RESUMEN
Gentamicin in overdose can lead to tubular injury and kidney dysfunction. Some antioxidants can protect kidneys against nephrotoxicity. This study was undertaken to evaluate the protective effects of Pistacia atlantica (P. atlantica) leaf hydroethanolic extract against gentamicin-induced nephrotoxicity in rats. Forty rats were divided into five groups: the first group received a daily intraperitoneal (i.p.) injection of normal saline. The second group received gentamicin (120 mg/kg, i.p.). The third, fourth, and fifth groups were orally treated with 200, 400, and 800 mg/kg of P. atlantica leaf hydroethanolic extract, respectively, and they also received gentamicin (120 mg/kg, i.p.). After seven days, serum malondialdehyde (MDA), creatinine (Cr), urea, uric acid, lipids profile, protein carbonyl (PC), and tumor necrosis factor-α (TNF-α) were determined. Also, a piece of kidney was used to determine catalase (CAT) and superoxide dismutase (SOD) activities, vitamin C, the gene expression of TNF-α, and for subsequent histopathological studies. Treatment with P. atlantica leaf hydroethanolic extract resulted in a significant increase (p < 0.05) in CAT, SOD, vitamin C, and high-density lipoprotein cholesterol, and significantly decreased (p < 0.05) the levels of Cr, urea, uric acid, MDA, PC, triglyceride, total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, TNF-α protein, and the gene expression of TNF-α compared with the untreated group. Histopathological studies show that in lymphocyte infiltration, remarkable reduction was observed in P. atlantica leaf hydroethanolic extract-treated groups, compared with the untreated group. The present study suggests that P. atlantica leaf hydroethanolic extract has protective effects against gentamicin-induced nephrotoxicity.
Asunto(s)
Antiinflamatorios/farmacología , Enfermedades Renales/tratamiento farmacológico , Fitoterapia , Pistacia/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Sustancias Protectoras/farmacología , Animales , Antibacterianos/efectos adversos , Gentamicinas/efectos adversos , Riñón/efectos de los fármacos , Riñón/metabolismo , Enfermedades Renales/sangre , Enfermedades Renales/inducido químicamente , Pruebas de Función Renal , Masculino , Ratas , Ratas WistarRESUMEN
Prostate cancer (PC) is one of the most common cancers among men. Progression of prostate cancer is associated with an increase in cellular level of interleukin-6 (IL-6). Gallic acid (GA) is a polyhydroxy phenolic compound which can inhibit the growth of cancer cells. The aim of this study was to evaluate the effects of GA treatment on cell viability, proliferation, invasion, IL-6 gene expression, IL-6 secretion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins in human prostate cancer PC3 cells. PC3 cells viability after treatment with GA (0-120µM) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of IL-6 was investigated using real-time polymerase chain reaction. Cellular concentration of pSTAT3, pERK1/2, and pAKT signaling proteins were determined by Western blotting technic. PC3 cells invasion was assessed by invasion assay test. Treatment with GA caused a significant decrease in cell viability, proliferation, invasion, cellular levels of pSTAT3, pERK1/2, and pAKT signaling proteins after 48h in a dose-dependent manner. The level of IL-6 and its gene expression decreased significantly in PC3 cells treated with GA. Our results show that IL-6 down-regulation and decreased IL-6 protein level in PC3 cells by GA resulted in diminishing of pSTAT3, pERK1/2, and pAKT signaling proteins which lead to the reduction of the cell survival, proliferation, and invasion in PC3 cells. Therefore, it seems that GA can be considered an anticancer agent in the treatment of prostate cancer.
Asunto(s)
Antineoplásicos/farmacología , Movimiento Celular/efectos de los fármacos , Ácido Gálico/farmacología , Interleucina-6/metabolismo , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Interleucina-6/genética , Masculino , Invasividad Neoplásica , Fosforilación , Neoplasias de la Próstata/enzimología , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transducción de Señal/efectos de los fármacos , Factores de TiempoRESUMEN
INTRODUCTION: Gentamicin can lead to acute tubular injury and kidney dysfunction. This study aimed to evaluate the effect of Ferulago angulata on kidney function and other markers in rats with gentamicin-induced nephrotoxicity. MATERIALS AND METHODS: Forty-eight male Wistar rats were divided into the following groups: group 1, the controls; group 2, rats receiving gentamicin (120 mg/kg body weight per day, intraperitoneal) for 7 days without treatment; groups 3, 4 and 5, rats receiving gentamicin for 7 days and oral treatment with 200 mg/kg, 400 mg/kg, and 800 mg/kg body weight per day of Ferulago angulate extract, respectively. Measurements included serum levels of creatinine, urea, uric acid, lipids, ferric-reducing antioxidant power, and protein carbonyl; kidney and serum levels of malondialdehyde; and serum and renal levels of tumor necrosis factor-α. Histopathology of kidney tissue was examined as well as renal catalase, superoxide dismutase, and vitamin C. RESULTS: Compared to treatment with gentamicin only, treatment with Ferulago angulata resulted in a significantly higher high-density lipoprotein cholesterol, ferric-reducing antioxidant plasma, renal catalase, superoxide dismutase, and vitamin C levels. It was also associated with significantly lower serum levels of creatinine, urea, uric acid, malondialdehyde, protein carbonyl, tumor necrosis factor-α, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol. Ferulago angulate was linked with a lower renal gene expression of tumor necrosis factor-α. CONCLUSIONS: The present study suggests that Ferulago angulate extract has protective effects against nephrotoxicity due to gentamicin.