Ropivacaine has the potential to relieve PM2.5‑induced acute lung injury

Abstract

Ropivacaine is a commonly used local anesthetic in the clinic due to its low toxicity to the cardiovascular system or central nervous system, good tolerance and high clearance rate. The present study intended to investigate the effect of ropivacaine on PM2.5-induced acute lung injury (ALI) and reveal the underlying mechanism. After ropivacaine exposure, cell viability, oxidative stress and inflammation in PM2.5-induced BEAS-2B cells were assessed by Cell Counting Kit-8 and DCFH-DA staining, corresponding commercial kits and ELISA, respectively. The effects of ropivacaine on the expression of MMP9 and MMP12 and the proteins related to NLRP3/Caspase-1 signaling were then determined by western blot and reverse transcription-quantitative PCR analyses. In addition, NLR family pyrin domain containing 3 (NLRP3) agonist monosodium urate (MSU) was used to treat BEAS-2B cells followed by ropivacaine treatment and the effects on the above-mentioned cellular behaviors were determined again. The results indicated that the viability of BEAS-2B cells was decreased after PM2.5 induction, accompanied by aggravated oxidative stress and inflammation. However, ropivacaine alleviated oxidative stress and inflammation in PM2.5-induced BEAS-2B cells in a dose-dependent manner. Ropivacaine was also indicated to decrease the expression levels of NLRP3/Caspase-1 signaling-related proteins in PM2.5-induced BEAS-2B cells. Furthermore, cell viability was decreased, while oxidative stress and inflammatory response were aggravated, in PM2.5-induced BEAS-2B cells treated with MSU. In summary, the present results implied that ropivacaine exerted protective effects on PM2.5-induced ALI, and this effect may be related to NLRP3/Caspase-1 signaling.

Air-pollutant particulate matter 2.5 (PM2.5)-induced inflammation and oxidative stress in diseases: Possible therapeutic approaches

“…Hence, NOX1/4 may be a druggable target to reduce air pollutant PM2.5-induced endothelial dysfunction and associated cardiovascular diseases. The pharmacological effect of Ropivacaine, a widely used local anesthetic, on PM2.5-induced acute lung injury has been explored in cultured lung cells [72]. Exposure to PM2.5 (100µg/ml) induces the inflammatory and oxidative stress in lung cells BEAS-2B as shown by increased expression of inflammatory cytokines IL-6, IL-8, IL-1, TNF- and oxidative stress-related MDA, and decreased expression of GSH.…”

“…Exposure to PM2.5 (100µg/ml) induces the inflammatory and oxidative stress in lung cells BEAS-2B as shown by increased expression of inflammatory cytokines IL-6, IL-8, IL-1, TNF- and oxidative stress-related MDA, and decreased expression of GSH. However, pretreatment of BEAS-2B cells with Ropivacaine (1 µM, 10 µM, 100 µM) reduces PM2.5-induced inflammatory pathway, oxidative stress, and cell death through downregulation of inflammasome Nlrp3 and apoptotic caspase pathways [72], indicating Ropivacaine has potential to reduce PM2.5-induced inflammation, oxidative stress, and thus may be effective in diminishing lung injury-associated pathologies. Similarly, pretreatment of human bronchial epithelial cells (16HBE) with Caspase inhibitors Z-VAD-FMK and VX-765 block wood smoke-derived PM2.5 (5, 10, 20 µg/ml)-induced inflammation and pyroptosis of 16HBE cells as evidenced by decreased levels of LDH activity, caspase, inflammatory cytokines IL-1 and IL-18, the downstream targets of Nlrp3 [19].…”

Air-pollutant Particulate Matter 2.5 (PM2.5)-induced Inflammation and Oxidative Stress in Diseases: Possible Therapeutic Approaches

“…Exposure to PM2.5 (100µg/ml) induces the inflammatory and oxidative stress in lung cells BEAS-2B as shown by increased expression of inflammatory cytokines IL-6, IL-8, IL-1 , TNF-and oxidative stress-related MDA, and decreased expression of GSH. However, pretreatment of BEAS-2B cells with Ropivacaine (1 µM, 10 µM, 100 µM) reduces PM2.5-induced inflammatory pathway, oxidative stress, and cell death through downregulation of inflammasome Nlrp3 and apoptotic caspase pathways [72], indicating Ropivacaine has potential to reduce PM2.5-induced inflammation, oxidative stress, and thus may be effective in diminishing lung injury-associated pathologies. Similarly, pretreatment of human bronchial epithelial cells (16HBE) with Caspase inhibitors Z-VAD-FMK and VX-765 block wood smoke-derived PM2.5 (5,10.…”