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

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.

Maprotiline ameliorates isoflurane-induced microglial activation via regulating triggering receptor expressed in myeloid cells 2 (TREM2).

Isoflurane-induced neurotoxicity has attracted much interest. Recent studies suggest that isoflurane causes microglial activation, resulting in an inflammatory response and microglial insult. Maprotiline is a novel drug that has been licensed as an antidepressant with considerable anti-inflammatory activity. However, it is still unknown whether maprotiline possesses a protective effect against isoflurane-induced microglial insult. Here, we found that maprotiline ameliorated isoflurane-caused reduction in BV2 microglial cell viability and lactate dehydrogenase (LDH) release. Maprotiline mitigated isoflurane-induced oxidative stress by inhibiting reactive oxygen species (ROS) production and increasing superoxide dismutase (SOD) activity. Isoflurane-induced expression and production of inflammatory markers including tumor necrosis factor (TNF-α), interleukin (IL)-1ß, cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) were decreased in maprotiline-treated cells. Maprotiline inhibited the mRNA and protein levels of Iba1, a marker of microglial activation, in isoflurane-induced BV2 cells. Maprotiline treatment restored isoflurane-induced reduction of TREM2 in BV2 microglial cells. In addition, the knockdown of TREM2 abolished the beneficial effects of maprotiline against isoflurane. Collectively, maprotiline exerted protective effects against isoflurane-caused oxidative stress, inflammatory response, and cell injury via regulating TREM2. These findings show that maprotiline prevented the isoflurane-induced microglial activation, indicating that maprotiline might be used as an optimal therapeutic agent for preventing the isoflurane-caused neurotoxicity.