Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat. (December 2015)

• Record Type: Journal Article
• Authors: Moallem, Seyed Adel; Mohamadpour, Amir Hooshang; Abnous, Khalil; Sankian, Mojtaba; Sadeghnia, Hamid Reza; Tsatsakis, Aristidis; Shahsavand, Shabnam
• Is Part Of: Food and chemical toxicology. Volume 86(2015)
• Page Start: 56
• Page End: 64
• Publication Date: 2015-12
• Subjects: Carbon monoxide poisoning -- Erythropoietin -- Myelin basic protein -- Glial fibrillary acidic protein -- Myeloperoxidase -- Neurotoxicity; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2015.09.015
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver–Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10, 000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10, 000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning. Graphical abstract: Highlights: EPO reduces the mortality rate after CO poisoning. EPO reduces brain BAX/Bcl-2 ratio and myelin basic protein alteration in a rat model of CO poisoning. EPO reduces malondialdehyde levels and MPO activity in brain and GFAP in the serum. EPO could not reduce the water content of the edematous poisoned brains. However it protects the blood brain barrier. After histological staining, fewer vacuoles and demyelinated fibers were found in the EPO-treated animals.