carbadox and cyadox

The aim of this article is to get an overview of the metabolism of quinoxaline 1,4-di-N-oxides (QdNOs) used in food animals. The derivatives of QdNOs (carbadox, olaquindox, mequindox, quinocetone, and cyadox) are the potent synthetic antimicrobial agents that are used for improving the feed efficiency and controlling dysentery in food-producing animals. Studies have demonstrated that the toxicity of QdNOs is closely associated with the production of their metabolism, especially with the production of their reduced metabolites. To the best of our knowledge, no one has systematically compiled the metabolism data of QdNOs. Therefore, the metabolism of QdNOs in animals has been discussed in the review for the first time. These drugs undergo extensive metabolism prior to excretion. N-oxide group reduction is the major metabolic pathway of QdNOs. Moreover, the N1- and N4-oxide reductions of QdNOs by different reducing mechanisms are also described. Obvious differences in metabolic pathways for QdNOs were observed owing to the differences on the side chain of these drugs. Therefore, understanding the metabolic pathways of QdNOs in animals will provide the guides for further studies of metabolism and toxicology of these drugs, and will also provide abundant information for the food safety assessment.

Topics: Animals; Carbadox; Humans; Quinoxalines

Olaquindox, carbadox, and cyadox are chemically synthesised antibacterial and growth-promoting agents for animals. At high doses they may exert mutagenicity and hepatic and adrenal toxicities in animals. Regrettably, these substances are frequently abused or misused when added into animal feeds. Thus, developing a sensitive and reliable method for simultaneous determination of olaquindox, carbadox, and cyadox in different kinds of animal feeds is crucially important for food safety monitoring. In this paper we optimised instrumental conditions, extraction solvents, solid phase extraction cartridges, and pH of the loading solvents on the Oasis HLB cartridge. Under the optimal conditions, mean recoveries ranged from 74.1 to 111%, and intra-day and inter-day variations were lower than 14.6% and 10.8%, respectively. The limits of quantification for olaquindox, carbadox, and cyadox were 0.05 mg kg

Topics: Animal Feed; Animals; Anti-Bacterial Agents; Carbadox; Chromatography, High Pressure Liquid; Hydrogen-Ion Concentration; Quinoxalines; Solid Phase Extraction; Tandem Mass Spectrometry

An experiment was designed to study the clinical effects of different levels of carbadox, cyadox and olaquindox in the ration on health, weekly weight gain and feed conversion in pigs. Four different carbadox and olaquindox (25, 50, 100 and 200 ppm) levels and five different cyadox (25, 50, 100, 200 and 400 ppm) levels were tested in groups of 6 pigs during 6 weeks. The 13 groups were compared with a control group fed on the same diet with only vehicle. After one week the first clinical sign, a high faecal dry matter (FDM) content, was observed in the 200 ppm carbadox group, followed by the 100 and 50 ppm carbadox, the 400 and 100 ppm cyadox, and the 200 and 100 ppm olaquindox groups two weeks later. A second clinical sign, urine drinking from the floor or from pen-mates, was observed in the same pens, occurring in the same sequence. The third important clinical sign, a decreased abdominal volume, was also observed in almost the same sequence, however, in the 50 ppm olaquindox and cyadox groups this clinical sign was not observed. Average weekly weight gain was significantly decreased in the higher carbadox and olaquindox groups. Weight gain was significantly increased in the 200 ppm cyadox group. Hematocrit values were significantly increased in the 200 and 100 ppm carbadox groups only. From this study one may conclude that, within the dosages used, carbadox is more harmful than olaquindox for pigs, and it seems that cyadox is harmless for pigs in dosages up to 400 ppm.

Topics: Animals; Anti-Bacterial Agents; Carbadox; Female; Hematocrit; Male; Quinoxalines; Swine; Weight Gain

Quindoxin (quinoxaline-1,4-dioxide), a former 'growth promoter' used in animal husbandry, has been taken from the market because of its photoallergic properties. Nowadays its derivatives olaquindox, carbadox and cyadox are frequently applied for the same purpose. Recent reports show that olaquindox too, can induce photoallergic skin reactions in stockmen. From the present investigation it appeared that all compounds mentioned, form a reactive oxaziridine upon exposure to light, just like many other imino-N-oxides. Photoreactivity with protein, which is considered as an important condition for a compound to be a potential photoallergen, was also studied. Quindoxin and olaquindox proved to meet this condition, as was expected. But carbadox and cyadox also react and were shown to be even more reactive towards human serum albumin.

Topics: Animals; Anti-Bacterial Agents; Carbadox; Chemical Phenomena; Chemistry; Humans; Organophosphorus Compounds; Photochemistry; Photosensitivity Disorders; Proteins; Quinoxalines; Serum Albumin; Ultraviolet Rays

To study the effects of olaquindox and cyadox on aldosterone, sodium and potassium in the blood in comparison with the effects of carbadox, weaned pigs were fed these compounds in different doses. Pigs treated with 100 and 200 ppm carbadox showed a significant decline of aldosterone after five and three weeks, respectively, compared with control values. In the 200 ppm group treatment was interrupted at week 4. With olaquindox a continuous, significant decline was found from 50 ppm and above after five weeks, and from 25 ppm and above (but excluding the 100 ppm group), after six weeks. In the cyadox groups a significant decline was measured after six weeks in the 50, 200 and 400 ppm groups. Only the 200 ppm group had an earlier response at three and five weeks. A decrease of sodium to hyponatraemic levels in the carbadox groups was seen after three weeks in the 200, and after five weeks in the 100 ppm group. In the olaquindox groups only the 200 ppm dosage showed a consistent decrease to hyponatraemic levels from four weeks treatment. In the cyadox groups the 200 ppm dosage reached a hyponatraemic level after six weeks. An increase of potassium to hyperkalaemic levels occurred at 100 and 200 ppm carbadox dosage after four and three weeks, respectively, and at 200 ppm olaquindox dosage after four weeks. No hyperkalaemic levels were seen in the cyadox groups. It is concluded that the toxic effect of olaquindox, despite minor differences, is comparable with that of carbadox but that cyadox is less toxic.

Topics: Aldosterone; Animal Feed; Animals; Anti-Bacterial Agents; Carbadox; Female; Male; Potassium; Quinoxalines; Sodium; Swine

Topics: Animals; Bone Marrow; Bone Marrow Cells; Carbadox; Chromosome Aberrations; Growth Substances; Male; Mice; Mice, Inbred ICR; Quinoxalines

The growth-promoting agents carbadox and olaquindox were active in the mouse transplacental micronucleus test, whereas cyadox was ineffective. Chemicals were administered p.o. and i.p. at a dose of 100 mg/kg and the effect was observed 18 h after treatment. The effects observed in fetal liver were parallel to those in maternal bone marrow, but fetal tissue was approximately 2-3 times more sensitive.

Topics: Administration, Oral; Animals; Bone Marrow; Carbadox; Cell Nucleus; Female; Fetus; Injections, Intraperitoneal; Liver; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Pregnancy; Quinoxalines

The cytogenetic activities of 3 growth-promoting agents carbadox, olaquindox and cyadox were examined by the micronucleus test. These chemicals were administered i.p. to male Wistar rats 30 and 6 h before they were killed. Single-dose levels were 5, 10, 15, 30, 60, 90, 120 and 240 mg/kg for carbadox; 30, 60, 90, 120 and 240 mg/kg for olaquindox; and for cyadox 30, 60, 120 and 240 mg/kg. Over the entire dose range tested, carbadox induced a statistically significant increase in the number of micronucleated polychromatic erythrocytes in the rat bone marrow, whereas similar activity of olaquindox started at a dose of 2 X 60 mg/kg. The effect of cyadox was very low even at the highest dosage tested. Further testing of the genotoxicity of this class of chemicals is required. The genetic activity of the solvent used (dimethyl sulfoxide) is briefly discussed.

Topics: Animals; Anti-Bacterial Agents; Bone Marrow; Carbadox; Cell Nucleus; Erythrocytes; Male; Mutagenicity Tests; Mutagens; Mutation; Quinoxalines; Rats; Rats, Inbred Strains; Structure-Activity Relationship

The effect of growth stimulators Carbadox and Cyadox was studied in laboratory rats and mice as exerted on their fertility, gravidity, embryo ontogenesis, and genetic efficacy of these drugs was also tested. In all tests one dose approaching the dose used in practice and multiple doses were administered. No antifertility effects were observed in either sex of rats, slight reduction in fertility was found in treated male mice. No teratogenic effect was observed, but both stimulators acted highly embryotoxically. Irrespective of the dose, genetic hazard occurred, influencing the first stages of spermatogenesis (spermatogony), and increasing the incidence ob abnormalities of spermatozoon heads after Carbadox treatment. In all tests Cyadox was less harmful than Carbadox. The results show that it is somewhat hazardous to use both growth stimulators in the period of animal reproduction.

Topics: Animals; Carbadox; Female; Fertility; Fetal Death; Fetus; Growth Substances; Male; Pregnancy; Pregnancy, Animal; Quinoxalines; Rats; Spermatogenesis