Silver nanoparticles (AgNPs)embedded poly ( N-vinylpyrrolidone/dextran) hydrogels were prepared by gamma radiation. Highly stable and uniformly distributed AgNPs have been obtained within hydrogel networks as nanoreactors via in situ reduction of silver nitrate using sodium borohydride as reducing agent. The formation of AgNPs has been confirmed by Fourier transform infrared spectroscopy. The ultraviolet-visible spectroscopy measurements show a distinct characteristic absorption peaks around 420 nm, indicating the formation of AgNPs. X-ray diffraction analysis and dynamic light scattering demonstrated that the hydrogels have regulated the AgNPs size to a nanoscale. The combination of the AgNPs with doxorubicin (DOX) as a model of antitumor drug forms a new biocompatible nanodrug. Our results show that the AgNPs effectively increased survival rate and decreased tumor volume of Ehrlich ascites carcinoma-bearing mice more than the DOX-treated group and enhanced the cytotoxicity of DOX in different human cancer cell lines (HepG2, T47D, and PC3). DOX-AgNPs decreased malondialdehyde and total nitrate/nitrite levels and increased superoxide dismutase activity and glutathione content in the rat cardiac tissues compared with the DOX-treated group. In conclusion, DOX-AgNPs improved therapeutic index and reduced DOX-induced cardiotoxicity via preservation of cardiac markers, which represents a promising candidate for cancer treatment.
The efficacy of bleomycin (BLM) as an antineoplastic drug is limited to the development of dose and time‐dependent pulmonary fibrosis. This study was intended to investigate the effect of N‐acetylcysteine (NAC) on BLM‐induced pulmonary fibrosis in rats. Twenty rats were randomly divided to the following four groups: Group one served as control; group two received BLM (15 mg/kg, intraperitoneal (ip)) for five consecutive days; group three received NAC (200 mg/kg, ip) for five consecutive days; and group four received NAC 1 hour before BLM for 5 days. The expression of connective tissue growth factor (CTGF), platelet‐derived growth factor (PDGF), silent information regulator l (SIRT1), AMP‐activated protein kinase (AMPK) were determined by qRT‐PCR in lung tissues. The changes in transforming growth factor‐beta1 (TGF‐β1), tumour necrosis factor‐α (TNF‐α), interleukin‐β1 (IL‐β1) and nuclear factor kappa‐β (NF‐κβ) in serum were measured by ELISA. The tissue antioxidant status was determined biochemically. BLM administration caused pulmonary fibrosis as evidenced by increased levels of inflammatory mediators (TGF‐β1, TNF‐α, IL‐β1 and NF‐κβ) in serum (P < .05), elevated lipid peroxidation and nitric oxide and depleted endogenous antioxidants in lung tissue (P < .05). The expression levels of SIRT1 and AMPK were significantly decreased (P < .05), while the expression levels of CTGF and PDGF were increased significantly in the BLM group as compared to the control group (P < .05). These alterations were normalized by NAC intervention. NAC markedly attenuated the lung histopathological changes and reduced collagen deposition. These results suggest that NAC exerted an ameliorative effect against BLM‐induced oxidative damage and pulmonary fibrosis via SIRT1/ AMPK/ NF‐κβ pathways.
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