The effects of enrofloxacin on hepatic microsomal mixed function oxidases in broiler chickens

Abstract

Broiler chickens are raised under extremely intensive conditions with the emphasis in utilizing every day of their short 35-40 day lifespan to realize the potential of maximum weight gain. If the birds fall behind the planned growth rate there may be reduced profits for the fanner. Therefore, in many modern systems. mean body weight is constantly monitored, and within hours ofdetecting a reduction in projected weight gain, veterinarians and nutritionists can be alerted to fiid the cause of the setback. If a bacterial disease is diagnosed, the whole flock is o h n given feed or water medicated with an antibacterial drug. Ifthe response to this drug is not optimal. or antibiotic sensitivity tests indicate otherwise, another antibacterial agent may be administered. The emcacy of these drugs is dependent upon the dosage administered, the susceptibility of the pathogenic organism to that drug, the pharmaccdynamics of the drug in the broiler (a fairly constant factor which would have been examined in detail by the manufacturer), its pharmacokinetics in the broiler, and acquiring and maintaining a minimum inhibitory concentration (MIC) in the blood. Pharmacokinetics largely involves phase 1 metabolism in the liver mediated by enzymes, collectively called mixed function oxidases (MFO). The activity of the MFO can be elevated or depressed after exposure to many xenobiotics, and the metabolism of certain drugs given concomitantly or thereafter might also be changed.In view of the above facts, it is surprising that the topic of the effects of xenobiotics on MFO in broilers has been so little investigated. Our literature search revealed only three publications on MFO in commercial broiler chickens (Takahashi & Jensen, 1984; Brenes et d., 1985; Brenes et PI., 1990), with no mention of chemotherapeutic agents. Although considerable data exist on the effects of xenobiotics on MFO activity in laboratory animals (Yang et d., 1992), species dflerences (Walker, 1980) preclude a valid extrapolation to broilers and there clearly exists a tremendous knowledge deficit on this topic. Quinolones have been shown to inhibit Ndemethylation In humans (Staib et d.. 1987) and in laboratory anfmals (Mizukl etal.. 1989). but no such studies have been published on this promising group of antimicrobials which are now used in broilers. This work presents data on the d e c t of the ff uomquinolone antibiotic emfloxacin on the activity of MFO in broilers. Onedaydd male commercial broiler chicks were housed in electrically heated battery brooders. Broiler feed was supplied ad libitum throughout. When the birds were 25 days old, they were weighed and birds were chosen in a weight range of 525-650 g. Five gruups of 6-10 birds w e n randomly constituted. Four groups were dosed per os with emfloxacin (Barn, Bayer, Germany), according to the manufacturers' recommendations, at a dose of 10 mgkg body weight each day for 3 consecutive days: these groups diflered only in the time between emfloxacin dosage and MFO determination. One control group received no tr...

Marek's disease vaccination, with turkey herpesvirus, and enrofloxacin modulate the activities of hepatic microsomal enzymes in broiler chickens

“…Our results with ENR administered in low concentration (50 mg/L) to vaccinated chickens have shown that this drug inhibits the activity of the two enzymes tested in comparison to vaccinated non-treated group. Similarly, Schlosberg et al (1995) reported that 10 mg ENR/kg body weight, a dose roughly related to the ENR concentration of 50 mg/L used in the present study, transiently inhibited the activity of aniline hydroxylase and aminopyrine N-demethylase in chickens. Likewise, ENR has been reported to inhibit induction of drug metabolising enzymes in dogs (Novotny and Shaw, 1991), and its metabolite, ciprofloxacin, inhibits drug metabolism in mice ( Vancustem and Babish, 1993).…”

“…In addition, ENR has a good therapeutic effect, low toxicity, and negligible side effects. However, little information exists in the scientific literature about the effect of ENR on microsomal monooxygenase activity in poultry (Schlosberg et al, 1995).…”

Antibiotic effects on cytochromes P450 content and mixed‐function oxygenase (MFO) activities in the American alligator, Alligator mississippiensis

“…Ostensibly, the same mechanism was involved in the reaction of the alligators to the initial enrofloxacin dose causing them to quit feeding. Schlosberg et al . (1995) treated broiler chickens with a regimen of enrofloxacin (10 mg/kg for three consecutive days) and found no differences in mean liver weight between control and enrofloxacin‐treated chickens.…”

“…Cephalosporins have been shown to affect cytochromes P450 metabolism in mammals (Jordan et al ., 1994). Quinolones inhibit MFO‐dependent metabolism in humans (Davies & Maesen, 1989; Fuhr et al ., 1992) and in domesticated (Schlosberg et al ., 1995) and laboratory animals (Vancutsem & Babish, 1996). Enrofloxacin, a synthetic quinolone, decreases MFO‐dependent aniline hydroxylase and aminopyrine N‐demethylase activities in chickens (Schlosberg et al ., 1995), 7‐ethoxyresorufin (phenoxazone) O‐dealkylase (EROD) activity in rats (Vancutsem & Babish, 1996), and is currently being considered for use in aquacultured species in Europe and the United States (Schnick, 1991).…”

“…Quinolones inhibit MFO‐dependent metabolism in humans (Davies & Maesen, 1989; Fuhr et al ., 1992) and in domesticated (Schlosberg et al ., 1995) and laboratory animals (Vancutsem & Babish, 1996). Enrofloxacin, a synthetic quinolone, decreases MFO‐dependent aniline hydroxylase and aminopyrine N‐demethylase activities in chickens (Schlosberg et al ., 1995), 7‐ethoxyresorufin (phenoxazone) O‐dealkylase (EROD) activity in rats (Vancutsem & Babish, 1996), and is currently being considered for use in aquacultured species in Europe and the United States (Schnick, 1991). Enrofloxacin is effective as a broad‐spectrum antibiotic and is well‐tolerated in aquatic animals (Reimlinger et al ., 1990; Bowser & Babish, 1991; Dalsgaard & Bjerregaard, 1991).…”