RESUMO
Bone cancer pain (BCP) is a common pathologic pain associated with destruction of bone and pathological reconstruction of nervous system. Current treatment strategies in clinical is inadequate and have unacceptable side effects due to the unclear pathology mechanism. In the present study, we showed that transplantation of Walker 256 cells aggravated mechanical allodynia of BCP rats (**p < 0.01 vs. Sham), and the expression of ASIC3 (Acid-sensitive ion channel 3) and TRPV1 was obviously enhanced in L4-6 dorsal root ganglions (DRGs) of BCP rats (**p < 0.01 vs. Sham). ASIC3 and TRPV1 was mainly expressed in CGRP and IB4 positive neurons of L4-6 DRGs. While, TRPV1 but not ASIC3 was markedly upregulated in L4-6 spinal dorsal horn (SDH) of BCP rats (**p < 0.01 vs. Sham). Importantly, intrathecal injection of CPZ (a TRPV1 inhibitor) or Amiloride (an ASICs antagonist) markedly increased the paw withdraw threshold (PWT) of BCP rats response to Von Frey filaments (**p < 0.01 vs. BCP + NS). What's more, intraperitoneally injection of Metformin or Vinorelbine markedly elevated the PWT of BCP rats, but reduced the expression of TRPV1 and ASIC3 in L4-6 DRGs and decreased the TRPV1 expression in SDH (*p < 0.05, **p < 0.01 vs. BCP + NS). Collectively, these results suggest an effective analgesic effect of Metformin on mechanical allodynia of BCP rats, which may be mediated by the downregulation of ASIC3 and TRPV1.
RESUMO
Concentrations and composition of six organophosphate esters (OPEs) in drinking water in the Weifang Binhai Economic-Technological Development Area were detected by solid phase extraction-gas chromatography-triple quadrupole mass spectrometry (SPE-GC-MS/MS). The correlations of OPEs in drinking water and pooled serum samples from the Weifang Binhai Economic-Technological Development Area were analyzed. The health risk posed by OPEs in drinking water was evaluated using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA). The results showed that ∑6OPEs concentrations in the tap water samples ranged from 162-253 ng·L-1, while ∑6OPEs concentrations in groundwater ranged from 3.52-13.9 ng·L-1, two orders of magnitude lower than that in the tap water. Tris(2-chloroethyl)phosphate (TCEP) was the dominant OPE in the tap water samples, with the median level accounting for 94.81% of the ∑6OPEs. Triphenyl phosphate (TPhP) was the dominant OPE in groundwater, with the median level accounting for 47.55% of the ∑6OPEs. The composition of OPEs in the human mixed serum collected in 2011 and 2015 was strongly correlated with that in the tap water (r=0.990, P<0.01 and r=0.997, P<0.01, respectively). This indicates the significant contribution of OPEs in drinking water to OPEs in human serum. The daily intake (DI) of OPEs via drinking water was 0.26-7.48 ng·(kg·d)-1 and the non-cancer risk hazard quotient (HQ) of OPEs in drinking water ranged from 10-5.81-10-2.43, indicating a negligible non-cancer risk to the local residents exposed to OPEs through drinking water. The carcinogenic risks posed by TCEP in drinking water ranged from 10-8.82-10-6.79, which was lower than the theoretical threshold (Risk=10-6.00), while the carcinogenic risk of TCEP in tap water was higher than that in groundwater.