Molecular mechanisms underlying ameliorative impact of melatonin against age-dependent chronic arsenic toxicity in rats' brains.

Accumulation of random molecular damage such as oxidative DNA damage and inflammation is extremely found to be involved in the aging process. Due to extreme energy requirements and high lipid levels, the brain is more susceptible to oxidative damage during aging especially under exposure to toxic elements such as arsenic. Therefore, this study was aimed to evaluate the ameliorative effects of melatonin, as a neurohormone, on the arsenic-induced behavioral abnormalities, and the underlying mechanisms. Forty-eight rats, as young and old aged groups were exposed to 5.55 g/kg body weight arsenic for 4 weeks and then 10 mg/kg melatonin for 2 weeks. Our results showed that arsenic led to anxiety-like behavioral abnormalities in rats. Increased oxidative stress-induced damage to DNA, lipids and proteins, decreased potential of antioxidant defense system, induced apoptosis, elevated inflammation, and alteration in the histology of cortical region of brains are observed in the rats exposed to arsenic. These effects were more prominent in aged rats in comparison to young rats. Melatonin successfully attenuates arsenic induced adverse effects on the brain in both age groups. In conclusion, our study shows that melatonin has significant ameliorative impact on age-dependent cytotoxicity of arsenic in rats' brains.

Detailed Analysis of Neurological Symptoms and Sensory Disturbances Due to Chronic Arsenic Exposure in Toroku, Japan.

As a result of population growth and the development of tube wells, humans' exposure to arsenic has increased over the past few decades. The natural course of organ damage secondary to arsenic exposure is not yet well understood. In Toroku, Japan, an arsenic mine was intermittently operated from 1920 to 1962, and residents were exposed to high concentrations of arsenic. In this paper, we analyzed 190 consecutive residents for whom detailed records of neurological symptoms and findings were obtained from 1974 to 2005. All participants were interviewed regarding the presence of general, skin, hearing, respiratory, and neurological symptoms. Neurological symptoms were classified into extremity numbness or pain, constipation, dyshidrosis, sensory loss, and muscle atrophy. Superficial and vibratory sensation was also evaluated. More than 80% of participants experienced extremity numbness, and numbness was the most common neurological symptom. Numbness was associated with superficial sensory disturbance, and was correlated with the subsequent development of other neurological symptoms, including autonomic and motor symptoms. No previous studies have investigated the natural course of chronic arsenic intoxication; thus, these data serve as a guide for detecting early symptoms due to arsenic exposure.

Subacute Arsenic Neuropathy: Clinical and Electrophysiological Observations.

We report a patient who developed subacute peripheral neuropathy following ingestion of a traditional medicine for obesity. A 9-year-old girl who had a residual equinus varus deformity and sphincter disturbance due to pelvic ganglioneuroma presented with subacute sensorimotor peripheral neuropathy of 2 weeks duration. Her symptoms started 3 weeks after she started taking a locally made traditional medicine for obesity. She had no other systemic features of arsenic toxicity. She had Mee's lines on her nails and high serum arsenic levels and 24-hour urine levels confirmed the diagnosis of arsenic neuropathy. Nerve conduction study on admission demonstrated axonal sensorimotor neuropathy with slowed conduction velocity. She was not given any specific treatment and recovery was slow. At 18 months, she showed complete recovery and electrodiagnostic parameters returned to normal values. Arsenic is a known ingredient of many Indian ethnic remedies and possibility of arsenic neuropathy should be thought of in patients presenting with acute or sub-acute peripheral neuropathy of unknown etiology.

On the Use of Hair Analysis for Assessing Arsenic Intoxication.

Correlations between the concentrations of arsenic in scalp hair and in drinking water as well as in blood and/or urine have been reported. These correlations clearly show exposure⁻absorption⁻excretion relationships. In addition, arsenic metabolites such as monomethylarsonic acid and dimethylarsinic acid have been identified and quantified in these tissues and fluids, leaving little doubt that elevated levels of arsenic in the hair can reflect systemic arsenic intoxication. Consequently, hair analysis has potential merit as a screening procedure for poisoning by arsenic. However, questions regarding the exogenous versus the endogenous deposition of arsenic in the hair, and uncertainties about the normal level of arsenic in the hair remain unresolved. Pending their resolution, the determination of arsenic in hair should remain a screening tool, and clinical signs and symptoms should be employed to complete the diagnosis of arsenic poisoning.

Assessment of the Effects of Graded Doses of Polyphenolic-Rich Fraction of Garcinia kola Seeds on Pituitary-Testicular Axis of Male Wistar Rats.

This study evaluated the ameliorative and prophylactic effects of 2 different doses of polyphenolic-rich fraction of Garcinia kola (PPRFGk) seeds on the histology and hormones of pituitary-testicular axis of male Wistar rats. Thirty-five male Wistar rats (150-200 g) were divided into 7 groups of 5 rats each. Groups I and II were given distilled water (0.5 mL/day) for 8 days followed by propylene glycol (0.2 mL/d) and 600 mg/kg of PPRFGk, respectively, for 21 days. Group III received sodium arsenate (8 days), left untreated for 21 days. Groups IV and V received sodium arsenate (20 mg/kg) for 8 days followed by PPRFGk (300 and 600 mg/kg, respectively) for 21 days. Groups VI and VII received PPRFGk (300 and 600 mg/kg, respectively) for 21 days followed by sodium arsenate (20 mg/kg) for 8 days. Rats were killed by cervical dislocation 24 hours after the last dose and their blood collected through cardiac puncture. Blood sera were assayed for the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone using immunoassay techniques. Histology of the pituitary gland and testes was carried out. A significant reduction was observed in the concentration of FSH in groups IV, V, VI, and VII in comparison with groups I and II. The concentrations of both LH and testosterone showed significant decreases in groups IV, V, VI, and VII in comparison with group I. Group III presented with the lowest serum hormonal concentrations. Photomicrographs of the pituitary gland revealed greatly reduced basophils in group III and mildly reduced basophils in groups IV, VI, and VII in comparison with groups I and II. Group V revealed hypercellularized and distorted basophils. Photomicrographs of the testes showed detachment of the seminiferous tubules from the basement membrane and disruption of the interstitial space which was worse in group III, moderate in groups V and VI, and mild in group VII. In conclusion, PPRFGk effected a dose-dependent reversal and prevention of the perturbations caused by arsenate in rats.

O problema da dose em homeopatia: avaliação do efeito de altas diluições de arsenicum album 30ch em ratos intoxicados com arsênico / The problem of dose in homeopathy: evaluation of the effect of high dilutions of Arsenicum album 30cH on rats intoxicated with arsenic

Background: Although scientific studies have confirmed the action of homeopathic high dilutions in living organisms an endless debate on the choice of the most fitting dilution, the frequency of administration and the dose (amount of medicine) still remains. Aims: This study sought to assess the in vivo effect of 2 different concentrations of Arsenicum album 30cH in order to elucidate some problems in the homeopathic notion of dose. Methods: Male Wistar rats previously intoxicated with sodium arsenate by peritoneal injection were treated with undiluted Ars 30cH and Ars 30cH in 1% solution administered by oral route. Atomic absorption spectroscopy was employed to measure the levels of arsenic retained in the animals as well as the amounts eliminated through urine. Urine samples were collected before and after and during treatment. A positive control group (intoxicated animals) and negative control group (nonintoxicated animals) were administered only the vehicle used to prepare the medicine (ethanol). Results: The groups treated with undiluted Ars 30cH and Ars 30cH in 1% solution eliminated significant amounts of arsenic through urine when compared to the control groups. The group treated with undiluted Ars 30cH eliminated significantly higher amounts of arsenic than the group treated with the same medicine in 1% solution. Conclusion: These results suggest that undiluted Ars 30cH was more effective than in 1% solution in this experimental model.(AU)

Background: Although scientific studies have confirmed the action of homeopathic high dilutions in living organisms an endless debate on the choice of the most fitting dilution, the frequency of administration and the dose (amount of medicine) still remains. Aims: This study sought to assess the in vivo effect of 2 different concentrations of Arsenicum album 30cH in order to elucidate some problems in the homeopathic notion of dose. Methods: Male Wistar rats previously intoxicated with sodium arsenate by peritoneal injection were treated with undiluted Ars 30cH and Ars 30cH in 1% solution administered by oral route. Atomic absorption spectroscopy was employed to measure the levels of arsenic retained in the animals as well as the amounts eliminated through urine. Urine samples were collected before and after and during treatment. A positive control group (intoxicated animals) and negative control group (nonintoxicated animals) were administered only the vehicle used to prepare the medicine (ethanol). Results: The groups treated with undiluted Ars 30cH and Ars 30cH in 1% solution eliminated significant amounts of arsenic through urine when compared to the control groups. The group treated with undiluted Ars 30cH eliminated significantly higher amounts of arsenic than the group treated with the same medicine in 1% solution. Conclusion: These results suggest that undiluted Ars 30cH was more effective than in 1% solution in this experimental model.(AU)

The problem of dose in homeopathy: evaluation of the effect of high dilutions of Arsenicum album 30cH on rats intoxicated with arsenic / O problema da dose em homeopatia: avaliação do efeito de altas diluições de Arsenicum album 30cH em ratos intoxicados com arsênico / El problema de la dosis en homeopatía: evaluación del efecto de altas diluciones de Arsenicum album 30cH en ratones intoxicados con arsénico

Background: Although scientific studies have confirmed the action of homeopathic high dilutions in living organisms an endless debate on the choice of the most fitting dilution, the frequency of administration and the dose (amount of medicine) still remains. Aims: This study sought to assess the in vivo effect of 2 different concentrations of Arsenicum album 30cH in order to elucidate some problems in the homeopathic notion of dose. Methods: Male Wistar rats previously intoxicated with sodium arsenate by peritoneal injection were treated with undiluted Ars 30cH and Ars 30cH in 1% solution administered by oral route. Atomic absorption spectroscopy was employed to measure the levels of arsenic retained in the animals as well as the amounts eliminated through urine. Urine samples were collected before and after and during treatment. A positive control group (intoxicated animals) and negative control group (non-intoxicated animals) were administered only the vehicle used to prepare the medicine (ethanol). Results: The groups treated with undiluted Ars 30cH and Ars 30cH in 1% solution eliminated significant amounts of arsenic through urine when compared to the control groups. The group treated with undiluted Ars 30cH eliminated significantly higher amounts of arsenic than the group treated with the same medicine in 1% solution. Conclusion: These results suggest that undiluted Ars 30cH was more effective than in 1% solution in this experimental model.

Introdução: embora estudos científicos têm confirmado a ação das altas diluições homeopáticas em organismos vivos, permanece o debate infindável acerca da escolha da diluição mais adequada, a frequência de administração e a dose (quantidade de medicamento). Objetivos: este estudo procurou avaliar o efeito in vitro de 2 concentrações diferentes de Arsenicum album 30cH a fim de elucidar alguns aspectos da noção homeopática de dose. Métodos: ratos Wistar machos previamente intoxicados com arseniato de sódio por injeção peritoneal foram tratados com Ars 30cH não diluído ou diluído 1% por via oral. Foi utilizada espectroscopia de absorção atômica para medir os níveis de arsênico retido no organismo e eliminado através da urina. As amostras de urina foram colhidas antes, após e durante o tratamento. Os grupos controle positivo (animais intoxicados) e negativo (animais não intoxicados) receberam apenas o veículo utilizado para preparar o medicamento (etanol). Resultados: os grupos tratados com Ars 30cH não diluído e diluído em solução 1% eliminaram quantidades significativamente maiores de arsênico através da urina por comparação aos grupos controle. O grupo tratado com Ars 30cH não diluído eliminou quantidades significativamente maiores de arsênico que o grupo tratado com o mesmo medicamento em solução 1%. Conclusão: esses resultados sugerem que Ars 30cH não diluído foi mais efetivo que a solução 1% do mesmo neste modelo experimental.

Introducción: aunque estudios científicos han confirmado la acción de las altas diluciones homeopáticas en organismos vivos, permanece sin resolver la discusión acerca de la elección de la dilución más adecuada, la frecuencia de administración y la dosis (cantidad de medicamento). Objetivos: este estudio buscó evaluar el efecto in vitro de 2 concentraciones diferentes de Arsenicum album 30cH para dirimir algunos problemas en la noción homeopática de dosis. Métodos: ratones Wistar macho previamente intoxicados con arseniato de sodio por inyección peritoneal fueron tratados con Ars 30cH sin diluir o diluido en solución 1% por vía oral. Fue utilizada espectroscopía de absorción atómica para medir los niveles de arsénico retenidos en el organismo y eliminados por orina. Las muestras de orina fueron recogidas antes, durante y después del tratamiento. Los grupos control positivo (animales intoxicados) y negativo (animales no intoxicados) recibieron exclusivamente el vehículo utilizado para preparar el medicamento (etanol). Resultados: los grupos tratados con Ars 30cH no diluido y diluido 1% eliminaron cantidades significativamente mayores de arsénico por orina que los controles. El grupo tratado con Ars 30cH no diluido eliminó cantidades significativamente mayores de arsénico por orina que el grupo tratado con el mismo medicamento diluido 1%. Conclusión: estos resultados sugieren que Ars 30cH no diluido fue más efectivo que cuando diluido 1% en este modelo experimental.

The problem of dose in homeopathy: evaluation of the effect of high dilutions of Arsenicum album 30cH on rats intoxicated with arsenic / O problema da dose em homeopatia: avaliação do efeito de altas diluições de Arsenicum album 30cH em ratos intoxicados com arsênico / El problema de la dosis en homeopatía: evaluación del efecto de altas diluciones de Arsenicum album 30cH en ratones intoxicados con arsénico

Background: Although scientific studies have confirmed the action of homeopathic high dilutions in living organisms an endless debate on the choice of the most fitting dilution, the frequency of administration and the dose (amount of medicine) still remains. Aims: This study sought to assess the in vivo effect of 2 different concentrations of Arsenicum album 30cH in order to elucidate some problems in the homeopathic notion of dose. Methods: Male Wistar rats previously intoxicated with sodium arsenate by peritoneal injection were treated with undiluted Ars 30cH and Ars 30cH in 1% solution administered by oral route. Atomic absorption spectroscopy was employed to measure the levels of arsenic retained in the animals as well as the amounts eliminated through urine. Urine samples were collected before and after and during treatment. A positive control group (intoxicated animals) and negative control group (non-intoxicated animals) were administered only the vehicle used to prepare the medicine (ethanol). Results: The groups treated with undiluted Ars 30cH and Ars 30cH in 1% solution eliminated significant amounts of arsenic through urine when compared to the control groups. The group treated with undiluted Ars 30cH eliminated significantly higher amounts of arsenic than the group treated with the same medicine in 1% solution. Conclusion: These results suggest that undiluted Ars 30cH was more effective than in 1% solution in this experimental model.(AU)

Introdução: embora estudos científicos têm confirmado a ação das altas diluições homeopáticas em organismos vivos, permanece o debate infindável acerca da escolha da diluição mais adequada, a frequência de administração e a dose (quantidade de medicamento). Objetivos: este estudo procurou avaliar o efeito in vitro de 2 concentrações diferentes de Arsenicum album 30cH a fim de elucidar alguns aspectos da noção homeopática de dose. Métodos: ratos Wistar machos previamente intoxicados com arseniato de sódio por injeção peritoneal foram tratados com Ars 30cH não diluído ou diluído 1% por via oral. Foi utilizada espectroscopia de absorção atômica para medir os níveis de arsênico retido no organismo e eliminado através da urina. As amostras de urina foram colhidas antes, após e durante o tratamento. Os grupos controle positivo (animais intoxicados) e negativo (animais não intoxicados) receberam apenas o veículo utilizado para preparar o medicamento (etanol). Resultados: os grupos tratados com Ars 30cH não diluído e diluído em solução 1% eliminaram quantidades significativamente maiores de arsênico através da urina por comparação aos grupos controle. O grupo tratado com Ars 30cH não diluído eliminou quantidades significativamente maiores de arsênico que o grupo tratado com o mesmo medicamento em solução 1%. Conclusão: esses resultados sugerem que Ars 30cH não diluído foi mais efetivo que a solução 1% do mesmo neste modelo experimental.(AU)

Introducción: aunque estudios científicos han confirmado la acción de las altas diluciones homeopáticas en organismos vivos, permanece sin resolver la discusión acerca de la elección de la dilución más adecuada, la frecuencia de administración y la dosis (cantidad de medicamento). Objetivos: este estudio buscó evaluar el efecto in vitro de 2 concentraciones diferentes de Arsenicum album 30cH para dirimir algunos problemas en la noción homeopática de dosis. Métodos: ratones Wistar macho previamente intoxicados con arseniato de sodio por inyección peritoneal fueron tratados con Ars 30cH sin diluir o diluido en solución 1% por vía oral. Fue utilizada espectroscopía de absorción atómica para medir los niveles de arsénico retenidos en el organismo y eliminados por orina. Las muestras de orina fueron recogidas antes, durante y después del tratamiento. Los grupos control positivo (animales intoxicados) y negativo (animales no intoxicados) recibieron exclusivamente el vehículo utilizado para preparar el medicamento (etanol). Resultados: los grupos tratados con Ars 30cH no diluido y diluido 1% eliminaron cantidades significativamente mayores de arsénico por orina que los controles. El grupo tratado con Ars 30cH no diluido eliminó cantidades significativamente mayores de arsénico por orina que el grupo tratado con el mismo medicamento diluido 1%. Conclusión: estos resultados sugieren que Ars 30cH no diluido fue más efectivo que cuando diluido 1% en este modelo experimental.(AU)