Curcumin relieves paraquat‑induced lung injury through inhibiting the thioredoxin interacting protein/NLR pyrin domain containing 3‑mediated inflammatory pathway

Abstract

When paraquat (PQ) enters the human body, it increases oxidative stress and inflammation, ultimately resulting in acute lung injury (ali). curcumin, a naturally occurring compound, has been reported to ameliorate PQ-induced ali; however, the underlying molecular mechanisms remain unclear. in the present study, normal lung fibroblasts (WI-38VA13) were treated with 10 µmol/l PQ for 48 h, followed by a further 48 h incubation with 300 µmol/l curcumin. cells were then harvested to determine their viability. Flow cytometry was performed to analyze the levels of reactive oxygen species (roS) and the rate of apoptosis. The levels of apoptotic proteins and activation of the thioredoxin interacting protein/NLR pyrin domain containing 3 (TXNIP/NLRP3) axis were measured via reverse transcription-quantitative polymerase chain reaction and western blot analyses. Proinflammatory cytokine levels were examined using enzyme-linked immunosorbent assays. Finally, the expression levels of notch1, extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated-ERK1/2 were evaluated via western blotting. Following treatment with curcumin, PQ-induced increases in roS levels and apoptosis were significantly attenuated, and Bcl-2 expression levels were upregulated, whereas those of Bax were downregulated. It was also observed that curcumin treatment downregulated the expression levels of TXniP, nlrP3, interleukin (il)-1β and IL-18, and downstream caspase-1 compared with PQ treatment alone. Curcumin significantly attenuated the upregulation of Notch1 without affecting ERK1/2 phosphorylation. The present findings suggested that the inhibitory effects of curcumin on TXINP1 may inhibit activation of the NLRP3 inflammasome, subsequently suppressing the upregulation of proinflammatory cytokines and ultimately improving PQ-induced ali.

The Inhibitory Effect of Curcumin on Virus-Induced Cytokine Storm and Its Potential Use in the Associated Severe Pneumonia

“…Curcumin is able to reverse this effect and enhance the effectiveness of SOD so as to maintain the oxidant/antioxidant balance and mitigate liver damage (Hemeida and Mohafez, 2008). Recently, curcumin was reported to oppose the effect of ROS on pro-inflammatory cytokine expression (e.g., IL-1b, IL-18) by downregulation of the thioredoxin interacting protein/NLR pyrin domain containing 3 (TXNIP/NLRP3) (Ren et al, 2019).…”

Aspirin Eugenol Ester Attenuates Paraquat-Induced Hepatotoxicity by Inhibiting Oxidative Stress

“…Some studies have shown that PQ-induced cytotoxicity is related to oxidative stress, including excessive production of ROS and lipid peroxidation (Matern et al, 2015;Ren et al, 2019;Schuttler et al, 2019). The main characteristics of oxidative stress are dysfunction of antioxidant system or excessive production of free radicals (El-Boghdady et al, 2017;Guo et al, 2017;Cavaliere et al, 2019;Lopes et al, 2019).…”

“…Currently, the molecular mechanism of hepatotoxicity induced by PQ is not completely understood. It is known that the redox response is one of the main factors involved in the toxic effects of PQ (Ren et al, 2019). It has been reported that PQ molecules can interfere with the electron transport chain and then inhibit the synthesis of NADPH (Gao et al, 2018).…”

Thioredoxin-Interacting Protein (TXNIP) with Focus on Brain and Neurodegenerative Diseases

“…These studies demonstrate that derivatized curcumin molecules were more effective than curcumin alone in lowering TXNIP expression. Other studies have shown the effectiveness of curcumin in vitro and in vivo in inhibiting TXNIP expression but at higher doses than we used for testing the fluorinated curcumin compound [ 163 , 164 ]. The effect of curcumin on TXNIP expression appears to be through the activation of AMPK [ 81 , 165 ].…”