Furazolidone induces the activity of microsomal enzymes that metabolize furazolidone in chickens

Abstract

The nitrofuran antibacterial agent furazolidone (FZ) is still used in veterinary medicine in some countries in the Middle and Far East. The present study aimed to show the effect of FZ on the activity of microsomal enzymes that metabolize FZ, and to identify the enzyme that contributes to FZ metabolism in chickens. Wistar rats and White Leghorn chickens were administered FZ once a day for 4 consecutive days. FZ metabolism was accelerated by FZ administration in chickens, but not in rats. The elevation of FZ metabolism coincided with the induction of NADPH cytochrome P450 reductase (CPR) activity in chickens, but such induction was not observed in rats. FZ metabolizing activities were inhibited in the presence of a CPR inhibitor (diphenylene iodonium chloride) but not by the addition of archetypal cytochrome P450 inhibitors (CO or n-octylamine). The preset study concluded that FZ accelerated its own metabolism in the chicken by induction of the activity of CPR.

Repeated Treatment with Furazolidone Induces Multiple Cytochrome P450-Related Activities in Chicken Liver, but Not in Rat Liver

“…Liver microsomes were prepared according to the method of Omura and Sato [25] and the procedure of the preparation followed those described in a previous report [31]. The protein concentration of the microsome fraction was determined by the method of Lowry et al .…”

“…Treatment with FZ (0.04%, for 10 days) in feed caused a decrease in the duration of barbital anesthesia, but had no such effect when administered as a bolus dose of 200 mg/kg FZ [ 5 ]. Recently, we have demonstrated that FZ treatment in chickens induced facilitation of its metabolic rate that was dependent on increased activity of NADPH cytochrome P450 reductase in the liver [ 31 ].…”

“…All the animals were maintained at 23°C in a 12-hr dark/light cycle starting at 07:00 hr. In this study, the FZ dosages and animals followed those described in the previous report [ 31 ]. The following treatment groups each consisted of 3 rats and 3 chickens: FZ (125 mg/kg/day given orally for 4 days), FZ (62.5 mg/kg/day given orally for 4 days), AOZ (57 mg/kg/day equivalent to FZ 125 mg/kg/day given intraperitoneally for 4 days), HEH (42 mg/kg/day equivalent to FZ 125 mg/kg given intraperitoneally for 4 days) and 2% aqueous acacia solution (5 m l /kg/day given orally for 4 days) as a control.…”

“…The animals treated with the respective drugs were euthanized by decapitation under deep anesthesia with carbon dioxide 24 hr after the last administration of the drug. Liver microsomes were prepared according to the method of Omura and Sato [ 25 ] and the procedure of the preparation followed those described in a previous report [ 31 ]. The protein concentration of the microsome fraction was determined by the method of Lowry et al .…”

“…In the current study, chickens treated with 125 mg/g of FZ had a decrease in sleep time associated with a significant increase in HXOH activity, whereas those given 62.5 mg/kg of FZ showed a similar decrease in sleep time, but no significant increase in HXOH activity. The decrease in sleep time may therefore be attributable to an increase in HXOH activity, in combination with a significant increase in relative liver weight and /or NADPH P450 reductase activity [ 31 ]. Figure 2

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