Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice

Shuhua, Xiao; Chollet, Jacques; Utzinger, Jürg; Mei, Jin-Yan; Jiao, Pei-Yin; Keiser, Jennifer; Tanner, Marcel

doi:10.1007/s00436-009-1471-4

Cited by 29 publications

(26 citation statements)

References 33 publications

(29 reference statements)

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“…Promising activities of the antimalarial mefloquine against biologically related trematodes, the schistosomes, had been described recently. When the adult schistosomes were exposed to mefloquine at concentrations of 20 and 30 lg/ mL, the process of the drug against the worms was fast that over 50 % of the worms died within 4 h, and the remaining worms died within 24 h, demonstrating that mefloquine exhibited a direct killing effect on adult schistosomes in vitro (Xiao et al 2009a). Besides, exposure of adult S. japonicum to mefloquine in vivo resulted in extensive damage of the worm's digestive system, tegument, musculature, parenchymal tissues, and reproductive system (Xiao et al 2009b).…”

Section: Discussionmentioning

confidence: 99%

“…In 2008, mefloquine, an amino alcohol antimalarial drug used widely in the treatment and prophylaxis of malaria for about 40 years, was reported to be effective in significant reduction of egg production in Schistosoma mansoni-infected mice after administration of a single dose of 150 mg/kg, but the drug had no effect on worm burden (Van Nassauw et al 2008). Recently, mefloquine was shown to exhibit anti-schistosomal properties against both, juvenile and adult parasites of S. mansoni and S. japonicum in vitro (Xiao et al 2009a;Manneck et al 2010Manneck et al , 2011Holtfreter et al 2011). As the tegument is one of the main absorptive surfaces for the uptake of drugs by the fluke (McKinstry et al 2003), the present study was undertaken to evaluate changes in tegument of adult F. gigantica following exposure to mefloquine in vitro.…”

Section: Introductionmentioning

confidence: 99%

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In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine

Shalaby¹,

Namaky²,

Kamel

2014

J Parasit Dis

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Emergence of drug-resistant Fasciola strains has drawn the attention of many authors to alternative drugs. The purpose of this study is to explore the in vitro effect of the antimalarial mefloquine against adult Fasciola gigantica. Light and scanning electron microscopic observations could be used to determine the target of the drug following 6 and 12 h of incubation in medium containing mefloquine at three different concentrations 10, 20 and 30 lg/mL, as morphological changes could be observed. These changes occurred in definite sequences in response to mefloquine, and were consisted of swelling, vacuolization that was later disrupted, leading to desquamation of the tegument, resulting in exposure and disruption of basal lamina and the dislodging of spines. It is concluded that mefloquine presented itself as a drug that might become important in trematode chemotherapy, with the tegument being an important drug target.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine

Shalaby¹,

Namaky²,

Kamel

2014

J Parasit Dis

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“…Histopathological observations identified that when mice infected with 14-day-old juvenile and 35-day-old adult S. japonicum were treated orally with mefloquine at a single dose of 400 mg/kg, an extensive and severe damage to the juvenile and adult schistosome was observed which resulted in death of worm and formation of dead worm abscess and granuloma Xiao and Zhang 2009). Further observation on morphological alteration of adult schistosomes harbored in mice treated with mefloquine demonstrated that the drug exhibited a rapid onset of action on schistosomes and induced extensive morphology damage to tegument, digestive system, and reproductive system (Xiao et al 2009a). All the results provide the strong evidence of in vivo activity of mefloquine against both juvenile and adult schistosomes.…”

Section: Introductionmentioning

confidence: 97%

Further study on mefloquine concerning several aspects in experimental treatment of mice and hamsters infected with Schistosoma japonicum

Shuhua

Mei²,

Jiao³

2009

Parasitol Res

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Antischistosomal properties of mefloquine against Schistosoma japonicum have been further studied. A total of 260 mice were divided into four batches, and three batches of them were infected percutaneously with 40 S. japonicum cercariae. In the remaining batch, mice were infected with 20, 40, or 80 S. japonicum cercariae. Other 45 hamster, divided into two batches, were each infected two or three times with 50 S. japonicum cercariae at days 0 and 7 or 0, 14, and 21. The infected mice and hamsters were treated orally with single doses of mefloquine or praziquantel at various intervals post-infection, while infected but untreated mice and hamsters served as control. All treated animals were killed 4 weeks post-treatment for assessment of effect. In hamsters concurrently infected with 14- and 21-day-old or 14-, 21-, and 35-day-old schistosomes and treated orally with mefloquine at a single dose of 100 and 200 mg/kg, the total worm burdens were significantly lower than that of control (P < 0.05 or P < 0.01) with worm burden reductions of 45.4% and 89.9% as well as 82.5% and 90.6%, respectively. In the first batch of mice treated with mefloquine and four structurally related amino alcohol antimalarials 5 weeks post-infection at a single dose of 400 mg/kg, mefloquine, quinine, and quinidine possessed similar potential effect with total worm burden reductions of 80.9-90.3%, while halofantrine and lumefantrine showed moderate and poor effect with total worm burden reductions of 67.5% and 38.4%, respectively. In the second batch of mice infected with 20, 40, and 80 S. japonicum cercariae and treated orally with mefloquine at a single dose of 200 and 400 mg/kg 5 weeks post-infection, similar effects were seen in groups of mice with various infection intensity, the total worm burden reductions were 59.9-73.0% (200 mg/kg) and 85.0-89.1% (400 mg/kg). In the other two batches of mice infected with various stages of schistosomes and treated orally with mefloquine and praziquantel at a single dose of 200 or 400 mg/kg, potential and moderate effects of praziquantel against d0 worms (3-h-old) and adult worms (28- and 35-day-old) with total worm burden reductions of 83.6-95.6% and 42.4-69.3% were observed, but no effect against various stages of juvenile schistosome was seen. Under the two single doses used, mefloquine exhibited no effect against d0 worms, but showed moderate or potential effect against various stages of juvenile and adult schistosomes with total worm burden reductions of 56.3-89.1% (200 mg/kg) and 81.1-100% (400 mg/kg). The results indicate that mefloquine shows potential effect on hamsters concurrently infected with various stages of juvenile and adult S. japonicum; among the four structurally related amino alcohol antimalarials tested, quinine and its isomer quinidine exhibit potential effect against adult S. japonicum similar to that of mefloquine, while halofantrine and lumefantrine posses moderate and poor effect; no impact of infection intensity on the effect of mefloquine against schistosomes was observed i...

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“…Morphological observation indicated that mefloquine exhibited a rapid onset of action and caused extensive morphologic damage to adult S. japonicum which included severe dilatation of gut, focal swelling of worm body, damage to reproductive glands (ovary, vitelline gland, and testis), and interference with ova formation (Xiao et al 2009b). Histopathological study provided further evidence of in vivo activity of mefloquine against adult schistosomes, which is revealed in focal roughing and vesiculation of the tegument, swelling of muscles and parenchymal tissues, dilatation of the gut accompanied by decrease in pigment particles, focal desquamation of gut epithelial cells, and degeneration of oocytes as well as vitelline gland cells.…”

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confidence: 99%

Transmission electron microscopic observation on ultrastructural alterations in Schistosoma japonicum caused by mefloquine

2010

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The purpose of the study was to explore the ultrastructural alterations of adult Schistosoma japonicum induced by mefloquine. Eight out of ten mice infected with 60-80 S. japonuicum cercariae for 35 days were treated orally with mefloquine at a single dose of 400 mg/kg. Four groups of two mice were killed at 8 h, 24 h, 3 days, and 7 days post-treatment, and schistosomes were collected by perfusion technique, fixed, and examined under a transmission electron microscope. Schistosomes obtained from the remaining two mice served as control. Eight hours after mefloquine 400 mg/kg was administered to the infected mice, various alterations in the tegument and subtegument tissues of both male and female worms were seen, which included focal lysis of tegmental matrix resulted in vacuole formation, decrease in rod-like and discoid-like secretary bodies, light swelling or focal lysis of musculature, extensive lysis of internal structure of sensory organelles, and appearance of vacuole or myelin-like structure in perinuclear cytoplasm of syncytium and epithelial cells. In vitelline cells of female worms, the most significant alteration was extensive lysis or fusion of vitelline balls in vitelline droplets and decrease in granular endoplasmic reticulum Twenty-four hours post-treatment, damage to the tegument and subtegument tissues had increased in severity. In male worms, the most prominent alterations were emergence of large vacuoles in the tegument, detachment of cytoplasmic process from the tegumental surface, focal collapse of internal structure of sensory organelle, and loss of definition of syncytium and gut epithelial cell. In female worms, focal lysis in tegumental matrix, musculature, and parenchymal tissues resulted in emergence of vacuole or myelin-like structure, reduction of nucleoli, fusion of partial nuclear membrane together with cytoplasm in epithelial cell, and lysis of interstitial tissues among the vitelline cells which were universal. Three and 7 days post-treatment, besides the aforementioned alterations, the significant damage to the male worms were disrupted outer plasma membrane detached from the cytoplasmic process, swelling of individual cytoplasmic process, extensive swelling and focal lysis in the musculature, parenchymal tissues and perinuclear cytoplasm of syncytium, accompanied by emergence of swollen mitochondria, vacuoles, and myelin-like structure, and severe damage to gut epithelial cell. In female worms, apart from disruption of outer plasmic membrane in cytoplasmic process, severe swelling of tegumental matrix accompanied by emergence of vacuoles, swollen mitochondria and myelin-like structure, focal lysis of heterochromatin and nucleoli, disappearance of microvilli in gut epithelial cells, and emergence of myelin-like structures in vitelline cells were observed. The results indicate that administration of mefloquine to mice infected with adult S. japonicum exhibits an extensive damage to the ultrastructure in tegument and subtegument tissues including syncytium, gut epithelial cells, pa...

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Effect of single-dose oral mefloquine on the morphology of adult Schistosoma japonicum in mice

Cited by 29 publications

References 33 publications

In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine

In vitro tegumental alterations on adult Fasciola gigantica caused by mefloquine

Further study on mefloquine concerning several aspects in experimental treatment of mice and hamsters infected with Schistosoma japonicum

Transmission electron microscopic observation on ultrastructural alterations in Schistosoma japonicum caused by mefloquine

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