Abstract
In Chronic Renal Failure (CRF) patients, the hepatic clearance of many drugs is altered, which could be due to downregulation of hepatic enzymes. UGT1A6 is an important Phase II enzyme involved in the glucuronidation of planar phenols. The purpose of this study was to determine the catalytic activity and protein levels of rat hepatic and renal UGT1A6. CRF was induced in male Sprague-Dawley rats (n=4) by 5/6th Nephrectomy model in which two-thirds of left kidney and complete right kidney were excised and animals were sacrificed after 5 weeks; control animals (n=5) were sham operated and pair fed. UGT1A6 activity was determined by the glucuronidation of 4-methylumbelliferone (4MU) and Vmax and Km values were determined for hepatic UGT1A6. Protein content of UGT1A6 was examined by Western blot using a polyclonal antibody. There was no difference between CRF and CPF rats in hepatic and renal 4MU UGT activity (CRF liver: 32.08±4.82 nmole/min/mg, CPF liver: 30.26±5.54 nmole/min/mg; CRF kidney: 14.30±5.04 nmole/min/mg, CPF kidney: 13.63±5.55 nmole/min/mg) and UGT1A6 protein level. No difference was observed in the Vmax and Km values between the two groups. UGT1A6 protein levels were similar between the liver and the kidney. However the UGT1A6 activity was ~2-fold higher in the liver than the kidney, suggesting that 4MU may also be metabolized by other UGT isozymes in liver. CRF does not appear to influence the protein levels or catalytic activity of UGT1A6. Clinical Pharmacology & Therapeutics (2004) 75, P86–P86; doi: 10.1016/j.clpt.2003.11.327
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