ABSTRACT
Objective:To observe the effects of Fushengong prescription on p38 mitogen-activated protein kinase（p38 MAPK） signal pathway of rats with chronic renal failure（CRF），and to explore its mechanism of reducing inflammatory reaction of renal tissues and delaying the progress of renal interstitial fibrosis. Method:The 55 male Sprague-Dawley rats were randomly divided into normal group，model group， and low，medium and high dose groups of Fushengong prescription，with 11 rats in each group.The normal group was routinely reared， and the other four groups of rats were fed a diet containing 0.5% adenine to produce a model of CRF， which was continuously molded for 21 days.After successful modeling，all rats switched to conventional feed.Normal group and model group were given normal saline 20 mL·kg-1，and each group of Fushengong prescription was given 4，8，16 g·kg-1 of water prescription once a day for 30 days.After the experiment，Masson staining was used to observe the degree of renal interstitial fibrosis.The expression of monocyte chemotactic protein-1（MCP-1） in renal tissues was detected by immunohistochemistry. The expression of phosphorylated p38 mitogen-activated protein kinase（p-p38 MAPK） and transformed growth factor-β1（TGF-β1） in renal tissues were detected by Western blot. Result:Compared with normal group，the renal interstitial collagen deposition increased significantly，the average optical density value of MCP-1 and the expression levels of p-p38 MAPK and TGF-β1 also increased significantly in model group （P<0.05）. Compared with model group，the renal interstitial collagen deposition reduced significantly，the average optical density value of MCP-1 and the protein expression levels of p-p38 MAPK and TGF-β1 also decreased significantly in each dose group of Fushengong prescription（P<0.05）. Conclusion:Fushengong prescription can effectively inhibit the expression of related inflammatory factors in the renal tissue of CRF rats，so as to reduce the inflammatory response in the renal tissue and delay the progress of renal interstitial fibrosis，the mechanism of which may be related to inhibit the activation of p38 MAPK signal transduction pathway.
ABSTRACT
SUMMARY: Titanium dioxide nanoparticles (TiO2 NPs) are widely used in many commercial products, nanomedicine, agriculture, personal care products, different industries and pharmaceutical preparations with potential risk in human health and the environment. The current work was conducted to investigate the renal damage that might be induced by the acute toxicity TiO2 NPs. A total of 40 healthy male adult Wistar albino rats (Rattus norvegicus) were exposed to TiO2 NPs (126, 252, 378 mg/kg bw) for 24 and 48 h. Fresh portions of the kidneys from each rat were processed for histological and histochemical alterations. In comparison with respective control rats, exposure to TiO2 NPs has marked the following glomerular, tubular and interstitial alterations including the followings: glomerular congestion, Bowman's capsule swelling and dilatation, inflamed glomeruli, renal tubules cloudy swelling, karyorrhexis, karyolysis, infiltration of inflammatory cells, congestion, necrosis, hydropic degeneration, dilatation and congestion of blood vessels, hyaline droplets and hyaline casts precipitation, interstitial edema and fibrosis. From the findings of the current work one may conclude that TiO2 NPs are capable of inducing kidney damage with more insulation in the cortex and the proximal convoluted tubules than the medulla and the distal ones respectively. In addition, it might be concluded that renal damage induced by these nanomaterials is dose and duration of exposure dependent. Further hematological, biochemical, immunohistochemical, and ultra-structural studies are recommended.
RESUMEN: Las nanopartículas de dióxido de titanio (TiO2 NP) se usan ampliamente en muchos productos comerciales, nanomedicina, agricultura, productos para el cuidado personal, diferentes industrias y preparaciones farmacéuticas con riesgo potencial para la salud humana y el medio ambiente. El trabajo actual se realizó para investigar el daño renal que podría ser inducido por la toxicidad aguda NP de TiO2. Un total de 40 ratas Wistar albinas adultas sanas (Rattus norvegicus) fueron expuestas a TiO2 NP (126, 252, 378 mg / kg de peso corporal) durante 24 y 48 h. Las muestras de los riñones de las ratas se procesaron para estudios histológicos e histoquímicos. En comparación con las ratas control, la exposición de las ratas a TiO2 NP presentaron las siguientes alteraciones glomerulares, tubulares e intersticiales: congestión glomerular, dilatación de la cápsula de Bowman, inflamación glomerular, túbulos renales aumentados, cariorrexis, cariólisis, infiltración de células inflamatorias, congestión, necrosis, degeneración hidrópica, dilatación y congestión de vasos sanguíneos, gotas y precipitaciones hialina, edema intersticial y fibrosis. A partir de los hallazgos del trabajo actual, se puede concluir que las NP de TiO 2 son capaces de inducir daño renal con más aislamiento en la corteza y en los túbulos contorneados proximales que en la médula y los túbulos contorneados distales, respectivamente. Además, se podría concluir que el daño renal inducido por estos nanomateriales depende de la dosis y la duración de la exposición. Se recomiendan estudios adicionales hematológicos, bioquímicos, inmunohistoquímicos y ultraestructurales.