Bradykinin protects against DDP-induced GP-H1 cell damage via activation of PI3K/Akt/NO signaling pathway.

OBJECTIVE: To investigate the effect of bradykinin (BK) on cisplatin (DDP)-induced cardiotoxicity at the cellular level and its cytological mechanism. METHODS: The toxic effects of DDP on GP-H1 cells, and the effects of BK on DDP cardiomyocyte survival rate, DDP-induced malondialdehyde (MDA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), reactive oxygen species (ROS), mitochondria membrane potential (MMP) and apoptosis were explored. RESULTS: DDP at different concentrations inhibited GP-H1 cells at 12 h after administration, and the inhibitory effect was more prominent at 24 h after administration and continued until 72 h after administration. The severity of GP-H1 cell damage induced by DDP was reduced by 0.1 µM, 1 µM, and 10 µM BK. After GP-H1 cells were treated with DDP, ROS levels increased and MMP levels decreased, while BK intervention inhibited these effects. At 24 h after DDP treatment, Bax/bcl-2 increased in GP-H1 cells, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. After intervention with BK, it was shown that Bax/Bcl-2 was significantly reduced, and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 decreased. Bax/Bcl-2 and the expressions of Caspase-3, p-NF-κB, p-p38 and p-Smad2 of GP-H1 cells were basically not affected by BK alone. CONCLUSION: The protective effect of BK on DDP-induced GP-H1 cell damage in guinea pig is related to the activation of PI3K/Akt/NO signaling pathway by BK, which reduces oxidative stress levels in cardiomyocytes and also acts as an anti-apoptotic agent.

[Effects of human peritoneal mesothelial cells on angiogenesis factor expression and secretion of ovarian carcinoma cells].

OBJECTIVE: To investigate the impact of human peritoneal mesothelial cells (HPMC) on angiogenesis factor expression and secretion of ovarian carcinoma cell line SKOV3. METHODS: The conditioned medium with HPMC was tested by ELISA for tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-1beta). Millicell was used to co-culture HPMC and ovarian carcinoma cell line SKOV3 in the presence or absence of neutralizing antibody against TNF-alpha or IL-1beta. RT-PCR was used to detect vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) gene expression in SKOV3 cells. VEGF and bFGF protein levels in the SKOV3 conditioned medium were assessed by ELISA. RESULTS: Conditioned medium with HPMC contained both TNF-alpha and IL-1beta. SKOV3 co-cultured with HPMC expressed higher levels of VEGF and bFGF mRNA and secreted at increased levels of both VEGF and bFGF, in comparison with those in SKOV3 cells cultured alone (P < 0.01). Addition of neutralizing antibody against TNF-alpha or IL-1beta during co-cultures resulted in decrease in mRNA expression and secretion of VEGF and bFGF in SKOV3 cells. When both antibodies were administered during co-culture, additive decrease was observed. CONCLUSION: HPMC can act in a paracrine fashion to stimulate ovarian tumor cells to produce and secret at increased levels of VEGF and bFGF through TNF-alpha and IL-1beta, and contribute to angiogenesis and peritoneal metastasis of ovarian cancer.

[Maternal plasma leptin levels and their relationship to insulin and glucose in pregnant women with gestational diabetes mellitus and gestational impaired glucose tolerance].

OBJECTIVE: To investigate the changes in leptin levels and the relationship between the substance and insulin and glucose in pregnant women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT). METHODS: Radio immunoassay was used to measure the leptin levels at fasting and 3 h after oral glucose load (50 g) in 36 patients with GDM and GIGT, and also in 24 normal pregnant women. In each pregnant women, fasting serum insulin levels and glycosylated haemoglobin values were measured by electrochemiluminescent immunoassays and pressure liquid chromatography (LPLC) respectively, glucose levels 1 h after the administration of glucose by glucose oxidase method. RESULTS: The serum leptin levels in pregnant women with GDM and GIGT and normal pregnant women were (14.9 +/- 4.3) micro g/L and (10.0 +/- 1.8) micro g/L, respectively, suggesting the serum leptin levels were significantly higher in pregnant women with GDM and GIGT than in normal controls. The levels of fasting serum insulin, glycosylated haemoglobin values and plasma glucose levels obtained 1h after oral administration of 50 g glucose were (12.9 +/- 4.3) mU/L, (6.1 +/- 1.1)%, (11.0 +/- 1.4) mmol/L, respectively, whereas the corresponding values in normal controls were (8.6 +/- 3.2) mU/L, (4.5 +/- 1.0)%, (7.8 +/- 1.2) mmol/L. A positive correlation was found between maternal serum leptin levels and fasting serum insulin levels in pregnant women with GDM and GIGT (r = 0.835, P < 0.01). A positive correlation was also found between maternal leptin concentrations and glycosylated haemoglobin values, as well as between leptin levels and plasma glucose levels obtained 1 h after the administration of 50g glucose in women with GDM and GIGT (r = 0.758, P < 0.01; r = 0.561, P < 0.01). CONCLUSIONS: Leptin levels are elevated in pregnant women with GDM and GIGT compared with healthy pregnant women, a positive and significant correlation was found between the maternal leptin levels and fasting insulin levels, as well as between the maternal leptin levels and plasma glucose levels obtained 1 h after the administration of 50 g glucose in women with GDM and GIGT.