nitrophenols and Necrosis

Platelet lifespan is limited by activation of intrinsic apoptosis. Apoptotic platelets are rapidly cleared from the circulation in vivo. ABT-737 triggers platelet apoptosis and is a useful tool for studying this process. However, in vitro experiments lack clearance mechanisms for apoptotic platelets. To determine whether apoptotic platelets progress to secondary necrosis, apoptosis was triggered in human platelets with ABT-737, a BH3 mimetic. Platelet annexin V (AnV) binding, release of AnV

Topics: Animals; Apoptosis; Biphenyl Compounds; Blood Platelets; Calcimycin; Calcium; Caspase Inhibitors; Caspases; Cells, Cultured; Down-Regulation; Extracellular Vesicles; Humans; Mice; Necrosis; Nitrophenols; Phosphatidylserines; Piperazines; Platelet Activation; Signal Transduction; Sulfonamides

Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo.. Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption. In both ABT-737 (apoptotic) and agonist (necrotic)-treated platelets, phosphatidylserine externalization was temporally correlated with IMM disruption. Agonist stimulation resulted in rapid cyclophilin D-dependent IMM disruption that coincided with phosphatidylserine exposure. ABT-737 treatment caused rapid cytochrome c release, eventually followed by caspase-dependent IMM disruption that again closely coincided with phosphatidylserine exposure. A nonmitochondrial and integrin-mediated mechanism has been implicated in the formation of a novel phosphatidylserine-externalizing platelet subpopulation. Using image cytometry, this subpopulation is demonstrated to be the result of the interaction of an aggregatory platelet and a procoagulant platelet rather than indicative of a novel intracellular mechanism regulating platelet phosphatidylserine externalization. Using electron microscopy, similar interactions between aggregatory and procoagulant platelets are demonstrated in vitro and in vivo within a mesenteric vein hemostatic thrombus.. Platelet phosphatidylserine externalization is closely associated with the mitochondrial event of IMM disruption identifying a common pathway in phosphatidylserine-externalizing platelets. The limited interaction of procoagulant platelets and integrin-active aggregatory platelets identifies a potential mechanism for procoagulant platelet retention within the hemostatic thrombus.

Topics: Animals; Apoptosis; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Biphenyl Compounds; Blood Coagulation; Blood Platelets; Caspases; Crotalid Venoms; Cyclophilins; Cytochromes c; Disease Models, Animal; Genotype; Integrins; Kinetics; Lectins, C-Type; Mice, Knockout; Mitochondria; Mitochondrial Membranes; Necrosis; Nitrophenols; Peptidyl-Prolyl Isomerase F; Phenotype; Phosphatidylserines; Piperazines; Platelet Aggregation; Signal Transduction; Sulfonamides; Thrombin; Venous Thrombosis

4-nitrophenol (PNP) is generally regarded as a diesel exhaust particle (DEP). Arginine plays an important role as a new feed additive, possessing highly efficient antioxidant activities. Here we investigated the effects of dietary supplementation with arginine against ovarian damage induced by PNP in rats. A total of thirty-two female rats postnatal day 28 (PND 28) were randomly divided into four groups. Two groups were fed with basal diet or 13 g/kg arginine in diet for 4 weeks, respectively; the other two groups were given PNP (100 mg/kg b.w.) daily by subcutaneous injection for 2 weeks following pretreatment with either basal diet or arginine diet for 2 weeks. The values of body weight gain (BWG), average daily gain (ADG) and percentage weight gain (PWG) upon PNP treatment were significantly reduced than those in other groups. The relative liver weight in the PNP group was significantly decreased compared with the control group. Treatment with PNP significant reduced the number of corpora lutea, although serum 17β-estradiol (E2) and progesterone (P4) concentrations were unchanged. The morphology of the ovaries in PNP-treated rats displayed necrosis, follicular deformation and granulosa cells irregular arrangement. Moreover, exposure to PNP enhanced production of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and decreased the activities of total superoxide dismutase (T-SOD) and catalase (CAT), and the co-administration of arginine can attenuate the oxidative stress caused by PNP. These results suggest that arginine may have a protective effect against ovarian damage induced by PNP owing to its antioxidant capacity effect.

Topics: Animals; Antioxidants; Arginine; Biomarkers; Catalase; Cytoprotection; Estradiol; Female; Hydrogen Peroxide; Malondialdehyde; Necrosis; Nitrophenols; Ovarian Follicle; Ovary; Oxidative Stress; Progesterone; Rats, Sprague-Dawley; Superoxide Dismutase

Topics: Animals; Anthelmintics; Biotransformation; Chemical Phenomena; Chemistry; Dinitrophenols; Dogs; Necrosis; Nitrophenols; Rats

Topics: Animals; Cholinesterase Inhibitors; Diaphragm; Isoflurophate; Necrosis; Neuromuscular Junction; Nitrophenols; Phosphates; Pralidoxime Compounds; Rats; Tubocurarine