| Summary: | 碩士 === 南臺科技大學 === 生物科技系 === 104 === Paraquat (PQ) is a widely used herbicide in the world but highly toxic to both humans and animals. After ingestion, PQ is rapidly absorbed into the bloodstream and concentrates primarily in pulmonary tissue, and then develops into irreversible pulmonary fibrosis, which is the primary cause of death. Pulmonary fibrosis is characterized by fibroblast proliferation, myofibroblast differentiation, and deposition of extra-cellular matrix in the lung parenchyma. Carbon monoxide (CO) is toxic to humans and animals, recent studies suggest low dose, 10 to 500 ppm, CO has anti-inflammatory effects, and protection against hypoxic as well as ischemic lung injury. Studies revealed Carbon monoxide releasing molecules (CORMs) can improve viability of paraquat-treated cardiomyocytes and decrease pulmonary fibrosis induced by bleomycin. These findings suggest CORMs may have therapeutic effect on paraquat-induced pulmonary fibrosis.
This study showed first in vitro CORMs (CORM-3 or CORM-A1) has dose related anti-oxidant effects (free radicals, ABTS+•, DPPH•, scavengers). In vitro cell study, 20 μM CORM-3 can improve cell injury of RAW264.7/A549/MRC-5 cell after paraquat/H2O2-treatment 24 hours (increase survival rate of cells).Pretreatment with 20-100 μM CORMs (CORM-3 or CORM-A1) can decrease high level of CTGF and ANGII which released by paraquat-treated A549/MCR-5. In vivo animal study showed intraperitoneal injection of CORMs improve the survival for 14 days of mice fed with paraquat, and decrease overexpression of collagen fiber (PAS and Masson stain) and TGF-β (IHC stain). By western blot analysis, 10 mg/kg CORMs (CORM-3 or CORM-A1) decrease protein expression of COX-2, α-SMA and TNF- increased by paraquat. We also found prescription with 5 mg/kg CORMs (CORM-3 or CORM-A1) decrease serum level of Hydroxyproline of mice fed with paraquat. Overall, this study indicates that CORMs would be an attractive therapeutic approach to attenuate the progression of pulmonary fibrosis induced by paraquat.
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