RESUMO
The aim of this study was to investigate the effects of vitamin C on cisplatin (DDP)-induced anemia and explore its possible mechanisms in rats. Adult male Sprague-Dawley rats were randomly divided into six groups: control, vitamin C 50, vitamin C 100, DDP, DDP plus vitamin C 50 and DDP plus vitamin C 100-treated groups. DDP was intravenous injected as a single dose and vitamin C was administered by gavage. Serum erythropoietin (Epo), hemoglobin (Hb) and blood urea nitrogen (BUN) concentration were measured 4 and 14 days after DDP treatment. The changes of renal tissue were examined by light microscope. Administration of DDP to rats induced anemia and nephrotoxicity, characterized with a significant decrease in serum Epo and Hb and increase in BUN concentrations. Pathological examination revealed that DDP caused significant renal damage in rats. Vitamin C administration produced amelioration in biochemical indices of anemia and nephrotoxicity and in histological change when compared to group DDP alone; concurrent administration of vitamin C at doses of 100 mg/kg being more effective. Results from this study indicate that the novel natural antioxidant vitamin C might have protective effect against DDP-induced anemia in rats.
Assuntos
Anemia/prevenção & controle , Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Cisplatino/efeitos adversos , Anemia/sangue , Anemia/induzido quimicamente , Animais , Antioxidantes/administração & dosagem , Ácido Ascórbico/administração & dosagem , Relação Dose-Resposta a Droga , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Cerebral ischemiareperfusion injury (CIRI), caused by the reperfusion of blocked vessels following ischemic stroke, can lead to secondary brain injury. Throughout CIRI, apoptosis serves an important role. Astragaloside IV is a potential neuroprotectant that alleviates CIRI by inhibiting apoptosis. The calciumsensing receptor (CaSR) is a Gproteincoupled receptor, the activation of which aggravates ischemiareperfusion injury. The aim of the present study was to investigate whether the protective effect of Astragaloside IV on CIRI may be associated with the regulation of CaSR. A rat middle cerebral artery occlusion/reperfusion (MCAO/R) model and an oxygen and glucose deprivation/reoxygenation (OGD/R) model of pheochromocytoma (PC12) cells were used to study the neuronal injury induced by CIRI. Neurological function scores (NFS), 2,3,5triphenylterazolium chloride and hematoxylin and eosin staining were used to determine brain damage in rats. Cell viability was measured to evaluate the injury of OGD/R PC12 cells. Western blotting was used to examine the expression of proteins associated with apoptosis and CaSR. The CaSR antagonist NPS2143 and agonist GdCl3 were used to further confirm the effects of CaSR during the process of apoptosis. The results demonstrated that Astragaloside IV alleviated CIRI by decreasing the NFS of rats, reducing the infarction volume of the brain and promoting the viability of PC12 cells, as well as inhibiting the expression of cleaved caspase3 and CaSR, which was induced by CIRI. The results of the present study suggested that the activation of CaSR may be involved in CIRIinduced brain damage in rats, and that Astragaloside IV may alleviate CIRI by inhibiting CaSR activationinduced apoptosis.
Assuntos
Apoptose/efeitos dos fármacos , Transtornos Cerebrovasculares/metabolismo , Receptores de Detecção de Cálcio/antagonistas & inibidores , Traumatismo por Reperfusão/metabolismo , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/patologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Receptores de Detecção de Cálcio/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologiaRESUMO
Oxidative stress has been proven to be involved in cisplatin (DDP)-induced toxicity. The aim of the present study was to investigate a possible protective role of grape seed proanthocyanidin extract (GSPE) in DDP-induced spermiotoxicity. GSPE at 200 mg kg(-1) d(-1) and 400 mg kg(-1) d(-1) was orally administered for 15 consecutive days, starting 10 days before a single intraperitoneal dose of DDP (7 mg kg(-1)). Results revealed that testicular and epididymal weight, epididymal sperm count, motility and morphology, the activities of GSH-Px and SOD, and GSH levels were significantly decreased whereas the level of MDA was significantly increased in the DDP group rats. GSPE treatment significantly attenuated the harmful effects of DDP-induced lipid peroxidation, oxidative stress, loss of genital organ weight, as well as function of reproductive organs. These changes were restored to near normal levels by GSPE at 400 mg kg(-1) d(-1). In conclusion, GSPE has dose dependent protective effects against DDP-induced rat testicular toxicity.