Intranasal Curcumin ameliorates Silica induced Inflammation and Pulmonary Fibrosis via NRF-2/Keap-1 pathway and autophagy in mice model

Silicosis, one of the most serious lung fibrotic illnesses in the world is due to repeated silica dust exposures. Aberrant tissue repair and persistent inflammation in silicosis is due to occupational exposures to silica particles but specific molecular mechanism has not yet been identified. Present study was undertaken to investigate impact of silica exposures leading to lung damage and fibrosis and plausible therapeutic interventions. Here, mice model of silicosis was established where silica induced oxidative lung damage and fibrotic response has been thoroughly explored and an anti-inflammatory molecule, curcumin, derived from Curcuma longa has been for discovered for its anti-oxidant potential. In present study, curcumin was administered every alternate day for 35 days an hour prior to silica exposure and molecular mechanism of anti-inflammatory and anti-oxidative potential of curcumin was examined. Silica induced reactive oxygen species (ROS) were repressed by curcumin thereby autophagy was stimulated and deposition of damaged mitochondria were suppressed. Reduced oxidative stress resulted in reduced number of inflammatory cells, mainly neutrophils and macrophages. Curcumin treatment has reduced inflammation and the aberrant collagen repair which followed its protective benefits in mice. Curcumin also inhibited oxidants by boosting antioxidant enzyme activities by triggering Nrf2-Keap1 pathway. Autophagy markers like, PINK1, PARKIN, Cyt-c, P62/SQSTM levels were elevated in silicosis group which were significantly lowered after curcumin and dexamethasone treatment. Higher numbers of damaged mitochondria after silica inhalations were also reduced in curcumin administered groups. Curcumin initiated autophagy resulted in reduced silica-induced mitochondria-dependent apoptosis which may suggest molecular mechanism based therapeutic implications for silicosis.