ABSTRACT
The aim of this study is to assess the oxidative stress status in diabetes mellitus (DM) and diabetic nephropathy. The study group comprised 40 control subjects, 40 type 2 DM patients without complications and 37 diabetic nephropathies. Compared with control subjects, superoxide dismutase, glutathione peroxidase, catalase, vitamin C were decreased (P < 0.01). There was a significant increase in serum malondialdehyde (MDA), conjugated diene (CD), advanced oxidation protein products (AOPP), protein carbonyl (PC) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in diabetes patients when compared with normal subjects (P < 0.01). Moreover, these indexes were much higher in diabetic nephropathy than that of diabetic patients without vascular complications (P < 0.05, P < 0.01). There was a significant correlation between the serum glucose levels and PC, 8-OHdG (P < 0.05, P < 0.01). There were highly significant positive correlation of CD and MDA, AOPP and PC (P < 0.01). Plasma AOPP levels had a significant correlation with PC levels (P < 0.01). Our findings suggested that diabetes patients have more severe oxidative stress than normal persons and higher oxidative stress in diabetic nephropathy than those in patients without complications. Oxidative stress may play an important intermediary role in the pathogenesis of diabetes complications.
Subject(s)
Diabetes Mellitus, Type 2/metabolism , Diabetic Nephropathies/metabolism , Oxidative Stress , 8-Hydroxy-2'-Deoxyguanosine , Adult , Aged , Case-Control Studies , Catalase/metabolism , Deoxyguanosine/analogs & derivatives , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/enzymology , Diabetic Nephropathies/enzymology , Diabetic Nephropathies/etiology , Female , Glutathione/blood , Glutathione Peroxidase/metabolism , Humans , Male , Malondialdehyde/blood , Middle Aged , Superoxide Dismutase/metabolismABSTRACT
AIM: To examine the effect of pseudolaric acid B on the growth of human gastric cancer cell line, AGS, and its possible mechanism of action. METHODS: Growth inhibition by pseudolaric acid B was analyzed using MTT assay. Apoptotic cells were detected using Hoechst 33258 staining, and confirmed by DNA fragmentation analysis. Western blot was used to detect the expression of apoptosis-regulated gene Bcl-2, caspase 3, and cleavage of poly (ADP-ribose) polymerase-1 (PARP-1). RESULTS: Pseudolaric acid B inhibited the growth of AGS cells in a time- and dose-dependent manner by arresting the cells at G(2)/M phase, which was accompanied with a decrease in the levels of cdc2. AGS cells treated with pseudolaric acid B showed typical characteristics of apoptosis including chromatin condensation and DNA fragmentation. Moreover, treatment of AGS cells with pseudolaric acid B was also associated with decreased levels of the anti-apoptotic protein Bcl-2, activation of caspase-3, and proteolytic cleavage of PARP-1. CONCLUSION: Pseudolaric acid B can dramatically suppress the AGS cell growth by inducing apoptosis after G(2)/M phase arrest. These findings are consistent with the possibility that G(2)/M phase arrest is mediated by the down-regulation of cdc2 levels. The data also suggest that pseudolaric acid B can trigger apoptosis by decreasing Bcl-2 levels and activating caspase-3 protease.
