The Protective Effects of Nebulized Nano-Curcumin Against Bleomycin-Induced Pulmonary Fibrosis in Rats

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease affecting the lung, and currently there is no efficient therapy for this condition. Curcumin, as a natural anti-inflammatory and antioxidant agent, could repress the pulmonary fibrosis (PF) caused by Bleomycin (BLM). Objectives: The aim of the research was to evaluate the protective activity of a nano-formulation of curcumin administered by inhalation on BLM-induced PF in rats. Methods: Eighty rats were randomly divided into eight experimental groups. Group one (control) that received saline intratracheally (IT) and subjected to vehicle inhalation. Group two to eight each received a single dose of BLM (5 IU/kg, IT) along with vehicle inhalation, oral prednisolone, oral curcumin, curcumin inhalation, and nano-curcumin inhalation with the doses of 50, 100, and 200 µg/kg, respectively. In the control and other groups, BLM was injected intratracheally on the first day of the experiment. In the treatment groups, curcumin suspension was prepared in distilled water and applied through nebulization for 21 consecutive days after BLM intratracheal administration. Then the rats were euthanized, and inflammatory cytokines (TNF-α, TGF-β, PDGF), hydroxyproline, and IL-10 (as a protective cytokine) were measured. Also, lung histopathological features were examined. Results: The synthesized nano-formulation reduced the overall hydroxyproline content of lungs in BLM-treated rats (P < 0.002). In addition, TNF-α, TGF-β, and PDGF levels significantly increased in the lungs of BLM-instilled rats (P < 0.001). However, the nano-formulation of curcumin (200 µg/kg) significantly decreased the levels of these inflammatory cytokines (P < 0.001) and increased IL-10 level (P = 0.0144) compared with the control group. Conclusions: The nebulization of nano-curcumin is suggested as a novel approach for the treatment of PF induced by BLM in rats. Our findings revealed that the inhalation (as a safe local drug delivery system approach) of the nano-curcumin at a dose of 200 µg/kg (formulated by cyclodextrin) could effectively protect the lung against PF.