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

OBJECTIVE: 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 48 h) after PQ intoxication than previously reported (after 2 weeks) and we aimed to study the protective effects of intranasal curcumin as new therapeutic strategy in mouse model. METHODS: Mice (Park's strain) were divided into five experimental groups (I) control, received only saline (0.9 % NaCl) (II) PQ, mice intoxicated with PQ (50 mg/kg, i.p., single dose); (III) curcumin, treated with curcumin (5 mg/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 (1 mg/kg, i.p) before an hour of PQ intoxication. After 48 h of the PQ exposure, all mice were sacrificed and samples were analyzed. RESULTS: Pretreatment with intranasal curcumin (5 mg/kg) could modify the PQ-intoxication (50 mg/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. CONCLUSION: 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 48 h and intranasal curcumin may prove as new therapeutic strategy for PQ induced ALI and fibroproliferation.

Intranasal curcumin ameliorates lipopolysaccharide-induced acute lung injury in mice.

Lipopolysaccharide (LPS) is one of the most powerful proinflammatory factor and can induce acute pulmonary inflammation even lung injury after inhalation or systemic administration. LPS induces sepsis and multiple organ damage. Curcumin (diferuloylmethane), a major component of turmeric, exhibits protection against LPS-induced acute lung injury (ALI). We aimed to investigate effects of intranasal curcumin on LPS-induced ALI in mice where curcumin (10 mg/kg, intranasal (i.n.) was given an hour before LPS exposure. After 24 h of intranasal LPS instillation, a marked increase in neutrophil recruitment and myeloperoxidase (MPO) activity was noted which were significantly ameliorated in curcumin treatment group. Oxidative stress markers like nitric oxide (NO), malondialdehyde (MDA) level and evans blue capillary leakage assay also revealed suppression after curcumin treatment; interestingly, levels of anti-oxidative enzymes such as superoxide dismutase (SOD) and catalase were upregulated. Inflammatory cytokine, tumour necrosis factor alpha (TNF-α) level was significantly attenuated by curcumin. Hence, intranasal curcumin could be a novel therapeutic strategy for LPS-induced ALI by directly targeting the lungs and enhancing anti-oxidant levels.