Resveratrol attenuates 4-hydroxy-2-hexenal-induced oxidative stress in mouse cortical collecting duct cells

Resveratrol (RSV) may provide numerous protective eff ects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the eff ects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, p47(phox), Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced NF-κB activation by promoting IκB-α degradation. Meanwhile, the observed increases in nuclear NF-κB, NOX4, p47(phox), and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting NF-κB activation.

Increased Phosphorylation of PI3K/Akt/mTOR in the Obstructed Kidney of Rats with Unilateral Ureteral Obstruction / 전남의대학술지

The present study aimed to investigate changes in the mammalian target of rapamycin (mTOR) signaling pathway in the obstructed kidney of rats with unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were unilaterally obstructed by ligation of the left proximal ureter for 7 days. Control rats were treated in the same way except that no ligature was made. The expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, and mTOR were determined in the kidney by semiquantitative immunoblotting. The protein expression levels of transforming growth factor (TGF)-beta1, Bax, and Bcl-2 were also determined in the kidney. The phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of ureteral obstruction rats compared with the control. In the obstructed kidney, the protein expression of TGF-beta1 and Bax was also increased, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the obstructed kidney of rats with UUO.

Increased Phosphorylation of PI3K/Akt/mTOR in the Obstructed Kidney of Rats with Unilateral Ureteral Obstruction / 전남의대학술지

The present study aimed to investigate changes in the mammalian target of rapamycin (mTOR) signaling pathway in the obstructed kidney of rats with unilateral ureteral obstruction (UUO). Male Sprague-Dawley rats were unilaterally obstructed by ligation of the left proximal ureter for 7 days. Control rats were treated in the same way except that no ligature was made. The expression levels of phosphorylated phosphatidylinositol 3-kinase (PI3K), Akt, and mTOR were determined in the kidney by semiquantitative immunoblotting. The protein expression levels of transforming growth factor (TGF)-beta1, Bax, and Bcl-2 were also determined in the kidney. The phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of ureteral obstruction rats compared with the control. In the obstructed kidney, the protein expression of TGF-beta1 and Bax was also increased, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the obstructed kidney of rats with UUO.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Activation of the Renal PI3K/Akt/mTOR Signaling Pathway in a DOCA-Salt Model of Hypertension / 전남의대학술지

The present study investigated the changes that occurred in the mammalian target of rapamycin (mTOR) signaling pathway in the kidney as a result of deoxycorticosterone acetate (DOCA)-salt hypertension. Rats were implanted with DOCA strips (200 mg/kg) 1 week after unilateral nephrectomy and were then supplied with 0.9% saline to drink. Four weeks after DOCA implantation, systolic blood pressure (SBP) was measured by use of the tail-cuff method. The expression levels of phosphorylated phosphatidylinositol-3-kinase (PI3K), Akt, and mTOR, as well as the protein expression levels of ED-1 and cyclooxygenase-2 (COX-2), transforming growth factor-beta1 (TGF-beta1), alpha-smooth muscle actin (SMA), caspase-3, Bax, and Bcl-2, were then examined in the kidney by semiquantitative immunoblotting. DOCA-salt hypertensive rats were found to have significantly increased SBP as well as an increased kidney weight-to-body weight ratio. Moreover, the phosphorylation of PI3K, Akt, and mTOR was increased in the kidney of DOCA-salt hypertensive rats compared with the control, as was the protein expression of ED-1, COX-2, TGF-beta1, and alpha-SMA. The expression levels of caspase-3 and Bax were increased significantly, whereas Bcl-2 expression was decreased. In conclusion, the phosphorylation of PI3K/Akt/mTOR was increased in the kidney of DOCA-salt hypertensive rats.

Inhibitory Effects of 6-Gingerol on Cytochrome P450 in Human Liver Microsomes

No abstract available.

The Protective Effect of Curcumin on Myocardial Ischemia-Reperfusion Injury

BACKGROUND AND OBJECTIVES: Myocardial ischemia-reperfusion (I/R) injury is one of the major causes of cardiac mortality. Curcumin, an active component extracted from turmeric in curry, inhibits inflammatory responses. This study was designed to investigate whether curcumin can exert beneficial effects on myocardial I/R injury. MATERIALS AND METHODS: Sprague-Dawley male rats received a normal diet or a curcumin diet (80 mg/kg/d) for one week, and I/R injury was induced by ligating the left anterior descending artery (LAD) for 30 min followed by release. After 24 hours, the myocardium was extracted to evaluate the myeloperoxidase (MPO) activity and the vascular cellular adhesion molecule (VCAM)-1 protein level. The apoptotic cardiomyocytes and neutrophils were counted and quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining at 14 days after I/R. RESULTS: In the infarcted myocardium of the curcumin-fed rats, the MPO activity (32.9+/-2.2% of the control, p=0.001) and the VCAM-1 protein (28.7+/-2.9% of control, p=0.001) level were significantly attenuated. The number of neutrophils was lower in the curcumin-fed rats (57+/-12% of the control, p=0.024). A reduction of the apoptotic cardiomyocytes was also observed in the curcumin-fed I/R rats (36+/-9.2% of the control, p=0.032). CONCLUSION: The cardioprotective effects of curcumin on an I/R injury rat model could include anti-inflammation activities and inhibition of apoptosis that occurred in the cardiomyocytes. Our findings suggest that curcumin has a positive contribution as a dietary supplement for the prevention of heart disease.

Effects of Mesenchymal Stem Cells on Stress Incontinence in a Rat Model / 대한비뇨기과학회지

PURPOSE: Several study trials have used stem cells to treat stress incontinence in an animal model. In this study, we compared injecting either periurethral mesenchymal stem cells(MSC) or normal saline(C) to increase the leak point pressure(LPP) and closing pressure(CP) in a rat model of stress urinary incontinence. MATERIALS AND METHODS: Sprague Dawley rats(250g each, 12 weeks old) were divided into the MSC group(n=5) and group C(n=5). They were anesthetized and the pudendal nerve was transected bilaterally via a ventral incision in order to denervate the external urethral sphincter. The MSCs were obtained from both femurs of Sprague Dawley rats(150g each, 6 weeks, n=10). After 1 week, the MSCs were stained by 4'-6-diamidino- 2-phenylindole(DAPI), which was injected into both sites of the proximal external urethra(n=1.5x10(6)). At 3 weeks after injection, cystometry was performed and this was followed by cord transection at the T9-10 level with the rat under anesthesia. Visually identified LPP and CP measurements were evaluated with using a vertical tilt/intravesical pressure clamp. The urethral tissues of the rats were harvested for histology. RESULTS: Both the LPP and CP measurements were significantly higher in the MSC group when compared with that of the C group(p<0.05). The mean LPP of the MSC group and group C was 42.3+/-2.1cmH2O and 25.8+/-1.7cmH2O, respectively. The mean CP of the MSC group and group C was 31.7+/-2.5cmH2O and 21.3+/-1.1cmH2O, respectively. The existence of DAPI-stained MSCs in the injected periurethral tissue was verified by histology after the completion of the study. CONCLUSIONS: Injection of MSCs into the periurethal tissue after transection of the bilateral pudendal nerve in rats led to an increase in the LPP and CP. This finding suggests that MSCs can be used as one of the potentially effective cell therapies for stress urinary incontinence.

Effects of Mesenchymal Stem Cells on Stress Incontinence in a Rat Model / 대한비뇨기과학회지

PURPOSE: Several study trials have used stem cells to treat stress incontinence in an animal model. In this study, we compared injecting either periurethral mesenchymal stem cells(MSC) or normal saline(C) to increase the leak point pressure(LPP) and closing pressure(CP) in a rat model of stress urinary incontinence. MATERIALS AND METHODS: Sprague Dawley rats(250g each, 12 weeks old) were divided into the MSC group(n=5) and group C(n=5). They were anesthetized and the pudendal nerve was transected bilaterally via a ventral incision in order to denervate the external urethral sphincter. The MSCs were obtained from both femurs of Sprague Dawley rats(150g each, 6 weeks, n=10). After 1 week, the MSCs were stained by 4'-6-diamidino- 2-phenylindole(DAPI), which was injected into both sites of the proximal external urethra(n=1.5x10(6)). At 3 weeks after injection, cystometry was performed and this was followed by cord transection at the T9-10 level with the rat under anesthesia. Visually identified LPP and CP measurements were evaluated with using a vertical tilt/intravesical pressure clamp. The urethral tissues of the rats were harvested for histology. RESULTS: Both the LPP and CP measurements were significantly higher in the MSC group when compared with that of the C group(p<0.05). The mean LPP of the MSC group and group C was 42.3+/-2.1cmH2O and 25.8+/-1.7cmH2O, respectively. The mean CP of the MSC group and group C was 31.7+/-2.5cmH2O and 21.3+/-1.1cmH2O, respectively. The existence of DAPI-stained MSCs in the injected periurethral tissue was verified by histology after the completion of the study. CONCLUSIONS: Injection of MSCs into the periurethal tissue after transection of the bilateral pudendal nerve in rats led to an increase in the LPP and CP. This finding suggests that MSCs can be used as one of the potentially effective cell therapies for stress urinary incontinence.

Curcumin Attenuates Nuclear Factor-kappaB, c-Jun N-Terminal Kinase and p38 in Tumor Necrosis Factor-alpha-Stimulated Endothelial Cells

BACKGROUND AND OBJECTIVES: Curcumin, a yellow pigment of turmeric in curry, has been reported to interfere with nuclear factor (NF)-kappaB. This study was designed to investigate the underlying pathway of the anti-inflammation effect of curcumin on endothelial cells. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor (TNF)-alpha (10 ng/mL). The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, and the adhesion of U-937 monocytes to the HUVECs was then examined. Nuclear factor kappa B (NF-kappaB) activation was determined by the NF-kappaB p65 translocation to the nucleus via immunocytochemistry. The expression of the NF-kappaB dependent pro-inflammatory molecules were measured by RT-PCR and ELISA. The phosphorylations of c-Jun N-terminal protein kinase (JNK), p38 and STAT-3 (signal transducer and activator of transcription-3) were measured by Western blotting. RESULTS: Curcumin blocked the activation of NF-kappaB by TNF-alpha, and it also reduced the ROS, monocyte adhesion and the phosphorylation of JNK, p38 and STAT-3 in the TNF-alpha-stimulated HUVECs. The expression of intracellular cell adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8 were attenuated by curcumin at both the transcription and translation levels. CONCLUSION: We suggest that curcumin could contribute to protection against the adverse vascular effects of the pro-inflammatory response through the modulation of NF-kappaB, JNK, p38 and STAT-3, and this is in addition to its antioxidant effect in endothelial cells.

Carvedilol Inhibits Expressions of Vascular Cell Adhesion Molecule-1, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant-1, and Interleukin-8 via NF-kappaB Inhibition in Human Endothelial Cells

BACKGROUND AND OBJECTIVES: Carvedilol is an anti-oxidative, the cardioprotective effects of which are mediated by the inhibition of NF-kappaB activation. The present study was designed to examine the effects of carvedilol, an alpha1- and beta-blocker, on tumor necrosis factor (TNF)-alpha stimulated human umbilical vein endothelial cells (HUVEC). Materials and METHODS: HUVEC were treated with TNF-alpha (10 ng/mL) in either the absence or presence of carvedilol. The levels of intracellular reactive oxygen species (ROS) were examined using a fluorescent dye DCFH-DA, with the adhesion of U-937 monocyte to the HUVEC. Nuclear factor kappa B (NF-kappaB) activation was determined by NF-kappaB p65 translocation to the nucleus using Western blotting and immunocytochemistry. The expressions of NF-kappaB dependent pro-inflammatory molecules, i.e., vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-8, were measured by RT-PCR and ELISA. Bcl-2 and phosphorylation of c-Jun N-terminal protein kinase (JNK) were measured using Western blotting. RESULTS: TNF-alpha treatment increased the activation of NF-kappaB, suppressed Bcl-2, and increased the phosphorylation of JNK, the ROS level and the adhesion of U-937. The levels of mRNA and protein expressions of VCAM-1, ICAM-1, MCP-1 and IL-8 were up-regulated by TNF-alpha. Carvedilol inhibited the phosphorylation of JNK, ROS formation and the adhesion of U-937 monocyte. In addition, carvedilol reduced the production of VCAM-1, ICAM-1, MCP-1 and IL-8 at the mRNA and protein levels, via the suppression of NF-kappaB activation. CONCLUSION: These results suggested that the anti-inflammatory effects of carvedilol on TNF-alpha stimulated endothelial cells could be explained by its ROS-scavenging and NF-kappaB inactivation properties.