Experimental benznidazole encephalopathy: II. Electroencephalographic and morphological alterations

Flores-Vieira, Carmen; Chimelli, Leila; Fernandes, Regina Maria França; Barreira, Amilton Antunes

doi:10.1016/s0022-510x(97)05362-8

Cited by 13 publications

(13 citation statements)

References 7 publications

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“…Under experimental conditions, apathy, ataxia, spastic tetraplegia with hyperreflexia of stretching reflexes, balance disorders, asymmetrical gait, and electroencephalographic alterations were described in mongrel dogs treated with doses of benznidazole ranging from 5 to 40 mg/kg/day. 16,17 Histopathologically, those alterations correlated with various types of lesions affecting the meninges, cerebral cortex, hemisphere white matter and subcortical gray matter, brain stem, cerebellum, and the spinal cord. 17 Determining long-term toxicity of nitroderivative chemotherapy requires monitoring for several years.…”

Section: Discussionmentioning

confidence: 98%

“…16,17 Histopathologically, those alterations correlated with various types of lesions affecting the meninges, cerebral cortex, hemisphere white matter and subcortical gray matter, brain stem, cerebellum, and the spinal cord. 17 Determining long-term toxicity of nitroderivative chemotherapy requires monitoring for several years. Its chronic toxicity in terms of tumor growths should be measured epidemiologically, because nifurtimox and of benznidazole administered to rabbits resulted in lymphoma growth in 36.5% of treated animals; untreated controls showed no growth.…”

Section: Discussionmentioning

confidence: 98%

“…[9][10][11] However, these drugs cannot be administered without the supervision of a physician because they provoke undesirable side effects. 12,[15][16][17] In addition, their efficacy for treating chronic Chagas disease has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

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Progressive chronic Chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitroderivatives.

Lauria-Pires

Braga²,

A³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

115

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Abstract. A randomized ten-year follow-up study involving 91 Chagas patients and 41 uninfected controls was undertaken to determine the effectiveness of nitroderivative therapy. Anti-Trypanosoma cruzi antibodies were consistently lower one year after treatment than 10 years thereafter (P Ͻ 0.001). The blood of all treated and 93.7% of untreated Chagas patients yielded polymerase chain reaction (PCR) product from probes annealing to T. cruzi nuclear DNA, indicating active infection. Competitive PCR showed means Ϯ standard deviations of 20.1 Ϯ 22.6 T. cruzi/ml of blood from untreated and 13.8 Ϯ 14.9 from treated Chagas patients, but the differences between means were not statistically significant (P Ͼ 0.05). Electrocardiograms recorded a gamut of alterations several-fold more frequent in Chagas patients, regardless of treatment, than in uninfected controls (P Ͻ 0.001). These results show that nitroderivative therapy for T. cruzi infections is unsatisfactory and cannot be recommended since it fails to eradicate the parasite or change the progression of heart disease in chronic Chagas patients.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

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Progressive chronic Chagas heart disease ten years after treatment with anti-Trypanosoma cruzi nitroderivatives.

Lauria-Pires

Braga²,

A³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

115

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“…These latter alterations are suggestive of encephalopathy with multifocal characteristics. Histopathologically, these alterations correlated with various types of lesions affecting the meninges, cerebral cortex, hemisphere white matter and subcortical gray matter, brain stem, cerebellum and the spinal cord 23 .…”

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confidence: 88%

“…Benznidazole produced fewer side effects and 70% of the patients took the drug dose for 60 days. Under experimental conditions, apathy, ataxia, spastic tetraplegia with hyperreflexia of stretching reflexes, balance disorders, asymmetrical gait, and electroencephalographic alterations were recorded in mongrel dogs treated with doses of benznidazole ranging from 5 to 40 mg/kg/day 22,23 . These latter alterations are suggestive of encephalopathy with multifocal characteristics.…”

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confidence: 99%

The treatment of Chagas disease patients with nitroderivative is unsatisfactory

2001

Rev. Inst. Med. trop. S. Paulo

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Re: "Persistent infections in chronic Chagas' disease patients treated with anti-Trypanosoma cruzi nitroderivatives" "Then I would still have this consolation -my joy in unrelenting pain -that I had not denied the words" … Brasília, March 3, 2001Sir,We are honoured to respond to the "Letter to the Editor", which was signed and forwarded for publication in the current issue of this journal by J. Romeu Cançado. First of all, we would like to praise him for the keen interest to open this important subject for discussion, thus recognizing that the treatment of Chagas disease patients with nitroderivatives is as yet unresolved for many physicians assisting people with this life threatening infectious disease, and for us. With respect to this, we appreciate Cançado's acknowledgment of the merit of our article recently published in this journal 6 , whereas we fully reject his comment that "the results shown do not support the conclusion drawn". On the other hand, we clearly understand Cançado's awareness that there is "controversy concerning the etiological treatment of chronic Chagas Disease, chiefly because there is no consensus for the criterion of cure". This controversy may be explained by lack of randomisation of research protocols, and by different criteria in obtaining data published by several authors in the last three decades. We believe that nitroderivatives may be life saving in those few patients with severe clinical manifestation of acute T. cruzi infection, or in immunosuppressed patients undergoing reactivation of the infection, only. We do not indicate treatment of the chronic T. cruzi infections, because we have not found a single benefit resulting from treatment of these Chagas patients with anti-trypanosoma drugs. In conjunction, it holds true that chemotherapy of T. cruzi infections with either benznidazole or nifurtimox nitroderivative is unsatisfactory and cannot be recommended since it fails to eradicate the parasite or to change the progression of heart disease in Chagas patients. Nitroderivatives used for treatment of Chagas Disease:The nifurtimox [4-(5-nitro-phurylideneamino-) tetrahydro-4-4-1, 4-thiazine-1-1-dioxide], and benznidazole [N-benzyl-2-nitro-imidazoleacetamide) are anti-trypanosoma nitroderivatives used to treat T. cruzi infections. Severe cytotoxicity has been described for several nitroderivatives, and, in recent decades, these compounds have been shown to possess a variable degree of mutagenic, teratogenic, carcinogenic and sterilizing activities 4,5,16,17,27,30,37,44,45,47 . Cytotoxicity and genotoxicity associated with nitroderivatives seem to depend on the binding of electrophilic radicals to macromolecules and DNA, after enzymatic reduction of the nitro-group and generation of free electrophilic radicals, such as nitro-anions, hydroxyl, singlet oxygen and hydrogen peroxide 18,21,30,31,41 . The drug toxicity targets the parasite and the mammalian host cell 18,27 . Table 1 shows data from nine research groups of treated acute or recent T. cruzi infections in different regions...

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