RESUMEN
Oxaliplatin (OXL) is a chemotherapeutic drug used for metastatic and other types of cancer, but it causes peripheral neuropathy as a dose-limiting side effect. Herein, we used the rat model of OXL-induced peripheral neuropathy to demonstrate the protective effects of naringin (NRG) in this neuropathy. In this study, rats were injected with OXL (4 mg/kg, body weight, i.p.) in 5% glucose solution 30 min after oral administration of NRG (50 and 100 mg/kg, body weight) on the 1st, 2nd, 5th, and 6th days. OXL caused sensory and motor neuropathy (as revealed by the hot plate, tail flick, rota-rod, and cold hyperalgesia tests) in the sciatic nerve of rats. Coadministration of oral NRG alleviated OXL-induced sensory and motor neuropathy. Levels of superoxide dismutase, catalase, glutathione peroxidase, nuclear factor erythroid 2-related factor 2, Heme oxygenase-1, nuclear factor-κ B, tumor necrosis factor-α, interleukin-1ß, Bax, Bcl-2, caspase-3, paraoxonase, mitogen-activated protein kinase 14, neuronal nitric oxide synthase (nNOS), acetylcholinesterase, and arginase 2 in the sciatic nerve tissues were assessed by real-time polymerase chain reaction. Moreover, the protein levels of caspase-3, Bax, Bcl-2, intercellular adhesion molecules-1, glial fibrillary acidic protein, and nNOS were examined by Western blot analysis. NRG treatment significantly improved all the above-mentioned parameters and reduced OXL-induced oxidative stress, inflammation, and apoptosis in the sciatic nerve tissue. In conclusion, this study demonstrated that NRG significantly attenuated OXL-induced peripheral neuropathy and might be considered as a new protective agent to prevent the OXL-induced peripheral neuropathy.
Asunto(s)
Proteína Quinasa 14 Activada por Mitógenos , Enfermedades del Sistema Nervioso Periférico , Acetilcolinesterasa , Animales , Arginasa/efectos adversos , Arildialquilfosfatasa , Peso Corporal , Caspasa 3 , Catalasa/metabolismo , Moléculas de Adhesión Celular , Flavanonas , Proteína Ácida Fibrilar de la Glía , Glucosa/efectos adversos , Glutatión Peroxidasa , Hemo-Oxigenasa 1 , Interleucina-1beta , Óxido Nítrico Sintasa de Tipo I/efectos adversos , Oxaliplatino/efectos adversos , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/prevención & control , Sustancias Protectoras , Ratas , Superóxido Dismutasa , Factor de Necrosis Tumoral alfa/metabolismo , Proteína X Asociada a bcl-2RESUMEN
A single intraperitoneal injection of a gram-positive pathogen Clostridium perfringens (Cp) causes a remarkable down-regulation the constitutive nitric oxide synthase (cNOS) with a simultaneous increase in the activity of inducible NOS (iNOS) and the level of reactive nitrogen species in the rat brain major regions (cortex, striatum, hippocampus and hypothalamus) at 48 h post-administration of Cp. Treatment by both a semiconductor laser (SCL) and/or a light-emitting diode (LED) with same wavelength, energy density and time exposure (continuous wave, λ=654 nm, fluence=1.27 J/cm(2), time exposure=600 s) could modulate brain nitrergic response following Cp-infection. Besides, unlike the LED, the SCL-irradiation prevents the cNOS inhibition in all the studied brain regions and might be useful in restoring its function in neurotransmission and cerebral blood flow, along with providing a protective effect against nitrosative stress-induced iNOS-mediated injury in the brain regions.
Asunto(s)
Infecciones por Clostridium/radioterapia , Clostridium perfringens/efectos de la radiación , Hipotálamo/efectos de la radiación , Láseres de Semiconductores/uso terapéutico , Neuronas Nitrérgicas/efectos de la radiación , Animales , Infecciones por Clostridium/enzimología , Hipotálamo/enzimología , Hipotálamo/microbiología , Masculino , Neuronas Nitrérgicas/metabolismo , Óxido Nítrico Sintasa de Tipo I/efectos adversos , Óxido Nítrico Sintasa de Tipo I/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Distribución Aleatoria , Ratas , Especies de Nitrógeno Reactivo/biosíntesis , Especies de Nitrógeno Reactivo/efectos de la radiación , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the role of neuronal nitric oxide synthase (NOS1) in murine polymicrobial peritonitis and sepsis. DESIGN: Randomized experimental trial. SETTING: Animal research facility. SUBJECTS: B6129S NOS1+/+ and B6;129S4 NOS-/- mice. INTERVENTIONS: NOS1+/+ and NOS1-/- animals underwent cecal ligation and puncture (CLP) or sham surgery and received the NOS1 inhibitor 7-nitroindazole (7-NI) or vehicle. MEASUREMENTS AND MAIN RESULTS: After CLP, genetic deficiency and pharmacologic inhibition of NOS1 significantly increased risk of mortality [8.69 (3.27, 23.1), p<0.0001 and 1.71 (1.00, 2.92) p=0.05, hazard ratio of death (95% confidence interval) for NOS1-/- and 7-NI-treated NOS1+/+ respectively] compared with NOS1+/+ animals. In 7-NI-treated NOS1+/+ animals, there were increases (6 h) and then decreases (24 h), whereas in NOS-/- animals persistent increases in blood bacteria counts (p=0.04 for differing effects of 7-NI and NOS1-/-) were seen compared with NOS1(+/+) animals. After CLP, NOS1(-/-) had upregulation of inducible NOS and proinflammatory cytokines and greater increases in serum tumor necrosis factor-alpha and interleukin-6 levels compared with NOS1+/+ mice (all p<0.05). Following CLP, there were similar significant decreases in circulating leukocytes and lung lavage cells (pAsunto(s)
Óxido Nítrico Sintasa de Tipo I/deficiencia
, Peritonitis/fisiopatología
, Sepsis/fisiopatología
, Animales
, Femenino
, Expresión Génica
, Ratones
, Óxido Nítrico Sintasa de Tipo I/efectos adversos
, Óxido Nítrico Sintasa de Tipo I/análisis
, Óxido Nítrico Sintasa de Tipo I/genética
, Óxido Nítrico Sintasa de Tipo I/metabolismo
, Óxido Nítrico Sintasa de Tipo I/farmacología
, Peritonitis/mortalidad
, Distribución Aleatoria
, Medición de Riesgo
, Sepsis/mortalidad
, Análisis de Supervivencia
, Estados Unidos