Effects of toltrazuril and ponazuril on the fine structure and multiplication of tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia heydorni) in cell cultures

Darius, Anne Kathrin; Mehlhorn, Heinz; Heydorn, A. O.

doi:10.1007/s00436-003-1063-7

Cited by 34 publications

(30 citation statements)

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“…Other effects included distortion of the PVM, and degradation of the granular matrix of the parasitophorous vacuole. The effects appeared similar for all three drugs, and massive vacuolization of the cytoplasm of N. caninum and T. gondii tachyzoites was reported earlier also upon treatment of N. caninum-and T. gondii-infected cells with ponazuril (Darius et al 2004 ;Mitchel et al 2005). Darius et al (2004) also indicated that ponazuril was targeting the N. caninum apicoplast.…”

Section: Discussionsupporting

confidence: 81%

In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

et al. 2007

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S U M M A R YNitazoxanide (NTZ) and its deacetylated metabolite tizoxanide (TIZ) exhibit considerable in vitro activity against Besnoitia besnoiti tachyzoites grown in Vero cells. Real-time-PCR was used to assess B. besnoiti tachyzoite adhesion, invasion, and intracellular proliferation in vitro. A number of NTZ-derivatives, including Rm4822 and Rm4803, were generated, in which the thiazole-ring-associated nitro-group was replaced by a bromo-moiety. We here show that replacement of the nitro-group on the thiazole ring with a bromo (as it occurs in Rm4822) does not impair the efficacy of the drug, but methylation of the salicylate ring at the ortho-position in a bromo-derivative (Rm4803) results in complete abrogation of the antiparasitic activity. Treatment of extracellular B. besnoiti tachyzoites with NTZ has an inhibitory effect on host cell invasion, while treatments with TIZ, Rm4822 do not. TEM demonstrates that the effects of Rm4822 treatment upon the parasites are similar to the damage induced by NTZ. This includes increased vacuolization of the parasite cytoplasm, and loss of the structural integrity of the parasitophorous vacuole and its membrane. Thus, Rm4822, due to the absence of a potentially mutagenic nitro-group, may represent an important potential addition to the anti-parasitic arsenal for food animal production, especially in cattle.

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Section: Discussionsupporting

confidence: 81%

In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

et al. 2007

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“…In previous studies, although TZR has been shown to be effective in vivo against Eimeria species and in vitro against Toxoplasma gondii (Chapman, 1987;Ricketts and Pfefferkorn, 1993), TZR-SO 2 also has a potent and broad spectrum anticoccidial activity (Lindsay et al, 2000;Gottstein et al, 2001;Franklin et al, 2003). In one of the recent studies, TZR at 10 μg/mL and TZR-SO 2 at 30 μg/mL also led to a significant reduction in the multiplication rate of N. caninum (Darius et al, 2004). Mitchell et al (2005) reported that TZR-SO 2 at 5 μg/mL inhibited development of N. caninum after approximately 48 h post exposure in African green monkey kidney cell culture.…”

Section: Resultsmentioning

confidence: 94%

Pharmacokinetics and Metabolism of Toltrazuil and Its Major Metabolites after Oral Administration in Broilers

et al. 2013

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Toltrazuril is a symmetrical tiazinetrione compound. It is active against all intracellular developmental stages including those of schizogony and gametogony. In this study the disposition kinetics of toltrazuril (TZR) and its major metabolites (TZR-SO and TZR-SO 2 ) in broiler chickens after single oral administrations of 10 or 20 mg/kg were investigated. Mean plasma concentrations of TZR peaked at 16.4 and 25.2 μg/mL at 5.0 and 4.7 h after dosing, respectively. TZR was converted to the short-lived intermediary metabolite toltrazuril sulfoxide (TZR-SO), and then further metabolized to the reactive toltrazuril sulfone (TZR-SO 2 ) being actually more slow eliminated with 80.3 and 82. 9 h than TZR (10. 6 and 10. 7 h) or TZR-SO (14. 8 and 15. 3 h) in low and high dosing groups, respectively. Prolonged elimination half-life of TZR-SO 2 could be interpreted as the persistent clinical efficacy of TZR in the treatment of protozoal parasites infection.Key words: broiler, pharmacokinetics, toltrazuril, toltrazuril sulfone, toltrazuril sulfoxide J. Poult. Sci., 50: 257-261, 2013 Introduction Coccidiosis is a particularly dangerous disease in the poultry industry where chickens are maintained on the floor (Greif, 2000). Anticoccidial drugs of many different chemical types have been the dominant means to prevent and control the coccidiosis (Polozowski, 1993;Greif et al., 2001). However, the massive and uncontrolled use of anticoccidial drugs has resulted in the emergence of drug-resistant parasites (Suo X et al., 2006)., 5-triazinane-2, 4, 6-trione, is a symmetrical triazinetrione compound. It has coccidiocidal action against all intracellular developmental stages including those of schizogony and gametogony (Mehlhorn et al., 1984;Haberkorn and Stoltefuss, 1987). It has been reported to be effective against all coccidial species in most animal species, such as chickens (Mehlhorn et al., 1984), ducks (Chauve et al., 1994), dogs (Daugschies et al., 2000), mice (Haberkorn et al., 1983), pigeons (Van Reeth and Vercruysse, 1993), piglets (Mundt et al., 2007) and rabbits (Peeters and Geeroms, 1986).TZR undergoes extensive metabolism to toltrazuril sulfoxide (TZR-SO) and then to TZR-SO 2 , which appears to have anticoccidial activity (Benoit et al., 1993;Lang et al., 1996;Bach et al., 2003;Mundt et al., 2007) (Fig. 1). Generally, triazines produced the same types of metabolites in most species, but the ratios of the metabolites showed the species differences (Furr and Kennedy, 2000;MacKay, 2006;Kim et al., 2010;Lim et al., 2010). Also, TZR is almost exclusively metabolized to TZR-SO 2 , also known as ponazuril (PZR), which has been recognized as the marker metabolite in a number of tissues. Although TZR is commonly used for the prevention and treatment of coccidosis in broilers, the pharmacokinetic and metabolic profiles of TZR in broilers have received minimal investigation. There must be assessed not only in terms of good clinical efficacy but also considering the pharmacokinetics and metabolism of TZR in broilers for the rat...

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“…However, interesting experimental studies that may result in an option for chemotherapeutic control at a later stage have been conducted. An effect of toltrazuril and its derivative ponazuril on tachyzoites of N. caninum has been shown in vitro (104) and in vivo in calves (200,255). In calves treated with ponazuril, the parasite was no longer detectable in the brain and other organs (255).…”

Section: Control Measuresmentioning

confidence: 99%

Epidemiology and Control of Neosporosis andNeospora caninum

2007

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SUMMARY Neospora caninum is a protozoan parasite of animals. Until 1988, it was misidentified as Toxoplasma gondii. Since its first recognition in dogs in 1984 and the description of the new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of cattle and dogs worldwide. Abortions and neonatal mortality are a major problem in livestock operations, and neosporosis is a major cause of abortion in cattle. Although antibodies to N. caninum have been reported, the parasite has not been detected in human tissues. Thus, the zoonotic potential is uncertain. This review is focused mainly on the epidemiology and control of neosporosis in cattle, but worldwide seroprevalences of N. caninum in animals and humans are tabulated. The role of wildlife in the life cycle of N. caninum and strategies for the control of neosporosis in cattle are discussed.

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Effects of toltrazuril and ponazuril on the fine structure and multiplication of tachyzoites of the NC-1 strain of Neospora caninum (a synonym of Hammondia heydorni) in cell cultures

Cited by 34 publications

References 13 publications

In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

In vitro efficacy of nitro- and bromo-thiazolyl-salicylamide compounds (thiazolides) against Besnoitia besnoiti infection in Vero cells

Pharmacokinetics and Metabolism of Toltrazuil and Its Major Metabolites after Oral Administration in Broilers

Epidemiology and Control of Neosporosis andNeospora caninum

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