Differential expression of hepatic UDP-Glucuronosyltransferase during dietary magnesium depletion

Abstract

Male Sprague Dawley rats weighing 80±5 g were fed either a magnesium deficient (MgD) diet (30, 66 or 85 mg/kg) or a pair-fed control (PFC) diet (595 mg/kg) for 10 days. Serum Mg +2 was decreased 66% in the magnesium depleted animals (on diets of 30 and 66 mg of Mg +2/kg), no significant change was noted for total liver magnesium concentration. Hepatic microsmes were prepared and used fresh or stored at −70°C. The total UDP-glucuronosyl-transferase (UDP-GT) activities were evaluated using microsomes activated with Triton X-100. Three isoenzyme activities of UDP-GT were determined for specific substrates: p-nitrophenol (pNP), bilirubin (BR) and lithocholate (LiC). Addition of magnesium (10 mM) to the in vitro reaction system increased each isoenzyme activity, pNP UDP-GT (100%), BR UDP-GT (350%) and LiC UDP-GT (100%). The specific effect of dietary magnesium depletion was a decrease in pNP UDP-GT activity while the BR UDP-GT and LiC UDP-GT isoenzyme activites were not significantly changed. Below a dietary intake of about 2 mg of magnesium/day, the loss of pNP UDP-GT isoenzyme activity was proportional to the decrease in dietary Mg +2 intake. Thus, expression of the pNP UDP-GT was specifically diminished at early stages of magnesium depletion. The mechanism of this selective Mg +2 effect is under further investigation.