Mode of Action of Hetrazan in Filariasis

Hawking, Frank; Sewell, P.; Thurston, June P.

doi:10.1016/s0140-6736(48)91165-9

Cited by 25 publications

(17 citation statements)

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“…It is important to note that the dose utilized by these researchers was half of those frequently used in clinical procedures, which is 6 mg/kg (Bolla et al 2002). In the present work, the choice of using 5 μg/ml as the minor concentration of DEC was based on classical pharmacological studies (Hawking et al 1948). It represents about four times higher than those observed on plasma concentration as indicated by recent reports (Bolla et al 2002).…”

Section: Discussionmentioning

confidence: 90%

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Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

2008

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Apoptosis, a programmed cell death, is characterized by chromatin condensation, numerous vacuoles, reduction in cell volume, and endonuclease cleavage DNA degradation detected in gel electrophoresis as nucleosomal ladder. Here we report that diethylcarbamazine induces DNA fragmentation in microfilariae of Wuchereria bancrofti revealed by ligation-mediated polymerase chain reaction and by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling at the light and electron transmission level.

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Section: Discussionmentioning

confidence: 90%

“…Previous optical analyses revealed that the exposure of microfilariae to high concentrations of DEC left them unharmed; these results led to the idea that DEC had no direct effect on filarial parasites (Hawking et al 1948;Hawking and Laurie 1949;Hawking 1979;Johnson et al 1988).…”

Section: Introductionmentioning

confidence: 99%

Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

2008

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“…Previous studies showed that DEC has no effect on filarial parasites in vitro (Hawking et al 1948;Hawking and Laurie, 1949;Johnson et al 1988). These and many other observations led to the suggestion that DEC only stimulates host defense activity (for a review, see Maizels and Denham 1992).…”

Section: Discussionmentioning

confidence: 96%

The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro

Peixoto

Rocha

Aguiar-Santos

et al. 2004

Parasitology Research

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An ultrastructural study of microfilariae of Wuchereria bancrofti was performed after treatment in vitro and in vivo with diethylcarbamazine citrate (DEC). The morphological alterations produced by treatment in vitro with 5 micro g/ml of DEC were the loss of microfilarial sheaths and lysis of the cytoplasm, with the destruction of all organelles and the formation of several vacuoles, the contents of which presented various degrees of electron-density, or showed an empty appearance. Some of these vacuoles seemed to be extruding from the cytoplasm as apoptotic bodies and others presented organelles inside. Similar alterations were observed after in vivo treatment. At 40 min after treatment of a microfilaremic individual with DEC, almost all microfilariae observed had lost their sheaths; and, in some of them, remains of the microfilarial sheath on the larval surface could be detected. Numerous vacuoles were observed, mainly in the hypodermis and somatic cells, showing organelles inside or an empty appearance. Condensed chromatin was also observed in some somatic cells. At 1 h after treatment of a microfilemic individual with DEC, microfilariae presented drastic morphological alterations, with large vacuoles within somatic cell cytoplasm and complete lysis of all cellular organelles. Therefore, both treatments with DEC in vitro and in vivo had a direct mechanism of action on the microfilariae of W. bancrofti, including organelle damage and apoptosis.

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“…The present experiments were carried out on cotton rats bred at this Institute and infected with Litomosoides by the methods described by Hawking and Sewell (1948). The hetrazan used was the dihydrogen citrate, kindly supplied by American Cyanamid Co., and all doses refer to this salt.…”

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confidence: 99%

The Mode of Action of Hetrazan on Filarial Worms

Hawking

Sewell

Thurston

1950

British Journal of Pharmacology and Chemotherapy

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This paper describes an investigation of the antifilarial action of hetrazan in experimental animals, with special reference to the mechanism underlying its action. A preliminary communication on the work was given by Hawking, Sewell, and Thurston (1948).Hetrazan is-I -diethylcarbamyl-4-methylpiperazineThe antifilarial action of hetrazan was discovered and described by Hewitt, Kushner, Stewart, White, Wallace, and SubbaRow (1947) working with cotton rats infected with Litomosaides carinii, and its action on human filariasis due to W. bancrofti was shown by Santiago-Stevenson,-Oliver-Gonzalez, and Hewitt (1947). The present experiments were carried out on cotton rats bred at this Institute and infected with Litomosoides by the methods described by Hawking and Sewell (1948). The hetrazan used was the dihydrogen citrate, kindly supplied by American Cyanamid Co., and all doses refer to this salt. Microfilaria counts were made by spreading 5 to 20 cu.mm. of blood on a slide to form a thick film, dehaemoglobinizing in water, fixing in alcohol, and staining with hot haemalum or with Giemsa's stain; the microfilariae were then counted under the microscope.Preliminary experiments in vivo Infected cotton rats were given hetrazan by intraperitoneal injection according to the schedules shown in Table I and daily counts were made of the microfilariae in the blood taken from the tail. The rats were treated about seventy days after infection; during the next month untreated rats usually show a gradual increase in the microfilaria count. According to Harned et al. (1948) the LD50 of hetrazan hydrochloride when given intraperitoneally to rats is 465 mg./kg. In our experiments single intraperitoneal doses of 500 mg. of the citrate per kg. or hourly doses 100 mg./kg. usually caused prostration for 1-1 hour after each injection; repetition of the 500 mg./kg. dose after one day sometimes caused death, but 250 mg./kg. twice daily was well tolerated. The effect on the number of microfilariae in the blood varied considerably in different animals so that precise quantitative results

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Mode of Action of Hetrazan in Filariasis

Cited by 25 publications

References 1 publication

Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

Molecular evidence for apoptosis in microfilariae of Wuchereria bancrofti induced by diethylcarbamazine

The effects of diethylcarbamazine on the ultrastructure of microfilariae of Wuchereria bancrofti in vivo and in vitro

The Mode of Action of Hetrazan on Filarial Worms

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