Neuropathologic toxicity of artemisinin derivatives in a mouse model.

Nontprasert, Apichart; Pukrittayakamee, Sasithon; Dondorp, Arjen M.; Clemens, Ralf; Looareesuwan, Sornchai; White, Nicholas J.

doi:10.4269/ajtmh.2002.67.423

Cited by 81 publications

(44 citation statements)

References 30 publications

(43 reference statements)

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“…Another possible exp lanation is that the drug may affect balance, and as such,upright posture. Earlier studies have shown that some nuclei of the Brainstem, especially those involved in auditory processing and vestibular reflexes, were selectively damaged by high and prolonged Artemisinin administration [8], resulting in abnormal gait and loss of balance.…”

Section: Discussionmentioning

confidence: 99%

“…the trapezoid nucleus, the gigantocellu lar reticu lar nucleus and the inferior Cerebellar peduncle [6]. In the rat, the target brainstem nucleus consistently and most severely affected is the nucleus of the trapezo id body [7] [8]. Changes in the affected neurons were loss of Nissl substance, perikaryonal swelling, margination of the nucleus (nucleus accentricity), nucleolar changes, and increased perikaryonal eosinophilia with occasional clu mp ing of eosinophilic debris [6].…”

Section: Background Informationmentioning

confidence: 99%

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Locomotor and Exploratory Behaviour in Mice with Treated Oral Artemether Suspension

Davies¹,

Ekpenyong²,

Nwangwa³

et al. 2013

NEUROSCIENCE

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Prev ious studies with intramuscular Artemether reveal dose dependent neurotoxicity with specific concern on the nuclei of the brain stem. This study was aimed at assessing the effect of oral Artemether suspension on locomotor and exploratory behaviour in mice. The study was conducted using a total of 30 mice randomly d ivided into 3 groups. Group 1 served as the control and was administered with neither drug nor placebo. Groups 2 and 3 were ad min istered with 30mg/ kg/day (low dose) and 60mg/kg/day (high dose) respectively of oral Artemether suspension for 17 days. Behavioural tools used were Open Field Maze, ElevatedPlus maze and Light/Dark t ransition box. Parameters measured were centre square duration/ entries, frequency of rearing, frequency of line crosses, open arm duration / entries and head dips. In the Open Field test, centre square duration and entries were significantly higher in the low dose group but lower in the high dose group compared to the control. The frequency of line crosses in the Open Field test was also significantly lower in the high dose group compared to control. The frequency of rearing was significantly lo wer in high dose group compared to the control in all the 3 behavioural tools used. There was no significant difference between the control and the experimental mice in the frequency of head dips and open arm duration/entries. In conclusion, oral Artemether causes reduce exploratory and locomotor activ ity.

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Section: Discussionmentioning

confidence: 99%

Section: Background Informationmentioning

confidence: 99%

Locomotor and Exploratory Behaviour in Mice with Treated Oral Artemether Suspension

Davies¹,

Ekpenyong²,

Nwangwa³

et al. 2013

NEUROSCIENCE

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“…Neurological findings included gait disturbance, loss of spinal and pain response reflexes, and prominent loss of brain stem and eye reflexes. It has been reported that artemether TM produces dose-dependent neuropathological damage to the brain-stem in the mouse (Nontprasert et al, 2002). The neurons in the lower brain-stem trapezoid nucleus, the gigantocellular reticular nucleus, and the inferior cerebella peduncle were the most sensitive to the toxic effects of artemether TM (Nontprasert et al, 2002).…”

Section: Introductionmentioning

confidence: 96%

“…It has been reported that artemether TM produces dose-dependent neuropathological damage to the brain-stem in the mouse (Nontprasert et al, 2002). The neurons in the lower brain-stem trapezoid nucleus, the gigantocellular reticular nucleus, and the inferior cerebella peduncle were the most sensitive to the toxic effects of artemether TM (Nontprasert et al, 2002). Most importantly, it has been shown that in vitro artemisinin induces oxidative stress in cultured neurons, as indicated by an increase in reactive oxygen species and extensive lipid peroxidation (Schmuck et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Histological and biochemical effects of Arteether<sup>tm</sup> on the liver of wistar rats

Okunlola

Okunlola²,

Okani³

et al. 2013

Afr. J. Trad. Compl. Alt. Med.

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Arteether TM is among the recent drugs that are used to combat chloroquine-resistant malarial parasites. This study examined the effects of arteether TM on enzyme biomarkers of the liver, serum protein concentrations, and liver morphology. Twenty (20) adult albino Wistar rats weighing 200 -250 g were randomly divided into four groups (A, B, C and D) of five animals each, and used in this study. Group A rats were given intramuscular (i. m.) arteether TM (3 mg/kg b. w.) daily for 3 days. Group B rats received i. m. arteether TM (6 mg/kg b. w.) daily for 3 days. Group C rats were given i. m. arteether TM (3 mg/kg b. w.) daily for 3 days. The same dose was repeated at two-weekly intervals for 4 further weeks, while group D rats which received normal saline (0.9 % w/ v, 3 ml/kg b.w.), served as controls. At the end of the experiment, the body weights of the animals were determined and recorded. Serum levels of alanine transaminase (ALT), aspartate transaminase (ASP), alkaline phosphatase (ALP), total protein (TP) and albumin were assayed, and histological studies were performed. Results obtained show no significant difference (P<0.05) in liver enzymes (ALT, ASP, ALP). TP and albumin were significantly reduced in group C rats. Histological studies revealed no cyto-architectural changes. It is concluded that at therapeutic doses, arteether TM is well tolerated in Wistar rats. .

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“…It is used in combination therapy and is effective in cases of uncomplicated P. falciparum. Several studies on artesunate showed evidence of toxicity on the brain stem [17,18], superior colliculus [19], stomach [20], testis [21] and liver [22]. The present study evaluated the toxicological influence of different artesunate dosage administration in Albino rats, as administered to human.…”

Section: Introductionmentioning

confidence: 99%

Effect of Oral Administration of Artesunate on the Histology of the Kidney in Albino Rat.

Amaza¹,

Momoh²,

Zirahei³

et al. 2013

IOSR-JDMS

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Abstract:The effect of oral administration of Artesunate on the histology of the Kidney of Albino Rat was determined histologically. Thirty Albino rats weighing 80-175g were divided into five groups (A-E) of five rats each. Group A (control) was give equal volume of distilled water daily. Group B received 4mg/kg/day of Artesunate for 5 days and were sacrificed on the 6th day. Group C were given 4mg/kg of Artesunate for the 1 st day, then 3mg/kg/day of Artesunate for 8 days and sacrificed on the 10 th day. Group D received 4mg/kg/day of Artesunate for the 1 st day, then 3mg/kg/day of Artesunate for 12 days and sacrificed on the 14 th day. Group E served as recovery group which received equal treatment as group D above and were left for 10 days later on vital feed and water and were sacrificed on the 23 rd day. The route of administration was orally by the use of the orogastric tube. The kidneys were removed and transferred immediately into 10% formalin. There were no marked differences between the change in weight of the control and the experimental. Administration of Artesunate to rats produced moderate to severe glomerular degeneration, focal haemorrhage, oedema, congested blood vessels, cloudy swelling of the tubules, necrosis of the tubule both in cortex and medulla. These findings were observed to be dose dependent. Artesunate may have acted as toxin to the neurons, affecting their structural integrity. It is therefore recommended that further studies aimed at corroborating this findings be carried out

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Neuropathologic toxicity of artemisinin derivatives in a mouse model.

Cited by 81 publications

References 30 publications

Locomotor and Exploratory Behaviour in Mice with Treated Oral Artemether Suspension

Locomotor and Exploratory Behaviour in Mice with Treated Oral Artemether Suspension

Histological and biochemical effects of Arteether<sup>tm</sup> on the liver of wistar rats

Effect of Oral Administration of Artesunate on the Histology of the Kidney in Albino Rat.

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