Lysosomal membrane permeabilization (LMP) has been shown to cause the release of cathepsins and other hydrolases from the lysosomal lumen to the cytosol and initiate a cell death pathway. Whether proteinuria triggers LMP in renal tubular epithelial cells (TECs) to accelerate the progression of renal tubulointerstitial injury remains unclear. In the present study, we evaluated TEC injury as well...

It has already been reported that muscle necrosis induced by various phenylenediamine derivatives are correlated with their autoxidation rate. Now in a more detailed investigation of the cytotoxic mechanism using a model system of isolated hepatocytes and ring-methylated structural isomer durenediamine (DD) we have shown that under aerobic conditions, phenylenediamine induced cytotoxicity and R...

6- Mercaptopurine (6-MP) is widely used in clinic as an immunosuppressive for treatment of acute lymphocytic leukemia, Crohn's disease, and ulcerative colitis with documented unpredictable hepatotoxicity. The potential molecular cytotoxic mechanisms of 6-MP against isolated rat hepatocytes were searched in this study using “Accelerated Cytotoxicity Mechanism Screening (ACMS)” techniques. The co...

BACKGROUND AND PURPOSE Endogenous neuroprotection can be induced by ischemic and nonischemic preconditioning. However, not all subjects that undergo preconditioning exhibit similar favorable outcome. This study is to explore the molecules responsible for this phenomenon and find new therapeutic targets for stroke. METHODS Adult male Sprague-Dawley rats were subjected to transient middle cereb...

BACKGROUND Procyanidins are apple constituents with potential in colon cancer chemoprevention. MATERIALS AND METHODS Human colon cancer derived metastatic cells (SW620), growing under standardized conditions, were exposed to procyanidins and lysosomotropic compounds. Growth, apoptosis and lysosomal integrity was determined using published methods. RESULTS Lysosomotropic drugs (MDL 72527, ph...

The Arp2/3-activator Wiskott-Aldrich syndrome protein and Scar homologue (WASH) is suggested to regulate actin-dependent membrane scission during endosomal sorting, but its cellular roles have not been fully elucidated. To investigate WASH function, we generated tamoxifen-inducible WASH-knockout mouse embryonic fibroblasts (WASHout MEFs). Of interest, although EEA1(+) endosomes were enlarged, c...

Dog and rat hepatocytes were treated with phospholipogenics to identify the more sensitive species and to determine whether lysosomal or mitochondrial changes were the primary cause of cytotoxicity. Endpoints included cell death, lysosome membrane integrity, mitochondrial membrane polarization, and fluorescent phospholipid (NBD-PE). Dog cells exhibited lower survival IC50 values than did rat ce...

The cytotoxicity of oxidized LDL (oxLDL) to several types of artery wall cells might contribute to atherosclerosis by causing cell death, presumably by both apoptosis and necrosis. After its uptake into macrophage lysosomes by receptor-mediated endocytosis, oxLDL is poorly degraded, resulting in ceroid-containing foam cells. We studied the influence ofoxLDL on lysosomal enzyme activity and, in ...

background: exposure to arsenic is associated with impairment of male reproductive function by inducing oxidative stress. silymarin with an antioxidant property scavenges free radicals. objective: the aim of this study was to investigate if silymarin can prevent the adverse effects of sodium arsenite on ram sperm plasma membrane and acrosome integrity. materials and methods: ram epidydimal sper...

semen quality and its relationship to fertility are major concern in animal production. the aim of this study was to assess the relationship between frozen thawed sperm characteristics and fertility following in vivo fertility through artificial insemination(ai). semen samples were collected from four buffalo bulls. semen volume and sperm concentration appeared to be significantly different (p0...