RESUMO
Paraquat is a green liquid toxin that is used in agriculture and can induce multi-organ including lung injury. Various pharmacological effects of Crocus sativus (C. sativus) were indicated in previous studies. In this research, the effects of C. sativus extract and pioglitazone on inhaled paraquat-induced lung inflammation, oxidative stress, pathological changes, and tracheal responsiveness were studied in rats. Eight groups of rats (n = 7 in each) including control (Ctrl), untreated paraquat aerosol exposed group (54 mg/m3, 8 times in alternate days), paraquat treated groups with dexamethasone (0.03 mg/kg/day, Dexa) as positive control, two doses of C. sativus extract (20 and 80 mg/kg/day, CS-20 and CS-80), pioglitazone (5 and 10 mg/kg/day, Pio-5 and Pio-10), and the combination of CS-20 + Pio-5 were studied. Total and differential WBC, levels of oxidant and antioxidant biomarkers in the BALF, lung tissue cytokine levels, tracheal responsiveness (TR), and pathological changes were measured. The levels of IFN-γ, IL-10, SOD, CAT, thiol, and EC50 were reduced, but MDA level, total and differential WBC count in the BALF and lung pathological changes were increased in the paraquat group (all, p < 0.001). The levels of IFN-γ, IL-10, SOD, CAT, thiol and EC50 were increased but BALF MDA level, lung pathological changes, total and differential WBC counts were reduced in all treated groups. The effects of C. sativus high dose and combination groups on measured parameters were equal or even higher than dexamethasone (p < 0.05 to p < 0.001). The effects of the combination of CS-20 + Pio-5 on most variables were significantly higher than CS-20 and Pio-5 alone (p < 0.05 to p < 0.001). C. sativus treatment improved inhaled paraquat-induced lung injury similar to dexamethasone and showed a synergistic effect with pioglitazone, suggesting possible PPAR-γ receptor-mediated effects of the plant.
Assuntos
Lesão Pulmonar Aguda , Crocus , Pneumonia , Edema Pulmonar , Ratos , Animais , Paraquat/toxicidade , Paraquat/uso terapêutico , Crocus/metabolismo , Interleucina-10 , Pioglitazona/toxicidade , Pioglitazona/uso terapêutico , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/patologia , Pulmão , Edema Pulmonar/tratamento farmacológico , Estresse Oxidativo , Lesão Pulmonar Aguda/induzido quimicamente , Dexametasona/uso terapêutico , Superóxido Dismutase/metabolismo , Compostos de Sulfidrila/toxicidade , Compostos de Sulfidrila/uso terapêuticoRESUMO
The effect of Curcuma longa (Cl) ethanolic extract, nano-curcumin (Cu) and a PPARγ activator, pioglitazone on inhaled paraquat (PQ)-induced systemic inflammation and oxidative stress was examined in the present study. Control rats were exposed to normal saline and PQ groups to 27 and 54 mg/m3 (PQ-L and PQ-H) aerosols. Nine other PQ-H groups were treated with Curcuma longa (Cl, 150 and 600 mg/kg/day), nano-curcumin (Cu, 2 and 8 mg/kg/day), pioglitazone (Pio, 5 and 10 mg/kg), low dose of Pio + Cl and Cu and dexamethasone (0.03 mg/kg/day) for 16 days after PQ exposure period (n = 8). Total and differential WBC counts, malondialdehyde (MDA) and TNF-α levels were increased but thiol, catalase (CAT), superoxide dismutase (SOD), IL-10 and IFN-γ levels were decreased in the blood in the both PQ groups (p < 0.05 to p < 0.001). Treatment with Dexa and both doses of Cl, Cu, and Pio improved all measured variables compared to the PQ-H group (p < 0.05 to p < 0.001). The improvements of most variables in the treated group with low dose of Pio + Cl and Cu were higher than the effects of three agents alone. Systemic inflammation and oxidative stress induced by inhaled PQ were improved by Cl, Cu and Pio. In addition, a synergic effect between Pio with those of Cl and Cu was shown, suggesting PPARγ mediated effects of the plant and its derivative Cu.
Assuntos
Curcumina , Paraquat , Ratos , Animais , Paraquat/toxicidade , Paraquat/uso terapêutico , Curcumina/farmacologia , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , PPAR gama/metabolismo , PPAR gama/farmacologia , PPAR gama/uso terapêutico , Curcuma , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Hipoglicemiantes/farmacologiaRESUMO
In spite of the rapid emergence of numerous nanoparticles (NPs) for biomedical applications, it is often challenging to precisely control, or effectively tame, the bioactivity/toxicity of NPs, thereby exhibiting limited applications in biomedical areas. Herein, we report the construction of hyaluronic acid (HA)-laminated, otherwise toxic methylviologen (MV), NPs via ternary host-guest complexation among cucurbit[8]uril, trans-azobenzene-conjugated HA, and MV-functionalized polylactic acid NPs (MV-NPs). The high, nonspecific toxicity of MV-NPs was effectively shielded (turned off) by HA lamination, as demonstrated in cells, zebrafish, and mouse models. The supramolecular host-guest interaction-mediated HA coating offered several HA-MV-NP modalities, including hyaluronidase locally and photoirradiation remotely, to precisely remove HA lamination on demand, thereby endowing materials with the capability of selective decoating-induced activation (DIA) for applications as a user-friendly herbicide, a selective antibacterial agent, or an anticancer nanomedicine. This work offers facile supramolecular coating and DIA strategies to effectively tame and precisely control the bioactivity and toxicity of functional nanomaterials for diverse applications.
Assuntos
Antibacterianos/uso terapêutico , Antineoplásicos/uso terapêutico , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Paraquat/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Animais , Antibacterianos/química , Antibacterianos/toxicidade , Antineoplásicos/química , Antineoplásicos/toxicidade , Hidrocarbonetos Aromáticos com Pontes/química , Hidrocarbonetos Aromáticos com Pontes/toxicidade , Linhagem Celular Tumoral , Escherichia coli/efeitos dos fármacos , Feminino , Fluoretos/química , Fluoretos/efeitos da radiação , Gadolínio/química , Gadolínio/efeitos da radiação , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Imidazóis/química , Imidazóis/toxicidade , Raios Infravermelhos , Camundongos Endogâmicos C57BL , Testes de Sensibilidade Microbiana , Nanopartículas/química , Nanopartículas/efeitos da radiação , Nanopartículas/toxicidade , Paraquat/química , Paraquat/toxicidade , Poliésteres/química , Poliésteres/toxicidade , Staphylococcus aureus/efeitos dos fármacos , Túlio/química , Túlio/efeitos da radiação , Itérbio/química , Itérbio/efeitos da radiação , Peixe-ZebraRESUMO
Focal unilateral traumatic brain injury in the sensorimotor cortical region disturbed the functions of contralateral limbs controlled by the damaged hemisphere. A single intravenous injection of methylene blue (1 mg/kg) immediately before or 30 min after the injury significantly weakened functional disorders in the affected extremities. In vitro experiments showed that methylene blue effectively reduced death of cultured neurons provoked by paraquat or zinc ions producing the toxic effects on mitochondrias.
Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Azul de Metileno/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Células Cultivadas , Masculino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Paraquat/uso terapêutico , Ratos WistarRESUMO
Eosinophilia is not uncommon among returning travelers; however, the optimal diagnostic and therapeutic approach in travelers, as opposed to immigrants and refugees, is not clearly established. This was a retrospective case series. All returning travelers from developing countries presenting at the post-travel clinic with eosinophilia (>or= 500 cells/mcl) during 1994-2006 were evaluated. Data were compared with other referrals to the post-travel clinic and with a random sample of a pre-travel clinic. Of the 955 returning travelers evaluated during the study period, 82 (8.6%) had eosinophilia, and 44 (4.4%) were diagnosed with schistosomiasis. Another 38 (4.2%) cases presented with non-schistosomal eosinophilia (NSE), among whom a definite parasitologic diagnosis was achieved in only 23.7%. However, an empiric course of albendazole led to a clinical improvement in 90% of NSE cases. Helminthic disease probably accounts for the majority of cases of post-travel eosinophilia. Empiric albendazole therapy should be offered to undiagnosed NSE patients.