RESUMEN
Macrophage infiltration is one of the main pathological features of ulcerative colitis (UC) and ferroptosis is a type of nonapoptotic cell death, connecting oxidative stress and inflammation. However, whether ferroptosis occurs in the colon macrophages of UC mice and whether targeting macrophage ferroptosis is an effective approach for UC treatment remain unclear. The present study revealed that macrophage lipid peroxidation was observed in the colon of UC mice. Subsequently, we screened several main components of essential oil from Artemisia argyi and found that ß-caryophyllene (BCP) had a good inhibitory effect on macrophage lipid peroxidation. Additionally, ferroptotic macrophages were found to increase the mRNA expression of tumor necrosis factor alpha (Tnf-α) and prostaglandin-endoperoxide synthase 2 (Ptgs2), while BCP can reverse the effects of inflammation activated by ferroptosis. Further molecular mechanism studies revealed that BCP activated the type 2 cannabinoid receptor (CB2R) to inhibit macrophage ferroptosis and its induced inflammatory response both in vivo and in vitro. Taken together, BCP potentially ameliorated experimental colitis inflammation by inhibiting macrophage ferroptosis. These results revealed that macrophage ferroptosis is a potential therapeutic target for UC and identified a novel mechanism of BCP in ameliorating experimental colitis.
Asunto(s)
Colitis Ulcerosa , Colitis , Ferroptosis , Ratones , Animales , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Sesquiterpenos Policíclicos/farmacología , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Inflamación/tratamiento farmacológico , Sulfato de DextranRESUMEN
Dermal exposure to chemicals released from daily consumer products is a rising concern, particularly for children who are susceptible to unintentional hand-to-mouth transfer and related chemical exposure risk. However, chemical transfer induced by tiny particles of intact products has yet to be adequately addressed. The objective of the present study was to determine the potentiality of particles release from intact erasers and pen grips upon dermal contact by measuring the migration rates of the embedded plasticizers (phthalates and its alternatives). The results showed that billions of particles were released from erasers (0.6-1.2 × 109) and pen grips (0.2-1.6 × 108) upon dermal contact at ambient temperature, with sizes mainly smaller than 1 µm. The composition of eraser leachates was identical to that of the corresponding bulk eraser, as confirmed by Fourier-transform infrared spectroscopy and pyrolysis. Migrated hydrophobic plasticizers may be used as indicators of particle release from erasers and pen grips. The potentiality of particle release was negatively correlated with the total plasticizer contents (r = -0.51; p < 0.05) for both erasers and pen grips. These findings indicated that particles directly released from school supplies and accessories could be a non-negligible source of human exposure to plasticizers.