title: alpha-Tocopherol modifies lead induced functional changes at murine neuromuscular junction.
abstract: Lead impacts neuromuscular junction and might induce skeletal muscle weakness. Antioxidants may prevent toxic actions of lead on muscle. In this study, resting membrane potentials, endplate potentials, miniature endplate potentials (MEPPs) and isometric twitch tensions were recorded to investigate effects of alpha-tocopherol (Vitamin E) on lead induced changes at murine dorsiflexor muscle. Moreover, levels of endplate nicotinic receptors were measured by receptor autoradiography. Forty rats were divided into four groups (lead alone, alpha-tocopherol, lead plus alpha-tocopherol and saline). Lead (1 mg/kg, i.p.), was administered daily for 2 weeks and alpha-tocopherol (100 mg/kg, i.p.) was given daily for 3 weeks. Lead treatment significantly reduced twitch tension (from 4.4+/-0.4 to 2.2+/-0.3 g) and delayed half time of decay. MEPP frequencies and quantal content were also significantly reduced after lead treatment. Pretreatment with alpha-tocopherol reversed twitch tension reduction (4.1+/-0.3 g) and modified lead induced delay in half time of decay. Similarly, alpha-tocopherol modified the negative actions of lead exposure on MEPP frequencies and quantal content. Receptor autoradiographic studies revealed significant increase of nicotinic receptor levels at the endplate region of flexor muscle in lead treated mice. However, animals treated with lead plus alpha-tocopherol showed significantly decreased levels of nicotinic receptors. alpha-Tocopherol appears to protect against lead induced neuromuscular dysfunction. These effects of alpha-tocopherol are possibly mediated via a free radical mechanism or modification of calcium homeostasis.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, UAE University, Al-Ain, United Arab Emirates.
authors.forename: M Y
authors.initials: MY
authors.lastname: Hasan
authors.forename: W B
authors.initials: WB
authors.lastname: Alshuaib
authors.forename: A
authors.initials: A
authors.lastname: Adem
authors.forename: S
authors.initials: S
authors.lastname: Singh
authors.forename: M A
authors.initials: MA
authors.lastname: Fahim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D007854:Lead / Q000037:antagonists & inhibitors* / Q000097:blood / Q000633:toxicity; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000737:chemistry; D009469:Neuromuscular Junction / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D024502:alpha-Tocopherol / Q000097:blood / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D018696:Neuroprotective Agents; D011978:Receptors, Nicotinic; D007854:Lead; D024502:alpha-Tocopherol