Studies On The Toxicity And Metabolism Of Sulfadimethoxine-Sodium In Ictalurus Punctatus

Sulfadimethoxine-sodium is a broad-spectrum antimicrobial drug, which is often used as feed additives and fishery drugs to prevent disease. However, the drug metabolism in fish needs a long time, bacteria will become resistant for excessive use. It would have some adverse effects on fish when the drug residues have a certain accumulation, excessive drug residues was toxic to humans. In this paper, effects of administration does and time of sulfadimethoxine-sodium on the toxicity to Ictalurus punctatus were studied, and the metabolism and residue of sulfadimethoxine-sodium in Ictalurus punctatus were studied under different conditions. The main research contents and results were as follows:1. Effects of administration does and time of sulfadimethoxine-sodium on the toxicity to Ictalurus punctatus were studied. Ictalurus punctatus were administered sulfadimethoxine-sodium five days at different drug does, the contents of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase and urea in plasma of treated group and control group (no administration) showed no significant difference. The content of creatinine in plasma was higher in the treatment group administered at dose of 400 mg/kg.bw than that of the control group. The content of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, alkaline phosphatase, urea and creatinine in plasma were higher in the treatment group than that of the control group after continuous administered ten days. There were no significant changes observed in liver, and the nucleus of renal tubule were migrated outward after Ictalurus punctatus administered with sulfadimethoxine-sodium at dose of 100mg/kg.bw. The liver had some changes, the boundaries of the cell membrane gradually became blurred, the nucleus deviated from the cell center, the renal tubule had some changes, renal tubule epithelial cells appeared vacuolar degeneration after Ictalurus punctatus were administered with sulfadimethoxine-sodium at dose of 200mg/kg.bw. The liver had local necrosis, liver cells showed nuclear fusion or cell lysis, renal tubule epithelial cells showed necrosis, shedding, etc, after Ictalurus punctatus were administered with sulfadimethoxine-sodium at dose of 400mg/kg.bw. Thus, sulfadimethoxine-sodium had no significant effect on the liver, and sulfadimethoxine-sodium had a certain effect on the kidney in high doses after continuous administration five days. Sulfadimethoxine-sodium had significant effect on the liver and kidney after continuous administration ten days.2. The metabolism and residue of sulfadimethoxine-sodium in Ictalurus punctatus were studied under different conditions. The optimum condition of high performance liquid chromatography:the mobile phase was acetonitrile:double distilled water=2:3, detection wavelength was 271nm, flow rate was 0.6 mL/min, a peak time was 9 min. The recovery rates were high in this experiment, the coefficients of variation were small, the minimum detection limit was 0.01μg/g. The metabolites of blood, muscle, liver and kidney were analysised by liquid chromatography mass spectrometry (LC-MS), the main metabolite was acetyl sulfadimethoxine-sodium.The metabolism of sulfadimethoxine-sodium in Ictalurus punctatus was the two-compartment model under different conditions, the metabolism had no significant difference under different conditions, but the higher adiministration dose, the higher residues in the organization. The maximum concentration in blood, muscle, liver, kidney were 12.27,11.05,4.87,5.55 mg/kg respectively when Ictalurus punctatus were administered with sulfadimethoxine-sodium at dose of 100 mg/kg.bw in (19±1)℃, which were 21.42,17.81,9.36,9.04 mg/kg when Ictalurus punctatus were administered at dose of 200 mg/kg.bw. The drug contents of various tissues were lower than the national minimum standards (0.1mg/kg) after 120 h under two kinds of concentration.The metabolism of sulfadimethoxine-sodium in Ictalurus punctatus had a significant difference under different temperatures, the higher temperature, the faster metabolism. The maximum concentration in blood, muscle, liver, kidney were 21.42,17.81,9.36,9.04 mg/kg when Ictalurus punctatus were administered with sulfadimethoxine-sodium at dose of 200 mg/kg.bw in (19±1)℃, which were 20.94,18.78,11.20,9.72 mg/kg in (27±1)℃. The drug contents of various tissues were lower than the national minimum standards after 120 h in (19±1)℃and 96 h in (27±1)℃.When Ictalurus punctatus were administered with sulfadimethoxine-sodium at dose of 200mg/kg.bw consecutively five days, the drug contents of blood, muscle, liver and kidney respectively were less than the national minimum standards after stopped administering 10,6,8,4 days. Therefore, the withdrawal period should be more than 10 days in this condition.