Ulinastatin suppresses endoplasmic reticulum stress and apoptosis in the hippocampus of rats with acute paraquat poisoning

• Main Authors: Hai-feng Li, Shi-xing Zhao, Bao-peng Xing, Ming-li Sun
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2015-01-01
• Series: Neural Regeneration Research
• Subjects: tamoxifen; Src kinase; PP2; trauma; regeneration; neuroprotection; auranofin; dextromethorphan; rosiglitazone; Alzheimer′s disease; neuroinflammation; neurodegeneration; microglia; astrocytes; nerve regeneration; spinal cord; electroacupuncture therapy; neural stem cells; notch signaling pathway; inflammation; survival curve; proliferation; differentiation; real-time quantitative PCR; western blot assay; neural regeneration; superparamagnetic iron oxide; magnetic guidance; bone marrow mesenchymal stem cells; spinal cord injury; cell transplantation; magnetic resonance image; lumbar puncture; spinal cord transection; average combined score; magnetic resonance imaging; diffusion tensor imaging; fractional anisotropy; apparent diffusion coefficient; fiber tractography; peripheral nerve injury; sciatic nerve; hypothermia; blood-nerve barrier; Evans blue tracer; neural degeneration; polyethyleneimine-polyethylene glycol; spiral ganglion cells; X-linked inhibitor of apoptosis protein; gene therapy; nanocarrier; cisplatin; ototoxicity; cochlea; ocular hypertension; JNK3; retinal ganglion cell; glaucoma; laser photocoagulation; intraocular pressure; brain injury; apoptosis; cerebral ischemia; SMAD3; transforming growth factor β1; NSFC grant; Chinese herbal formula; Tneurotrophic factor; ongluo Jiunao injection; nerve growth factor receptor; Xuesai Tong; hippocampus; dentate gyrus; lipid peroxidation; type 1 diabetes; malondialdehyde; neurons; acupuncture; cerebral hemorrhage; immunohistochemistry; Notch1; Hes1; rats; DAPT; transcranial direct current stimulation; visuomotor coordination; task difficulty; primary motor area; motor learning; paraquat; poisoning; endoplasmic reticulum stress; ulinastatin; CHOP; GRP78; caspase-3; reactive oxygen species
• Online Access: http://www.nrronline.org/article.asp?issn=1673-5374;year=2015;volume=10;issue=3;spage=467;epage=472;aulast=Li

Lung injury is the main manifestation of paraquat poisoning. Few studies have addressed brain damage after paraquat poisoning. Ulinastatin is a protease inhibitor that can effectively stabilize lysosomal membranes, prevent cell damage, and reduce the production of free radicals. This study assumed that ulinastatin would exert these effects on brain tissues that had been poisoned with paraquat. Rat models of paraquat poisoning were intraperitoneally injected with ulinastatin. Simultaneously, rats in the control group were administered normal saline. Hematoxylin-eosin staining showed that most hippocampal cells were contracted and nucleoli had disappeared in the paraquat group. Fewer cells in the hippocampus were concentrated and nucleoli had disappeared in the ulinastatin group. Western blot assay showed that expressions of GRP78 and cleaved-caspase-3 were significantly lower in the ulinastatin group than in the paraquat group. Immunohistochemical findings showed that CHOP immunoreactivity was significantly lower in the ulinastatin group than in the paraquat group. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining showed that the number of apoptotic cells was reduced in the paraquat and ulinastatin groups. These data confirmed that endoplasmic reticular stress can be induced by acute paraquat poisoning. Ulinastatin can effectively inhibit this stress as well as cell apoptosis, thereby exerting a neuroprotective effect.