Pectin/chitosan/tripolyphosphate encapsulation protects the rat lung from fibrosis and apoptosis induced by paraquat inhalation.

BACKGROUND: Paraquat poisoning leads to lung injury and pulmonary fibrosis. The effect of paraquat encapsulation by previously described Pectin/Chitosan/Tripolyphosphate nanoparticles on its pulmonary toxicity was investigated in present study in a rat model of poison inhalation. MATERIAL AND METHOD: The rats inhaled nebulized different formulation of paraquat (n = 5) for 30 min in various experimental groups. Lung injury and fibrosis scores, Lung tissue enzymatic activities, apoptosis markers were determined compared among groups. RESULTS: Encapsulation of paraquat significantly rescued both lung injury and fibrosis scores. Lung MDA level was reduced by encapsulation. Paraquat poisoning led to lung tissue apoptosis as was evidenced by higher Caspase-3 and Bax/Bcl2 expressions in rats subjected to paraquat inhalation instead of normal saline or free nanoparticles. Again, nanoencapsulation reduced these apoptosis markers significantly. Alpha-SMA expression was also reduced by encapsulation. Nanoparticles per se have no or little toxicity as was evidenced by inflammatory and apoptotic markers and histological scores. CONCLUSION: In a rat model of inhalation toxicity of paraquat, loading of this herbicide on PEC/CS/TPP nanoparticles reduced acute lung injury and fibrosis. The encapsulation also led to lower apoptosis, oxidative stress and alpha-SMA expression in the lung tissue.

Ginkgo biloba attenuated hepatotoxicity induced by combined exposure to cadmium and fluoride via modulating the redox imbalance, Bax/Bcl-2 and NF-kB signaling pathways in male rats.

Aim of this study was to investigate the efficacy of Ginkgo Biloba (G.B) hydro-ethanolic extract against hepatotoxicity induced by combined exposure to cadmium (Cd) and fluoride (F) in Wistar rats. Animals were exposed to F (30 mg/L) + Cd (40 mg/L), F + Cd plus G.B (50,100 and 200 mg/kg), G.B (200 mg/kg), F + Cd plus Vit C(1000 mg/L) in drinking water for 42 days. Significant raise in liver enzymes and histopathological changes were observed in F + Cd treated rats. F + Cd exposure enhanced protein and glutathione oxidation, lipid peroxidation and decreased superoxide dismutase activity. F and Cd combination also caused mitochondrial dysfunction, swelling and mitochondrial membrane potential collapse in liver isolated mitochondria. Up-regulation of inflammatory genes (TNF-α, IL-1ß and NF-kB) and pro-apoptotic Bax as well as down-regulation of anti-apoptotic Bcl-2 were detected after co-exposure to F and Cd. Interestingly, G.B alleviated F + Cd induced liver oxidative stress, mitochondrial damage and prevented inflammation and apoptosis. Furthermore, decrease in serum liver enzymes and improvement of histopathologic lesions were observed in G.B treated rats. This study explored the potential beneficial role of G.B on F + Cd combined hepatotoxic effects via considering its possible antioxidant, anti-inflammatory, mitochondrial protection and anti-apoptotic effects.

Pectin/Chitosan/Tripolyphosphate Nanoparticles: Efficient Carriers for Reducing Soil Sorption, Cytotoxicity, and Mutagenicity of Paraquat and Enhancing Its Herbicide Activity.

As a potent herbicide capable of contaminating water and soil environments, paraquat, which is still widely used worldwide, is toxic to mammals, algae, aquatic animals, etc. Paraquat was loaded on novel nanoparticles composed of pectin, chitosan, and sodium tripolyphosphate (PEC/CS/TPP). The size, polydispersity index, and ζ potential of nanoparticles were characterized. Further assessments were carried out by SEM, AFM, FT-IR, and DSC. The encapsulation was highly efficient, and there was a delayed release pattern of paraquat. The encapsulated herbicide was less toxic to alveolar and mouth cell lines. Moreover, the mutagenicity of the formulation was significantly lower than those of pure or commercial forms of paraquat in a Salmonella typhimurium strain model. The soil sorption of paraquat and the deep soil penetration of the nanoparticle-associated herbicide were also decreased. The herbicidal activity of paraquat for maize or mustard was not only preserved but also enhanced after encapsulation. It was concluded that paraquat encapsulation with PEC/CS/TPP nanoparticles is highly efficient and the formulation has significant herbicide activity. It is less toxic to human environment and cells, as was evidenced by less soil sorption, cytotoxicity, and mutagenicity. Hence, paraquat-loaded PEC/CS/TPP nanoparticles have potential advantages for future use in agriculture.

Immunomodulatory effects of bee venom in human synovial fibroblast cell line.

As in Iranian traditional medicine, bee venom (BV) is a promising treatment for the rheumatoid arthritis (RA) which is considered as a problematic human chronic inflammatory disease in the present time. Smoking is considered to be a major risk factor in RA onset and severity. The main aim of this study is to investigate the effects of BV on cigarette smoke-induced inflammatory response in fibroblast-like synoviocytes (FLS). Cytotoxicity of cigarette smoke condensate (CSC) and bee venom were determined by the tetrazolium (MTT) method in cultured synovial fibroblastes. The expression of interleukin-1ß and sirtuin1 mRNA were analyzed by SYBR green real-time quantitative PCR. Differences between the mean values of treated and untreated groups were assessed by student t-test. Based on MTT assay, CSC and BV did not exert any significant cytotoxic effects up to 40 µg/mL and 10 µg/mL, respectively. Our results showed that interleukin-1ß mRNA level was significantly up-regulated by CSC treatments in LPS-stimulated synoviocytes in a dose-dependent manner. Conversely, the expressions of IL-1ß and Sirt1 were up-regulated even in lower concentrations of BV and attenuated at higher concentrations. Also, BV attenuated the CSC-induced and LPS-induced inflammatory responses in synovial fibroblasts. Our results support the epidemiological studies indicating pro-inflammatory effects of CSC and anti-inflammatory effects of BV on FLS cell line.