title: Elucidation of mechanisms underlying the protective effects of olive leaf extract against lead-induced neurotoxicity in Wistar rats.
abstract: Recently, we identified that olive leaf extract (OLE) prevents lead (Pb)-induced abnormalities in behavior and neurotransmitters production in chronic Pb exposure in rats. The aim of the present study was to provide additional evidence that OLE acts as an anti-apoptotic, anti-inflammatory, and antioxidant mediator in Pb exposed rats. 4-weeks old Wistar rats were exposed or not to 250 mg/l Pb for 13-weeks and then exposed to tap water containing or not 0.1% OLE for additional 2-weeks. Atomic absorption spectrophotometry showed significantly elevated Pb levels in the hippocampus and serum and reaches 5 and 42 µg/mg tissue, respectively. In the hippocampus, the examination of markers of apoptosis and inflammation revealed an increase in caspase-3 activity and DNA fragmentation as well as tumor necrosis factor alpha, interleukin-1 beta and prostaglandin E2 in Pb-exposed rats. In addition, our findings showed that Pb induced 4-hydroxynonenal production and inhibited antioxidant-related enzyme activity, such as glutathione-S-transferase as wells as energy metabolism-related enzyme activity, such as NADP-isocitrate dehydrogenase and glucose transporter. Upon examination of signaling pathways involved in apoptosis process, we found that Pb induced p38 mitogen activated protein kinase (MAPK) and Akt phosphorylation, but in contrast, inhibited that of ERK(1/2). Interestingly, OLE administration diminished tissue Pb deposition and prevented all Pb effects. In the frontal cortex, our data also showed that OLE-abolished Pb-induced caspase-3 activity and DNA fragmentation. Collectively, these data support the use of OLE by traditional medicine to counter Pb neurotoxicity.
authors: Département de Biologie, Faculté des Sciences, Université d'Es-Senia, Oran, Algeria.
authors: Leila
authors: L
authors: Seddik
authors: Thierno Madjou
authors: TM
authors: Bah
authors: Abdelkader
authors: A
authors: Aoues
authors: Miloud
authors: M
authors: Slimani
authors: Mohamed
authors: M
authors: Benderdour
mesh_terms: D000447:Aldehydes / Q000097:blood; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D015232:Dinoprostone / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D031658:Olea / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000447:Aldehydes; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D007854:Lead; D007521:Isocitrate Dehydrogenase; C039355:isocitrate dehydrogenase (NADP+); D005982:Glutathione Transferase; D053148:Caspase 3; C027576:4-hydroxy-2-nonenal; D015232:Dinoprostone