MK-8931 mg The soluble receptor for advanced glycation end p

The soluble receptor for advanced glycation end products has been already studied in physiological and pathological pregnancy. In accordance to our previous studies we showed increased sRAGE serum levels in women with threatening premature labor [15] and we described a negative correlation of sRAGE with the leucocyte count [14]. Increased sRAGE serum levels in preeclampsia has been already described [14], [16], [32], however higher sRAGE serum levels in preeclampsia are not fully understood. Next to previously described sRAGE correlation with serum creatinine and serum uric MK-8931 mg levels [14] we found, that sRAGE correlates positively with daily proteinuria. Uric acid is newly understood as a part of the pathophysiological mechanism of preeclampsia due to uric acid’s ability to promote inflammation, oxidative stress and endothelial dysfunction [33]. Uric acid is as well regarded as an indicator of severity of preeclampsia. Serum creatinine levels reflect kidney function. Because of these facts and our findings of positive correlation of sRAGE with uric acid serum levels, creatinine serum levels and daily proteinuria, we might hypothesize that sRAGE levels are probably changing along with the severity of preeclampsia. Our study did not show affected sRAGE serum levels in patients with IUGR. The most often reason of IUGR is placental dysfunction. The state is accompanied by oxidative stress as well [34], however, in our study sRAGE serum levels were not influenced by this chronic state of organism. sRAGE has not been studied in patients with ICP till now. ICP is characterized as increased liver enzymes (ALT and AST) after exclusion of other causes of hepatopathy. Bile acids are elevated in ICP as well [35]. Secondary bile acid and deoxycholic acid, increases in serum of ICP patients, too. Fujii et al. found that deoxycolic acid affects the secretion of HMGB1 protein, RAGE ligand, in intestinal epithelial cells [36]. Anticipating that elevating ALT and AST serum levels are associated with increased bile acid levels in ICP, the negative correlation of sRAGE with ALT, can be caused by the consumption of sRAGE by HMGB1. AST tends to correlate negatively with sRAGE serum as well, however this trend was not statistically significant. sRAGE serum levels are not affected in ICP in comparison to controls, however the studied group of patient with ICP is small and further study is needed to clarify the results.
Conclusions Our study did not find any association of RAGE gene polymorphisms (RAGE −429 T/C, −374 T/A, 2184 A/G, Gly82Ser) or glyoxalase I gene (GLO1 A419C) polymorphisms with pathological pregnancy. We showed an association of GA genotype of RAGE Gly82Ser polymorphism with lower sRAGE serum levels in healthy pregnant women. Newly we studied sRAGE serum level in women with IUGR and ICP, but we did not discover varied sRAGE concentrations in the patients, anyway we demonstrated negative correlation of serum sRAGE with serum ALT levels. However genetic as well as biochemical analyses are influenced with a small number of subjects, so further studies with a larger number of patients with pathological pregnancy are needed to confirm our results.
Conflict of interest
Acknowledgments The study was supported by the grant GAUK259080 50409 and research projects SVV-2012-264511 and PRVOUK-P25/LF1/2. The authors are thankful to MSc. Jana Švarcová, Mrs. Hudcová, Mrs. Řeháková, Mrs. Pourová and Mrs. Němcová for technical assistance.
Numerous experimental and clinical evidences, , , , , demonstrate that some of the non-steroidal anti-inflammatory drugs (NSAIDs), especially indomethacin, can enhance the cytotoxicity of a variety of anticancer drugs when co-administered. One possible explanation of their anti-cancer effect is that they might come into effect via a cyclooxygenase-independent pathway, in which the enzymatic activity of human glyoxalase I (GLOI) is inhibited by indomethacin with a value of 18.1μM (comparable to its inhibitory affinity of 5μM towards COX-2)., It is proposed that indomethacin is able to restore apoptosis in cancer cells by binding to GLOI. As a ubiquitous detoxification pathway, GLOI (EC 4.4.1.5) along with glyoxalase II removes highly reactive α-oxoaldehydes, thus protects against cellular damage caused by glycation reactions., Abnormal expression or higher activity of GLOI has been determined in colon, prostate, lung, and resistant human leukemia cells. Such over-expression or elevated activity of GLOI is involved in apoptosis resistance to anti-tumor agents in cancer cells., It is shown by many in vitro and in vivo studies that inhibitors of GLOI are promising agents in inhibiting carcinogenesis and overcoming drug resistance by inducing elevated concentrations of methylglyoxal in cancer cells., ,