The Effects of Riluzole on Cisplatin-induced Ototoxicity

Abstract Introduction Riluzole (2-amino-6-trifluoromethoxy benzothiazole) is known as a neuroprotective, antioxidant, antiapoptotic agent. It may have beneficial effects on neuronal cell death due to cisplatin-induced ototoxicity. Objective To evaluate the effect of riluzole on cisplatin-induced ototoxicity in guinea pigs. Methods Twenty-four guinea pigs, studied in three groups, underwent auditory brainstem response evaluation using click and 8 kHz tone burst stimuli. Subsequently, 5 mg/kg of cisplatin were administered to all animals for 3 days intraperitoneally (i.p.) to induce ototoxicity. Half an hour prior to cisplatin, groups 1, 2 and 3 received 2 ml of saline i.p., 6 mg/kg of riluzole hydrochloride i.p., and 8 mg/kg of riluzole hydrochloride i.p., respectively, for 3 days. The auditory brainstem responses were repeated 24 hours after the last drug administration. The cochleae were analyzed by transmission electron microscopy (TEM). Results After drug administiration, for 8,000 Hz stimulus, group 1 had significantly higher threshold shifts when compared with groups 2 (p < 0.05) and 3 (p < 0.05), and there was no significant difference in threshold shifts between groups 2 and 3 (p > 0.05). Transmission electron microscopy findings demonstrated the protective effect of riluzole on the hair cells and the stria vascularis, especially in the group treated with 8 mg/kg of riluzole hydrochloride. Conclusion We can say that riluzolemay have a protective effect on cisplatin- induced ototoxicity. However, additional studies are needed to confirm these results and the mechanisms of action of riluzole.

Neuroprotective effect of vitamin c against ptz induced apoptotic neurodegeneration in adult rat brain

The present study was designed to observe the effect of PTZ on expression of caspsae-3, and to evaluate the neuroprotective role of vitamin C [vit-C] against PTZ-induced apoptotic neurodegeneration in adult rat brain. We observed that administration of a single conclusive dose of pentylenetetrazol [PTZ 50mg/kg] in adults rats induced epileptic seizure and increased activation of caspase-3 and caused neuronal death. Further, rats were injected with vit-C [250 mg/kg] 30 min before PTZ injection. The protective effect of vit-C against PTZ-induced apoptotic neurodegeneration in adult rat brain was observed using Western blot analysis and Nissl staining. The results showed that conclusive dose of PTZ-induced seizure, increased expression of caspase-3 and neuronal apoptosis in adult rat brain. Whereas, the pretreatment of vit-C along with PTZ showed significantly decreased expression of caspase-3 as compare to control group. Finally, our results indicated that vit-C can prevent some of the deleterious effect of seizure and neuronal degeneration induced by PTZ in adult rat brain

Intoxicação experimental por Aspergillus clavatus em ovinos / Experimental poisoning by Aspergillus clavatus in sheep

Descreve-se a reprodução experimental de doença neurológica em ovinos através da administração de bagaço de malte (resíduo cervejaria) contaminado com Aspergillus clavatus. Esse resíduo de cervejaria, cujas amostras revelaram cultura pura de A. clavatus, estava sendo utilizado em duas propriedades, onde ocorreram surtos da doença em bovinos. Os sinais clínicos iniciaram-se cerca de 2 a 6 dias após a administração do subproduto ou da cultura e a evolução clínica foi de 1,5 a 12 dias. Os sinais clínicos, que foram predominantemente locomotores e respiratórios, incluíram tremores musculares, hiperestesia, taquipnéia progressiva, rigidez de membros pélvicos (mais evidente à locomoção), fraqueza dos posteriores e decúbito. Um ovino também apresentou apoio ocasional sobre os boletos dos membros pélvicos. As anormalidades locomotoras e tremores eram intensificados pelo exercício. Entretanto, em 6 dos 7 ovinos, o apetite e a dipsia eram mantidas até próximo à morte ou eutanásia. O principal achado histológico consistia de degeneração e necrose neuronal cromatolítica em núcleos nervosos específicos do tronco encefálico, cornos ventrais da medula espinhal e gânglios espinhais, trigeminal, estrelado e celíaco. Três ovinos também apresentaram degeneração e necrose leves em músculos dos membros pélvicos e torácicos.

This paper describes the experimental reproduction of a neurological condition in sheep by the administration of a beer by-product contaminated with Aspergillus clavatus. Samples of this by-product, in which pure cultures of A. clavatus grew, originated from two farms where outbreaks of A. clavatus poisoning in cattle had occurred. The onset of symptomatology was 2 to 6 days after dosage with the contaminated beer by-product or pure A. clavatus culture. The clinical course lasted from one and a half to 12 days. Clinical signs were predominantly of locomotor and respiratory nature and included muscle tremors, hyperesthesia, and progressive tachypnea, rigidity of the pelvic limbs, posterior weakness, and recumbency. One sheep also showed occasional knuckling of fetlocks of the hind limbs. Gait abnormalities and tremors were more pronounced after exercise. In 6 of 7 sheep, appetite and dypsia were maintained until close to death or euthanasia. The main histological findings consisted of chromatolytic neuronal degeneration and necrosis in selected nuclei of the brain stem, the ventral horn of the spinal cord and the spinal, trigeminal, stellate and celiac ganglions. Three sheep also presented slight degenerative and necrotic changes in muscles of the pelvic and thoracic limbs.

Intoxicação espontânea por vagens de Prosopis juliflora (Leg. Mimosoideae) em bovinos no Estado de Pernambuco / Spontaneous poisoning in cattle by mesquite beans, Prosopis juliflora (Leg. Mimosoideae) in Pernambuco

Descrevem-se três surtos de intoxicação por vagens de Prosopis juliflora no Sertão e Agreste de Pernambuco, na região semi-árida, em animais pastejando áreas invadidas pela planta ou que ingeriram as vagens como alimento concentrado. Em duas fazendas nas que a doença ocorria esporadicamente foram observados casos individuais. Em outra, o surto afetou um rebanho de 1206 bovinos, dos quais adoeceram 112 (9,28 por cento) e morreram 84 (6,96 por cento), enquanto os demais 28 (2,32 por cento) recuperaram-se e ganharam peso após a retirada das vagens da alimentação. Clinicamente observou-se, principalmente, perda de peso progressiva, atrofia da musculatura da face e masseter, mandíbula pendulosa, protrusão de língua, dificuldade de apreensão e mastigação dos alimentos, torção da cabeça para mastigar ou ruminar, salivação excessiva, disfagia e hipotonia lingual. Nos exames laboratoriais constatou-se anemia e hipoproteinemia. Na necropsia havia caquexia e diminuição de volume e coloração acinzentada dos músculos masseteres. Na histologia observou-se degeneração de neurônios do núcleo motor do trigêmeo, degeneração Walleriana do nervo trigêmeo e atrofia muscular por denervação do músculo masseter com substituição por tecido fibroso. Recomendam-se medidas para a profilaxia da intoxicação e discute-se a necessidade de desenvolver pesquisas para determinar a viabilidade econômica e sustentabilidade da utilização da algaroba como alimento animal ou humano e para produção de carvão, lenha ou madeira.

Three outbreaks of poisoning by Prosopis juliflora pods are reported in the semiarid region of the state of Pernambuco, Northeastern Brazil, in cattle grazing in fields invaded by the plant or ingesting mesquite beans as a concentrate food. In two farms the disease occurred sporadically. In another, 112 (9.28 percent) cattle out of 1206 were affected, 84 (6.96 percent) died due to emaciation, and 28 (2.32 percent) gained weight after the pods had been withdrawn from the feed. Main clinical signs were progressive weight loss, atrophy of the masseter muscles, dropped jaw, tongue protrusion, difficulties in prehending food, tilting the head during mastigation or rumination, salivation, impaired swallowing, and decreased tone of the tongue. The hematology reveals hypoproteinemia and anemia. Gross lesions were emaciation and reduction in size of the masseter muscles, which appear thinner than normal and grayish due muscular atrophy. Degeneration of neurons of the trigeminal motor nuclei, Wallerian degeneration of the trigeminal nerve roots, and muscular atrophy of the masseter muscles with substitution by fibrous tissue were observed on histologic examination. For the prevention of the poisoning is necessary to limit the amount of mesquite beans in animal nutrition. It is also necessary to develop research to determine the economic and sustainability of the use of Prosopis juliflora for animal food, human food or other uses such as charcoal, wood and fuel wood.

Understanding safety of glutamate in food and brain.

Glutamate is ubiquitous in nature and is present in all living organisms. It is the principal excitatory neurotransmitter in central nervous system. Glutamate is being used as food additive for enhancing flavour for over last 1200 years imparting a unique taste known as "umami" in Japanese. It is being marketed for about last 100 years. The taste of umami is now recognized as the fifth basic taste. Many of the foods used in cooking for enhancing flavour contain high amount of glutamate. Breast milk has the highest concentration of glutamate amongst all amino acids. Glutamate in high doses as gavage or parenteral injection have been reported to produce neurodegeneration in infant rodents. The neurodegeneration was not produced when gluamate was given with food. The Joint FAO/WHO Expert Committee on Food Additives, based on enumerable scientific evidence, has declared that, "glutamate as an additive in food" is not an health hazard to human being. Glutamate is used as signaling molecule not only in neuronal but also in non-neuronal tissues. Excessive accumulation of glutamate in the synaptic cleft has been associated with excitotoxicty and glutamate is implicated in number of neurological disorders. Excessive accumulation could be attributed to increase release, failure of transport system for uptake mechanism, neuronal injury due to hypoxia-ischemia, trauma and associated metabolic failures. The role blood brain barrier, vesicular glutamate and sodium dependent excitatory amino acid transporters in glutamate homeostasis are emphasized in the review.

Consideraciones sobre las complicaciones motoras y neurotoxicidad de la levodopa en la enfermedad de Parkinson / Motor complications and neurotoxicity associated with levodopa use in Parkinson disease

Desde la introducción de la levodopa para el manejo de la enfermedad de Parkinson ésta ha sido el tratamiento estándar de esta enfermedad. La aparición de fármacos alternativos como los agonistas dopaminérgicos abrieron un debate acerca de los potenciales beneficios de estas terapias por sobre levodopa y los eventuales efectos deletéreos de esta última. En este artículo se actualiza la información acerca de las complicaciones motoras y de neurotoxicidad inducidas por levodopa.