Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-kappaB Pathways

This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-kappaB), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-alpha), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-kappaB, COX-2, iNOS, TNF-alpha, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-kappaB, COX-2, iNOS, TNF-alpha, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-kappaB and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

Determinants of Responsiveness of LDL-cholesterol Lowering to Lifestyle Modification in Hypercholesterolemic Patients / 가정의학회지

BACKGROUND: Current guidelines for the treatment of hyperlipidemia propose lifestyle modification as a first-line intervention. The aim of this study was to identify the factors which determine responsiveness of LDL-cholesterol lowering to lifestyle modification in hypercholesterolemic patients. METHODS: A total of 109 patients aged between 30 and 70 years (52 men and 109 women) who were diagnosed with hypercholesterolemia between July 2007 and February 2008 at Asan Medical Center were enrolled in this study. The patients were educated on lifestyle modifications by trained family physicians. We measured clinical, anthropometric, lifestyle parameters and lipid profiles initially and at eight weeks after education. Stepwise multiple linear regression models were used to assess covariates and variance components. RESULTS: The serum level of LDL-cholesterol decreased in both women (8.0 +/- 15.37%, P < 0 .001) and men (4.95 +/- 9.81%, P < 0.001). In women, dietary adherence (beta = 0.267, P = 0.004), change in physical activity duration (beta = 0.196, P = 0.034) and menopausal state (beta = -0.207, P = 0.026) were significant predictors in response of percent change in LDL-cholesterol. In men, dietary adherence (beta = 0.372, P = 0.007) was a predictor in response of percent change in LDL-cholesterol. CONCLUSION: Adherence to lifestyle modification was a main factor which had influenced on response of percent change in LDL-C levels. In women, however, menopausal state was also an important factor.