution of ß-glucuronidase and esterase towards AG hydrolysis in HLM and RLM, nonsteroidal anti-inflammatory drugs (NSAIDs) were used. AGs were incubated with 0.1 M Tris-HCl buffer (pH 7.4) and 0.3 mg/mL HLM or RLM in the absence or presence of ß-glucuronidase inhibitor, D-saccharic acid 1,4-lactone (D-SL) and esterase inhibitor, phenylmethylsulfonyl fluoride (PMSF).AGs of mefenamic acid (MEF-AG) and etodolac (ETO-AG) showed significantly higher AG hydrolysis rates in RLM than in HLM. Esterases were found to serve as AG hydrolases dominantly in HLM, whereas both esterases and ß-glucuronidase equally contribute to AG hydrolysis in RLM. However, MEF-AG and ETO-AG were hydrolysed only by ß-glucuronidase.We demonstrated for the first time that the activity of AG hydrolases towards NSAID-AGs differs between humans and rats.
Assuntos
Glucuronídeos , Microssomos Hepáticos , Humanos , Ratos , Animais , Esterases , Glucuronidase , FígadoRESUMO
The more manga (Japanese graphic novels) communicate medical information, the more people are likely to be influenced by manga. We investigated through an Internet search using Google the characteristics of medical manga published in Japan, defined as those in which the main character is a medical professional and that occur in a medical setting. As of December 2008, 173 medical manga had been published. For a period of time after the first medical manga by Osamu Tezuka in 1970, the number of publications maintained a steady level, but increased rapidly in the mid 1980s. The professions of the protagonist were 134 doctors, 19 nurses, 3 dentists, 3 medical students, and 1 nursing student. Although the main character was mostly a doctor, manga featuring paramedical professionals have increased since 1990s. Medical manga may be a powerful tool for increasing the awareness of the public regarding medicine.