A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in Sprague–Dawley rats

Teo, Sze Yiun; Stirling, David I.; Thomas, Steve; Hoberman, Alan M.; Kiorpes, Anthony L.; Khetani, Vikram

doi:10.1016/s0300-483x(02)00338-4

Cited by 311 publications

(216 citation statements)

References 14 publications

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“…In general, maternal deaths, reduction in body weight gain, and food and water intake are simple and sensitive indices of toxicity after exposure to toxic substances (Raza et al 2002, Teo et al 2002. In this study, the maternal weight gain did not differ.…”

Section: Anomaly Frequencysupporting

confidence: 47%

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats

Volpato

Francia-Farje

Damasceno

et al. 2015

An. Acad. Bras. Ciênc.

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Citrus aurantium L., commonly known as bitter orange, is widely used in folk medicine, but there is little data in the literature about the effects on pregnancy. The aim of the present study was to evaluate the influence of essential oil obtained from fruits of Citrus aurantium on the maternal reproductive outcome and fetal anomaly incidence in rats. Pregnant Wistar rats were randomized into four groups (n minimum = 12 animals/group): G1 = control, G2 to G4 = treated with essential oil from C. aurantium at dose 125, 250 and 500 mg/kg, respectively. Rats were orally treated, by gavage, with plant essential oil or vehicle during pre-implantation and organogenic period (gestational day 0-14). On gestational day 20 the rats were anaesthetized and the gravid uterus was weighed with its contents and the fetuses were analyzed. Results showed that the treated group with 500 mg/kg presented decreased placental weights and placental index, although the treatment with bitter orange essential oil did not show any alteration in maternal reproductive performance, toxicological effect, changes in ossification sites, and malformation index. In conclusion, the treatment of Citrus aurantium essential oil was not teratogenic and did not alter the maternal reproductive outcome.

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Section: Anomaly Frequencysupporting

confidence: 47%

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats

Volpato

Francia-Farje

Damasceno

et al. 2015

An. Acad. Bras. Ciênc.

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“…If MPD produced anorexia, one would hypothesize that performance would be inferior in an appetitive task. However, MPD did not alter body weight of the ad-lib fed males and females (see also Bolanos) [4] and has been shown to not affect food consumption in this dose range [25]. Therefore, presumably MPD would not reduce motivation for a food reward.…”

Section: Discussionmentioning

confidence: 92%

Methylphenidate improves performance on the radial arm maze in periadolescent rats

Dow-Edwards

Weedon

Hellmann

2008

Neurotoxicology and Teratology

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Methylphenidate (Ritalin; MPD) is one of the most commonly prescribed drugs in childhood and adolescence and many clinical studies have documented its efficacy. Due to the limitations of conducting invasive research in humans, animal models can be beneficial for studying drug effects. However, few animal studies have demonstrated the effects of methylphenidate on cognitive processes. The objective of this study was to find a dose of methylphenidate that was effective in improving performance on a spatial working memory cognitive task when administered orally to periadolescent rats. Therefore, we dosed subjects with methylphenidate at 1 or 3 mg/kg/day via gastric intubation from postnatal day 22 to 59 and assessed the effects of the drug on performance on the radial arm maze each day. To enhance performance overall, a second experiment was conducted where the subjects were moderately food restricted (to 90% of the free-feeding weight). Results of Experiment 1 show that during the first week of testing only the 3mg/kg MPD-treated males showed improved performance (entries prior to repeated entry) when ad-lib fed and housed in pairs while the same dose significantly improved performance in both males and females under conditions of food-restriction and individual housing in Experiment 2. MPD also produced a pattern of increased errors and arms entered during the first week, especially in Experiment 2. MPD increased locomotor activity when tested at postnatal day 60 in both experiments. The data suggest that 3mg/ kg oral methylphenidate improves performance on a spatial cognitive task only early in treatment in the rat. While males show improvement under conditions of both high and low motivation, females only show MPD effects when highly motivated. Hypothetically, methylphenidate may improve radial arm maze performance through increased attention and improved spatial working memory and/or alterations in locomotion, reactivity to novelty or anxiety. Regardless, the study supports the utility of the rat as a suitable model to examine the effects of low dose oral MPD.

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“…Na toxicidade aguda pré-clínica, os sinais de toxicidade sistêmica são definidos considerando a redução na massa corporal, além da redução do desenvolvimento ponderal dos animais experimentais (Tofovic e Jackson 1999;Raza et al 2002;Teo et al 2002). Outros sinais de toxicidade podem se expressar pela alteração da massa relativa dos órgãos, alterações hematológicas e bioquímicas sanguíneas (Gonzalez e Silva 2003).…”

Section: Discussionunclassified

Avaliação da toxicidade aguda pré-clínica do extrato metanólico das cascas do caule de Parahancornia amapa (Apocynaceae)

et al. 2016

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RESUMOParahancornia amapa é uma espécie endêmica do Estado do Amapá, na região Amazônica. Este estudo teve como objetivo avaliar a toxicidade aguda do extrato metanólico das cascas do caule de P. amapa. Diferentes concentrações do extrato foram adicionadas aos camarões de salmoura (Artemia salina) e a concentração letal média (CL 50 Preclinical acute toxicological evaluation of the methanolic stem bark extract of Parahancornia amapa (Apocynaceae)ABSTRACT Parahancornia amapa is an endemic plant species of Amapá in the Amazon region. This study aimed to evaluate the acute toxicity of methanol extract of the bark of P. amapa. Different concentrations of the extract were added to the brine shrimps (Artemia salina) and 50% lethality concentration (LC 50 ) was assessed. The results of the brine-shrimp assay indicated that the extract was found to be non-toxic. Acute toxicity was studied in Wistar rats (males and females) after single dose (2000 mg kg -1 ) by oral gavage. Food and water intake, body weight, general behavioral changes and mortality of animals were noted. Blood samples were collected for haematological and serum biochemical parameters measurements. Subsequently, they were euthanized and their organs (heart, kidneys, liver and lungs) subjected to macroscopic and histopathological analysis. There was no mortality or any sign of behavioral change or toxicity observed after oral administration of the extract. Nevertheless, it was observed a significant increase (p<0.05) on water intake of female rats treated with the extract of P. amapa (127.64 mL) when compared to control group (101.93 mL). A significant increase (p<0.05) in platelet count was also observed in both male (288.00x10 3 mm 3 ) and female (220.83x10 3 mm 3 ) rats that received the extract when compared to their respective control groups (128.33x10 3 mm 3 ; 109.50x10 3 mm 3 ). Histopathological changes were not related to the treatment with extract in any of the analyzed organs. These results suggest that P. amapa extract has a non-toxic effect.

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A 90-day oral gavage toxicity study of d-methylphenidate and d,l-methylphenidate in Sprague–Dawley rats

Cited by 311 publications

References 14 publications

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats

Effect of essential oil from Citrus aurantium in maternal reproductive outcome and fetal anomaly frequency in rats

Methylphenidate improves performance on the radial arm maze in periadolescent rats

Avaliação da toxicidade aguda pré-clínica do extrato metanólico das cascas do caule de Parahancornia amapa (Apocynaceae)

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