Carvacrol protects the ARPE19 retinal pigment epithelial cells against high glucose-induced oxidative stress, apoptosis, and inflammation by suppressing the TRPM2 channel signaling pathways

Curcumin attenuates hydroxychloroquine-mediated apoptosis and oxidative stress via the inhibition of TRPM2 channel signalling pathways in a retinal pigment epithelium cell line

“…The accumulated data indicate that ARPE19 cell death is caused by the upregulation of apoptosis via increases in CAS/3, CAS/8, and CAS/9 activation [ 11 , 12 , 16 ]. After observing the protective roles of CRC and TRPM2 antagonist (CRV) on retina cell death in the ARPE19 cells, we suspected an increase in apoptosis and caspases in these cells.…”

“…The detrimental oxidative and apoptotic effects of medicines such as HCQ and chloroquine have been experimentally studied using ARPE19 cells as a model of the human RPE [ 9 , 11 , 12 ]. Recently, it was also reported that a TRPM2 channel naturally exists in ARPE19 cells [ 16 , 27 ]. These factors led us to choose the cells used in the current investigation, which were a gift from Professor Suat Erdoğan (Trakya University, Edirne, Turkey).…”

“…In the images of ARPE19 that were stained with 1 µM Fluo 3/AM (at dark for 60 min) (ThermoFisher Sci. ), we measured the cCa 2+ concertation [ 16 , 25 ]. Axio Observer 7 inverted microscope with 20 × objective (Carl-Zeiss) was attached to the LSM-800 setup for the laser stimulation of the Fluo 3/AM in the labeled cells.…”

“…Stimulation of the transient receptor potential melastatin 2 (TRPM2) channels in ARPE19 cells by a number of drugs, including bevacizumab [ 11 ] and cisplatin [ 15 ], has been reported to cause adverse oxidative and apoptotic effects. However, these negative effects have been counteracted by the use of TRPM2 channel antagonists, including carvacrol (CRV) and N-(p-amylcinnamoyl)anthranilic acid (ACA) [ 12 , 13 , 16 ], as well as antioxidants, such as CRC and glutathione [ 11 , 15 ]. The involvement of TRPM2 has not been reported in HCQ-mediated overload cCa 2+ influx and mROS generation in ARPE19 cells.…”

“…The influx of Ca 2+ modulates the physiological functions of retinal cells [ 17 ]. However, increased mROS production and apoptosis are induced by elevated Ca 2+ accumulation within the mitochondria via the activation of TRPM2 in ARPE19 cells [ 12 , 13 , 15 , 16 ]. CRC is a bright-yellow material produced by plants of the Curcuma longa genus.…”