Curcumin inhibits paraquat induced lung inflammation and fibrosis by extracellular matrix modifications in mouse model.

Abstract

Paraquat (PQ), a potent herbicide can cause severe toxicity. We report here that fibroproliferation phase of acute lung injury (ALI) is initiated much earlier (within 48h) after PQ intoxication than previously reported (after 2weeks) and we aimed to study the protective effects of intranasal curcumin as new therapeutic strategy in mouse model. Mice (Park's strain)were divided into five experimental groups (I) control, received only saline (0.9% NaCl) (II) PQ, mice intoxicated with PQ (50mg/kg, i.p., single dose); (III) curcumin, treated with curcumin (5mg/kg, i.n) an hour before PQ administration; (IV)Veh, DMSO (equal volume to curcumin) given an hour before PQ exposure; (V) DEXA, mice treated with dexamethasone (1mg/kg, i.p) before an hour of PQ intoxication. After 48h of the PQ exposure, all mice were sacrificed and samples were analyzed. Pretreatment with intranasal curcumin (5mg/kg) could modify the PQ-intoxication (50mg/kg, i.p) induced structural remodeling of lung parenchyma at an early phase of acute lung injury. Significant increase in inflammatory cell count, reactive oxygen species and hydroxyproline levels were decreased after curcumin pretreatment (all p<0.05). Histological examination and zymography results were also found consistent. Our results show that curcumin pretreatment decreased the expression of alpha smooth muscle actin (α-SMA), matrix metalloproteinases-9 (MMP-9) and changed the expression of tissue inhibitors of metalloproteinase (TIMP-1) after PQ intoxication. Single toxic dose of PQ has initiated fibroproliferation within 48h and intranasal curcumin may prove as new therapeutic strategy for PQ induced ALI and fibroproliferation.