title: Apitoxin protects rat pups brain from propionic acid-induced oxidative stress: The expression pattern of Bcl-2 and Caspase-3 apoptotic genes.
abstract: The primary aim of this study was to determine the potential modulatory role of the apitoxin (bee venom; BV) against propionic acid (PPA)-induced neurotoxicity. The biochemical responses to PPA exposure in rat pups were assayed, including changes in the antioxidant barrier systems and lipid peroxidation and protein oxidation biomarkers in the brain tissue. DNA damage was measured by single-cell gel electrophoresis and differences in Bcl-2 and Caspase-3 mRNA expression were assessed using real-time PCR. Changes in amygdala complex ultrastructure were visually assessed using electron microscopy. Sixty rat pups were assigned into six groups: a control group, a PPA-treated group, a BV-treated group, a protective co-treated group, a therapeutic co-treated group, and a protective/therapeutic co-treated group. The results indicate that PPA induced a pronounced increase (64.6%) in malondialdehyde (MDA), and in DNA damage (73.3%) with three-fold increase in protein carbonyl concentration. A significant reduction was observed in the enzyme activities of superoxide dismutase (SOD) (48.7%) and catalase (CAT) (74.8%) and reduced glutathione (GSH) level (52.6%). BV significantly neutralized the PPA-induced oxidative stress effects, especially in the BV protective/therapeutic co-treated group. In this group, GSH levels were restored to 64.5%, and MDA, protein carbonyl levels and tail moment % were diminished by 69.5, 21.1 and 18.8% relative to the control, respectively. Furthermore, while PPA induced significant apoptotic neural cell death, BV markedly inhibited apoptosis by promoting Bcl-2 expression and blocking Caspase-3 expression. BV markedly restored the normal ultrastructural morphology of the amygdala complex neurons. These results conclusively demonstrate that BV administration provides both protective and therapeutic effects in response to the PPA-induced deleterious effects, including oxidative stress, DNA damage, and neuronal death in the brains of rat pups.
authors.affiliation: Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.
authors.forename: Samah R
authors.initials: SR
authors.lastname: Khalil
authors.affiliation: Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Zagazig University, Egypt.
authors.forename: Yasmina M
authors.initials: YM
authors.lastname: Abd-Elhakim
authors.affiliation: Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; Zoology Department, Faculty of Science, Ain Shams University, Cairo, Egypt. Electronic address: manar.selim@hotmail.com.
authors.forename: Manar E
authors.initials: ME
authors.lastname: Selim
authors.affiliation: Physiology Department, Faculty of Medicine, King Saud University, Autism Research and Treatment Centre, AL-Amodi Autism Research Chair, Riyadh, Saudi Arabia.
authors.forename: Laila Y
authors.initials: LY
authors.lastname: Al-Ayadhi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001514:Bee Venoms / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011422:Propionates / Q000494:pharmacology*; D050050:Protein Carbonylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001514:Bee Venoms; D011422:Propionates; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D005978:Glutathione; C029658:propionic acid
keywords: Amygdala; Bee venom; Comet assay; Neural cell death; Oxidative stress Propionic acid