The Preventive and Therapeutic Effects of Aronox Extract on Metabolic Abnormality and Hypertension

BACKGROUND: Aronox is an anthocyanin-rich extract from Aronia melanocarpa E which is known to have anti-inflammatory effect in atherosclerosis due to high anti-oxidative activity. This study was conducted to evaluate the preventive and therapeutic effect of Aronox on hypertension and metabolic status in spontaneously hypertensive rats (SHR). METHODS: Seven-week-old male SHR were orally administrated with Aronox (low dose; 100 mg/kg, n = 4 or high dose; 200 mg/kg, n = 3) or amlodipine (10 mg/kg, n = 7) and sham (n = 10) for 8 weeks. Aronox was administered 30 mg/kg for the first 3 weeks and then increased to 100 mg/kg (low dose group) or 100 mg/kg to 200 mg/kg (high dose group). Systolic blood pressure (SBP) was measured every week by tail cuff method. At 8 weeks, fasting lipid level was measured. Heart and kidney stained with Masson's trichrome. RESULTS: Aronox or amlodipine treatment showed significantly lower SBP compared with sham (202.2 +/- 10.2 mm Hg in low dose group, 202.0 +/- 12.6 mm Hg in high dose group and 187.4 +/- 22.7 mm Hg in amlodipine group vs. 224.4 +/- 12 mm Hg in sham-SHR, p < 0.005). There were no significant differences in cardiac and renal weight corrected by body weight among 3 groups. Aronox and amlodipine treatments significantly decreased fasting glucose and showed a trend of decrease in triglyceride level. Aronox or amlodipine treatment for 8 weeks showed less collagen deposition changes compared to sham. CONCLUSIONS: Aronox showed significant antihypertensive effects, decreased fasting glucose, and less cardiac and renal fibrosis in SHR. These results suggest that Aronox can be used as an adjuvant therapy or functional food in hypertension.

Expression of NAD(P)H Oxidase Subunits and Their Contribution to Cardiovascular Damage in Aldosterone/Salt-Induced Hypertensive Rat

NAD(P)H oxidase plays an important role in hypertension and its complication in aldosterone-salt rat. We questioned whether NAD(P)H oxidase subunit expression and activity are modulated by aldosterone and whether this is associated with target- organ damage. Rats were infused with aldosterone (0.75 microgram/hr/day) for 6 weeks and were given 0.9% NaCl+/-losartan (30 mg/kg/day), spironolactone (200 mg/kg/ day), and apocynin (1.5 mM/L). Aldosterone-salt hypertension was prevented completely by spironolactone and modestly by losartan and apocynin. Aldosterone increased aortic NAD(P)H oxidase activity by 34% and spironolactone and losartan inhibited the activity. Aortic expression of the subunits p47(phox), gp91(phox), and p22(phox) increased in aldosterone-infused rats by 5.5, 4.7, and 3.2-fold, respectively, which was decreased completely by spironolactone and partially by losartan and apocynin. Therefore, the increased expression of NAD(P)H oxidase may contribute to cardiovascular damage in aldosterone-salt hypertension through the increased expression of each subunit.

Polymorphisms in ERCC1 and ERCC2/XPD and Survival in Non-Small-Cell Lung Cancer Patients Treated with Cisplatin Based Chemotherapy

PURPOSE: The expressions of low levels of ERCC1 (excision repair crosscomplementation group 1) and ERCC2/XPD (excision repair cross- complementation group 2) have been studied in order to find a potential marker for predicting the prognosis or treatment response in cancer patients. However, polymorphisms in these genes have been rarely evaluated in terms of predicting the survival of cancer patients. MATERIALS AND METHODS: We investigated whether these polymorphisms had an effect on the response to chemotherapy and on the survival in 109 patients, with non-small-cell lung cancer, treated with cisplatin plus gemcitabine, paclitaxel or docetaxel. The polymorphisms of ERCC1 Asn118Asn (C->T), ERCC2 Lys751Gln and Asp312Asn were evaluated using a SNaPshot kit. RESULTS: The treatment responses showed no statistically significant differences according to the polymorphisms of ERCC1 Asn118Asn, ERCC2 Lys751Gln or Asp312Asn. The median survival time was 376 days (95% CI, 291~488). The overall survival rate showed no significant difference according to age, sex, chemotherapy regimen, clinical stage or sequential radiation therapy. The polymorphisms of ERCC2 Lys751Gln and Asp312Asn did not affect the survival of the patients (p=0.4711 and 0.4542, respectively). The polymorphism of ERCC1 Asn118Asn, chemotherapy response, performance status and body weight loss had effect on the overall survival of the patients (p=0.0001, 0.0001, 0.0176 and 0.0082 respectively). As for survival rate, according to the polymorphism in ERCC1 Asn118Asn, the median survival time in those patients showing the wild genotype (C/C) was 480 days (95% CI, 333~544), which was statistically significant compared with the 281 days for the patients with the variant genotype (T/T, C/T) (hazard ratio 3.497) (95% CI, 214~376). CONCLUSION: It is suggested that the presence of the wild genotype in ERCC1 Asn118Asn, in non-small-cell lung cancer patients treated with cisplatin based chemotherapy, was a surrogate marker for predicting a better survival.

Reduction of TNF alpha-induced oxidative DNA damage product, 8-hydroxy-2'-deoxyguanosine, in L929 cells stably transfected with small heat shock protein

Previous studies have demonstrated that oxidative stress involving generation of reactive oxygen species (ROS) is responsible for the cytotoxic action of TNF alpha. Protective effect of small heat shock proteins (small HSP) against diverse oxidative stress conditions has been suggested. Although overexpression of small hsp was shown to provide an enhanced survival of TNF alpha-sensitive cells when challenged with TNF alpha, neither the nature of TNF alpha-induced cytotoxicity nor the protective mechanism of small HSP has not been completely understood. In this study, we have attempted to determine whether TNF alpha induces oxidative DNA damage in TNF alpha-sensitive L929 cells. We chose to measure the level of 8-hydroxy-2'-deoxyguanosine (8 ohdG), which has been increasingly recognized as one of the most sensitive markers of oxidative DNA damage. Our results clearly demonstrated that the level of 8 ohdG increased in L929 cells in a TNF alpha dose-dependent manner. Subsequently, we asked whether small HSP has a protective effect on TNF alpha-induced oxidative DNA damage. To accomplish this goal, we have stably transfected L929 cells with mouse small hsp cDNA (hsp25) since these cells are devoid of endogenous small hsps. We found that TNF alpha-induced 8 ohdG was decreased in cells overexpressing exogenous small hsp. We also found that the cell killing activity of TNF alpha was decreased in these cells as measured by clonogenic survival. Taken together, results from the current study show that cytotoxic mechanism of TNF alpha involves oxidative damage of DNA and that overexpression of the small hsp reduces this oxidative damage. We suggest that the reduction of oxidative DNA damage is one of the most important protective mechanisms of small HSP against TNF alpha.