Tetrandrine-induced apoptosis in rat primary hepatocytes is initiated from mitochondria: caspases and endonuclease G (Endo G) pathway.

Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra (S Moore), possesses a remarkable pharmacological profile. However, the mechanisms of tetrandrine hepatotoxicity remain to be elucidated. In this study, we first proved apoptosis and mitochondrial dysfunction induced by tetrandrine in Sprague-Dawley rat liver in vivo. By further assuming apoptosis as an important mechanism in tetrandrine-induced hepatotoxicity, we focused on mitochondria-initiated apoptosis in primary hepatocytes isolated from Sprague-Dawley male rats. Tetrandrine treatment led to significant release of cytochrome c and downregulation of Bcl-X(L) accompanied by caspase 3 activation, and ultimately, DNA fragmentation. Caspase 3 activation was markedly inhibited by cyclosporin A (CsA) and Ac-DEVD-CHO. Furthermore, Endo G, a caspase-independent apoptotic protein, was detected for its expression and DNase activity. CsA blocked the release both of Endo G and cytochrome c significantly. Additionally, the generation of reactive oxygen species (ROS) increased in a time-dependent manner corresponding with a fall in intracellular GSH content after 10 microM tetrandrine treatment in 4h. Tetrandrine also induced mitochondrial dysfunction indicated by transition of mitochondrial transmembrane potential and decrease of intracellular ATP level. The findings indicated that the caspase-dependent mitochondrial apoptosis pathway was primarily involved in tetrandrine-induced apoptosis in rat primary hepatocytes. In addition, a caspase-independent pathway indicated by Endo G also contributed to apoptosis caused by tetrandrine. Meanwhile, ROS was proved an important inducer in this apoptosis process.

Advanced oxidation protein products induce monocyte chemoattractant protein-1 expression via p38 mitogen-activated protein kinase activation in rat vascular smooth muscle cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Advanced oxidation protein products (AOPPs) are new uremic toxins reported by Witko-Sarsat in 1996, which are associated with the pathogenesis of atherosclerosis. However, the mechanisms by which AOPPs enhance atherosclerosis have not been fully understood. Monocyte chemoattractant protein-1 (MCP-1) is a chemokine which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. In this study, we investigated the effect of AOPPs on MCP-1 expression in cultured vascular smooth muscle cells (VSMCs).</p><p><b>METHODS</b>VSMCs were cultured and then co-incubated with AOPP (200 micromol/L, 400 micromol/L) for different times with or without pretreatment with specific p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. RT-PCR and Western blott were used to detect MCP-1 mRNA and protein expression at different time points after AOPP stimulation in rat smooth muscle cells. Western blot was used to detect the expression of phosphorylated p38 MAPK.</p><p><b>RESULTS</b>Treatment of VSMC with AOPPs resulted in a significant increase of the expression of MCP-1 mRNA and protein in time- and dose-dependent manner, and could activated p38 MAPK. Pretreatment of VSMCs with SB203580 resulted in a dose-dependent inhibition of AOPPs-induced MCP-1 mRNA and protein expression.</p><p><b>CONCLUSIONS</b>AOPPs can stimulate MCP-1 expression via p38 MAPK in VSMCs. This suggests that AOPPs might contribute to the formation of atherosclerosis through this proinflammatory effect.</p>

Effects of the second renal transplantation on the sexual function of kidney recipients / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of the second renal transplantation on sexual function.</p><p><b>METHODS</b>Thirty kidney graft recipients, including 29 cases of the second renal transplantation and 1 case of simultaneous dual kidney transplantation, responded to the questionnaire. The penis cavernosal artery flow of these patients were examined by color doppler ultrasonography. Of the 30 recipients, 9 underwent bilateral kidney transplantation with their bilateral external iliac arteries anastomosed to the donors' renal arteries (Group A), 10 recipients with their unilateral external iliac arteries and the other internal iliac arteries anastomosed to the donors' renal arteries (Group B), the other 10 with their internal iliac arteries anastomosed to the donors' renal arteries (Group C).</p><p><b>RESULTS</b>Eight recipients of Group A, 7 of Group B, and 5 of Group C were restored to normal sexual function 6 months after kidney transplantation. The peak systole velocity (PSV) in Group C was slower than in Groups A and B.</p><p><b>CONCLUSION</b>Kidney transplantation with the second internal iliac arteries anastomosed to donors' renal arteries may affect the sexual function of the recipients, but some might enjoy satisfactory sexual life some time after the establishment of lateral branch circulation.</p>