Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When treating gout patients, we have incidentally found elevated serum levels of adiponectin in some after administration of benzbromarone. In the present study, we determined whether benzbromarone increases the serum level of adiponectin in gout patients and investigated the mechanism involved. Sixty-nine patients with gout were separated into two groups, and then treated for 1 year with uric acid-lowering therapy using benzbromarone or allopurinol. After overnight fasting, blood samples were drawn before and at 1 year after beginning of treatment. In an in vitro study, 3T3L1 cells were incubated in medium containing benzbromarone, allopurinol, pioglitazone, or uric acid, after which real time PCR assays were performed for messenger RNA of adiponectin, aP2, and CD36. Furthermore, 3T3L1 cells were incubated in medium containing GW9662 (PPARgamma antagonist) together with benzbromarone or pioglitazone, after which real-time PCR assays were performed for messenger RNA of adiponectin. In the in vivo study, benzbromarone increased the serum concentration of adiponectin in the subjects, whereas allopurinol did not. In vitro, benzbromarone and pioglitazone each increased the levels of messenger RNA of adiponectin, aP2, and CD36 in 3T3 cells, whereas allopurinol and uric acid did not. Also, GW9662 suppressed the increase in adiponectin mRNA induced by benzbromarone as well as that by pioglitazone. Together, our results suggest that benzbromarone enhances the production of adiponectin via activation of PPARgamma, which is a weak agonist for PPARgamma.
 ...
PMID:Effects of benzbromarone and allopurinol on adiponectin in vivo and in vitro. 1904 58

This report is the story of the long journey to identify the mechanism of fulminant hepatitis by the antigout drug, Benzbromarone. As soon as the 8th gout patient prescribed Benzbromarone (Benz) died of fulminant hepatitis in 20 years, the letter was sent to doctors identifying it as the causative agent in February 2000. At that time, Benz had been prescribed to 350,000 patients/year for 20 years. Is Benz the real cause of fulminant hepatitis? 1. Benz is a PPARa agonist like fenofibrate, and not a PPARgamma like troglitazone. 2. Troglitazone and Allopurinol have shown apoptosis in a human primary hepatocyte culture with the DNA laddering method, but Benz has not. 3. It was reported in 1979 that benzarone is a metabolite dissociated from two Br bases of Benz, but Walter et al. reported in 1987 that the Br base was not dissociated. Benzarone was not produced by an in vitro study with human S-9 and by an in vivo clinical study of Japanese volunteers. 4. The main metabolite of Benz in humans is 6-OH Benz, which has URAT-1 activity, like Benz. 5. It has been newly discovered that CYP2C9 is only one hepatic metabolism enzyme of Benz. 6. The rate of poor metabolizers of CYP2C9*3 (homozygous) in Japan is 1/2500, meanwhile, the rate of fulminant hepatitis at this time is 8 patients in 20 years, with 350,000 patients/year; therefore, it is difficult to view poor metabolizers as the cause. 7. Hepatic injury by Benz is an idiosyncrasy, the same as with many other drugs.
 ...
PMID:[Drug-induced hepatic injury, the challenge for cause investigation]. 2233 14