ABSTRACT
ABSTRACT Purpose: As a class of psychostimulant drugs, amphetamines are widely abused for their stimulant, euphoric, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Following the onset of these effects, 3,4 methylenedioxymethamphetamine produces persistent damage to dopamine and serotonin nerve terminals, resulting in long-lasting neurotoxicity. The purpose of this investigation was to assess the effects of treatment with low dose of methylenedioxymethamphetamine on retinal function of C57BL/6 mice and its underlying mechanisms. Methods: C57BL/6 mice were divided randomly into two groups (n=10): one group was treated with phosphate buffered saline by intraperitoneal injection daily; the other group was treated with 1 mg/kg methylenedioxymethamphetamine by intraperitoneal injection daily for three months. Electroretinography was used to test retinal function every month. H&E staining and terminal deoxynucleotidyl transferase assay were used to evaluate the retinal morphology and histology. Enzyme-linked immunosorbent assay assays were used to measure markers of oxidative stress and inflammatory factors. Gene and protein expression was detected by real-time PCR and western blot. Results: Three-month treatment with methylenedioxymethamphetamine induced significant retinal dysfunction via photoreceptor cell apoptosis by oxidative stress and inflammatory responses. Conclusions: These results suggest that long-term treatment with methylenedioxymethamphetamine increases inflammatory responses in photoreceptor cells resulting in retinal dysfunction in C57BL/6 mice. Thus, this investigation provides preclinical rationale for the retina damage caused by the methylenedioxymethamphetamine abuse.
RESUMO Objetivos: Como uma classe de drogas psicoesti mulantes, as anfetaminas são amplamente usadas por suas propriedades estimulantes, eufóricas e alucinógenas. Muitos desses efeitos resultam de aumentos agudos na neurotransmissão da dopamina e da serotonina. Após o início desses efeitos, a 3,4-metilenedioximetanfetamina produz danos persistentes nos terminais nervosos de dopamina e serotonina, resultando em neurotoxicidade duradoura. O objetivo desta investigação foi avaliar os efeitos do tratamento baixa dose de metilenedioximetanfetamina na função da retina em camundongos C57BL/6 e seus mecanismos subjacentes. Métodos: Camundongos C57BL/6 foram divididos aleatoriamente em dois grupos (n=10): um grupo foi tratado com solução salina tamponada de fosfato por injeção intraperitoneal diária; o outro grupo foi tratado com 1 mg/kg de metilenedioximetanfetamina por injeção intraperitoneal diária durante 3 meses. Eletroretinografia foi utilizada para testar a função da retina a cada mês. A coloração H&E e análise com deoxinucleotidil terminal transferase foram utilizados para avaliar a morfologia e histologia da retina. Testes de imunoabsorção enzimática foram utilizados para medir marcadores de estresse oxidativo e fatores inflamatórios. A expressão de genes e proteínas foi detectada por PCR em tempo real e western blot. Resultados: O tratamento de três meses com metilenedioximetanfetamina induziu disfunção de retina significativa por apoptose de células fotorreceptoras por estresse oxidativo e resposta inflamatória. Conclusões: Estes resultados sugerem que o tratamento a longo prazo com metilenedioximetanfetamina aumenta as respostas inflamatórias em células fotorreceptoras, resultando em disfunção de retina em camundongos C57BL/6. Assim, a investigação foence uma justificação pré-clínica para os danos na retina causados pelo abuso de metilenedioximetanfetamina.
Subject(s)
Animals , Rats , Retinal Degeneration/drug therapy , Eye Injuries/drug therapy , N-Methyl-3,4-methylenedioxyamphetamine/toxicity , Retinal Degeneration/genetics , Eye Injuries/genetics , Blotting, Western , Apoptosis/drug effects , Oxidative Stress/drug effects , Electroretinography , Mice, Inbred C57BLABSTRACT
ABSTRACT Purpose: Nitrogen mustard (NM) is a devastating casualty agent in chemical warfare. There is no effective antidote to treat NM-induced ocular injury. We aimed to assess the effects of proanthocyanidin (PAC) and coenzyme Q10 (CoQ10) on NM-induced ocular injury. Methods: Eighteen male rats were divided into the following 4 groups: NM, NM + PAC, NM + CoQ10, and control. The 3 NM groups received a single dose of NM (0.02 mg/μL) on the right eye to induce ocular injury. The control group received saline only. Thirty minutes after the application of NM, the NM + PAC group received PAC (100 mg/kg) via gastric gavage, while the NM + CoQ10 group received CoQ10 (10 mg/kg) via intraperitoneal injection. PAC and CoQ10 were administered once a day for 5 consecutive days. The rats were then sacrificed. Macroscopic images of the eyes were examined and eye tissues were collected for histology. Results: The treatment groups were compared to the control group with regard to both corneal opacity and lid injury scores. The findings were not significantly different for both the NM + PAC and NM + CoQ10 groups. In both the NM + PAC and NM + CoQ10 groups, the histological changes seen in the NM group demonstrated improvement. Conclusions: Our results indicate that PAC and CoQ10 treatments have therapeutic effects on NM-induced ocular injury in a rat model. PAC and CoQ10 may be novel options in patients with NM-induced ocular injury.
RESUMO Objetivo: A mostarda de nitrogênio (MN) é um agente de guerra química devastador. Não existe um antídoto eficaz para tratar lesões oculares induzidas por MN. Nosso objetivo foi avaliar os efeitos da proantocianidina (PAC) e da coenzima Q10 (CoQ10) na lesão ocular induzida por MN. Métodos: Dezoito ratos machos foram divididos em 4 grupos: MN, MN + PAC, MN + CoQ10 e Controle. Três grupos receberam uma dose única de MN (0,02 mg/μL) destilada no olho direito para gerar lesão ocular. Os animais do grupo controle receberam apenas solução salina. Trinta minutos após a aplicação de MN nos animais, o grupo MN + PAC recebeu PAC (100 mg/kg) por gavagem gástrica, enquanto a CoQ10 (10 mg/kg) foi administrada ao grupo MN + CoQ10 por meio de injeção intraperitoneal. A administração de PAC e de CoQ10 foi realizada uma vez por dia, durante 5 dias consecutivos. Os ratos foram, então, sacrificados. Imagens macroscópicas dos olhos foram examinadas e tecidos oculares foram coletados para histologia. Resultados: Os grupos de tratamento foram comparados ao grupo de controle quanto à opacidade da córnea e quanto aos escores de lesão da cobertura da córnea. Os resultados foram insignificantes para ambos os grupos. Ambos, o grupo MN+PAC e o grupo MN+CoQ10, apresentaram melhoras das alterações histológicas observadas no grupo MN. Conclusões: Nossos resultados indicam que os tratamentos com PAC e com CoQ10 têm efeitos terapêuticos sobre lesões oculares induzidas por MN em um modelo em ratos. A proantocianidina e a CoQ10 podem ser uma nova opção nesses casos.
Subject(s)
Animals , Male , Rats , Burns, Chemical/drug therapy , Eye Injuries/drug therapy , Ubiquinone/analogs & derivatives , Proanthocyanidins/therapeutic use , Antioxidants/therapeutic use , Random Allocation , Chemical Warfare Agents , Eye Injuries/chemically induced , Ubiquinone/therapeutic use , Rats, Sprague-Dawley , Disease Models, Animal , MechlorethamineABSTRACT
Traumatic head injury is a leading cause of mortality and morbidity. As a result of head trauma occurring in the retina of the various biochemical, histological and immunohistochemical effects were investigated. SpragueDawley rats were subjected to traumatic brain injury with a weight-drop device using 300 g-1 m weightheight impact. Twenty one rats were divided into three groups, as group 1 (vehicle-treated control), group 2 (vehicle-treated trauma) group 3 trauma + Potentilla fulgens ( P. Fulgens) 400 mg/kg/day, i.p.). Distilled water was used as vehicle. All rats were decapitated 5 days after the induction of trauma, and the protective effects of P. Fulgens were evaluated by histological, immunohistochemical and biochemical analyses. Although further studies are necessary to evaluate the time-and dose-dependent neuroprotective effects of P. Fulgens. Depending on whether trauma inhibits apoptosis of photoreceptor cells, ganglion cells, it is thought that the the support against the degeneration of neural connections can be considered. This study indicates that P.Fulgens is potentially useful for the treatment of eye disorders induced by traumatic brain injury.
El trauma de cráneo es una de las principales causas de morbilidad y mortalidad. Como resultado de un traumatismo craneal, la retina puede sufrir diversos efectos bioquímicos, histológicos e inmunohistoquímicos. Veintiún ratas Sprague-Dawley fueron sometidas a lesión craneal traumática con un dispositivo, de caída de peso, usando un impacto de 300 g-1 m de peso-altura. Las ratas fueron divididas en tres grupos: grupo 1 (control), grupo 2 (traumatismo) y grupo 3 trauma + Potentilla fulgens (400 mg / kg / día, i. p.). Se usó agua destilada como vehículo en todos los grupos. Las ratas fueron decapitadas 5 días después de la inducción del trauma, y se evaluaron los efectos protectores de P. Fulgens mediante análisis histológicos, inmunohistoquímicos y bioquímicos. Es necesario realizar más estudios para evaluar los efectos neuroprotectores, dependientes del tiempo y la dosis, de P. Fulgens. Dependiendo si el trauma inhibe la apoptosis de las células fotorreceptoras, se estima que la disposición de las células ganglionares ayuda contra la degeneración de las conexiones neuronales. P. Fulgens ha demostrado ser efectivo para el tratamiento de los trastornos oculares inducidos por lesión cerebral traumática.
Subject(s)
Animals , Rats , Craniocerebral Trauma/complications , Eye Injuries/drug therapy , Plant Extracts/administration & dosage , Potentilla/chemistry , Retina/pathology , Eye Injuries/etiology , Rats, Sprague-Dawley , Retina/drug effectsABSTRACT
In this study, the effectiveness of topical diclofenac sodium has been investigated in the treatment of microhyphema. A total of 62 patients with traumatic microhyphema were enrolled in a prospective, randomized, double-masked, placebo-controlled clinical study. Of these, 32 were given diclofenac eye drops, while 30 received a placebo. All were observed daily until there was complete recovery. One drop of diclofenac sodium or a placebo was applied four times a day. The efficacy evaluation was based on the measurement of visual acuity, slit-lamp assessment of anterior chamber cells and flare and duration of treatment. Diclofenac sodium was statistically favored over the placebo in flare and cell score. The duration of treatment of the diclofenac group was significantly shorter than the placebo group. Visual acuity of diclofenac sodium recipients was significantly better than the placebo recipients from the third to the sixth day of treatment. No statistical difference in final visual acuity was found between the two groups [P>0.05]. The research indicated that diclofenac sodium reduces microhyphema effectively and more quickly than the placebo, leading to early rehabilitation of patients following ocular contusion