Disease relevance of Toltrazuril

• Comparative studies on the efficacy of sulphachlorpyrazine and toltrazuril for the treatment of caecal coccidiosis in chickens [1].
• In the battery studies, both drugs prevented coccidiosis-related mortality and decrease of weight gain to a similar degree, but toltrazuril was more effective in reducing intestinal lesions and faecal scores, when treatments were initiated 24 h postinfection [1].
• One group was treated with 15 mg toltrazuril/kg body weight, and a second group served as the sham-treated control [2].
• Attempted chemoprophylaxis of cryptosporidiosis in chickens, using diclazuril, toltrazuril, or garlic extract [3].

High impact information on Toltrazuril

• Evidence based on thermal stability and enzyme inhibition data suggests that the sulfoxidation of the drug toltrazuril by rat liver microsomes is catalyzed by different cytochromes P-450 [4].
• The relative rate of formation of the two toltrazuril enantiomers [(A)- and (B)-sulfoxides] depends on the source of the microsomes, suggesting that different cytochromes P-450 have different stereoselectivities [4].
• The efficacies of 20 mg/kg body weight (BW) of toltrazuril (Toltra) 2 days post-infection (dpi), 2 mg/kg BW of diclazuril 2 and 3 dpi and 200 mg/kg BW of sulphadimidine 2, 3 and 4 dpi were compared in a model for piglet isosporosis [5].
• Histopathology revealed mostly villous necrosis and atrophy in the small intestines except the duodenum, which peaked at 7 dpi, in all groups except Toltra [5].
• In summary, we concluded that (1) serology was not an entirely appropriate tool to answer our initial question and (2) toltrazuril has the potential to eliminate N. caninum in newborn calves [6].

Chemical compound and disease context of Toltrazuril

• However, clinical coccidiosis occurred in a large proportion of medicated control birds and these chickens had to be treated with anticoccidial drugs (Diclazuril and Toltrazuril) [7].
• Reduced weight gain and diarrhoea caused by Isospora suis was controlled by a single application of Toltra in the pre-patent period, while neither diclazuril nor sulphadimidine improved the clinical picture of isosporosis [5].

Biological context of Toltrazuril

• Our results suggest that toltrazuril primarily affects the respiratory chain and secondarily, two enzymes involved in pyrimidine synthesis [8].
• Thus, Toltrazuril does not impair the parasite specific intestinal cellular and systemic antibody response and does not prevent the development of protection against challenge infection [9].
• The pharmacokinetics of the antiparasitic drug toltrazuril (1-methyl-3-[3-methyl-4-[4-[trifluoromethyl]thio]phenoxy]phenyl- 1,3,5-triazine-2,4,6(1H,3H,5H)-trione) were studied in the rat following pretreatment with 3-methylcholanthrene, an inducer of rat liver cytochrome P-450 1A [10].
• Disinfection, floor type or treatment with toltrazuril did not affect the frequency of observation of oocysts [11].

Anatomical context of Toltrazuril

• Following treatment with toltrazuril, birds inoculated with high doses of oocysts were immune to subsequent challenge [12].
• This is supported by the fact that: (1) although the lack of B-cells did not impair the effect of toltrazuril, (2) the lack of T-cells did not allow for a full efficacy of treatment [13].
• Toltrazuril does not interfere with the process of parasite protein recognition by the immune system during infection [14].
• A symmetric triazinone, toltrazuril, was tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus) [15].
• Therefore, it is likely that the sensitivity of apicomplexans to the herbicide toltrazuril depends on the interaction of the herbicide with the D1 protein of the photosynthetic reaction center of the parasite's organelles [16].

Associations of Toltrazuril with other chemical compounds

• Effects of toltrazuril and ponazuril on Hammondia heydorni (syn. Neospora caninum) infections in mice [17].
• The anticoccidial properties of toltrazuril in Eimeria falciformis-infected mice were potentiated by the simultaneous application of pyrimethamine, trimethoprim, or sulfadimidine [8].
• Discontinuous medication with toltrazuril, given in the drinking water at a concentration of 50 ppm, was effective in controlling infection resulting from repeated inoculation of oocysts of a line of E. tenella partly resistant to monensin [12].
• Activities of some enzymes of the respiratory chain, such as succinate-cytochrome C reductase and NADH oxidase and succinate oxidase from mouse liver, were reduced in the presence of toltrazuril [8].
• Common carp fingerlings fed diclazuril, lasalocid, robenidine HCl or maduramicin and killed on day 14 after exposure were free from infection, while other groups treated with amprolium, toltrazuril, monensin Na, narasin or salinomycin Na harboured oocysts in the mucus and epithelium of the gut [18].

Gene context of Toltrazuril

• Toltrazuril also showed an inhibitory effect on the dihydroorotate-cytochrome C reductase from mouse liver [8].
• The number of cells releasing IFN-gamma or IL-4 was not dependent on the status of infection or previous treatment with Toltrazuril [9].

Analytical, diagnostic and therapeutic context of Toltrazuril

• Thirdly, there is a tendency for a higher IgG response after treatment with toltrazuril [14].
• Therefore, chemotherapy with toltrazuril against experimental infections with N. caninum requires the support of T-cell immunity in order to be successful [13].
• Chemoprophylaxis of coccidiosis in lambs with a single oral dose of toltrazuril [19].
• The infected cell cultures were incubated for 4-12 h in media containing 0, 1, 10 or 100 microg/ml of either toltrazuril or ponazuril [20].
• Fourthly, a higher antibody titre in IFAT, immunoblot and ELISA correlates with a higher reduction in oocyst excretion, lesion scoring and increased weight gains in toltrazuril-treated animals [14].

References