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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Parameshwaran, Kodeeswaran Irwin, Michael H. Steliou, Kosta Pinkert, Carl A. |
| Description | Country affiliation: United States Author Affiliation: Parameshwaran K ( Department of Pathobiology, College of Veterinary Medicine, Auburn University, AL 36849, United States. paramko@auburn.edu) |
| Abstract | Exposure to environmental toxins, including rotenone, results in central nervous system and systemic toxicity. Rotenone is a widely used pesticide and a mitochondrial complex I (CI) inhibitor. This study reports effectiveness of a synthetic lipoylcarnitine antioxidant compound, lipoylcarnitine methyl ester iodide (PMX-500F), for treatment of chronic rotenone induced neurological deficits in mice. Mice (C57BL/6NTac; two months of age) received oral administration of rotenone (30 mg/kg/day) or vehicle, preceded by intraperitoneal injection of PMX-500F (19 mg/kg) or vehicle for four weeks. In the Rota-rod test, rotenone treatment had no effect (P>0.05); however, PMX-500F treatment improved locomotor coordination and endurance (latency to fall time; P<0.05). For neuromuscular strength (wire hang test), rotenone treated mice showed reduced latency to fall compared to control mice (P<0.05). PMX-500F treatment improved the outcome in both control and rotenone exposed mice (P<0.05). Rotenone administration increased ROS generation in the forebrain and midbrain regions, but not in the cerebellum (P<0.05). Co-treatment with PMX-500F normalized the ROS in forebrain and midbrain regions to that of the control concentrations. In rotenone administered mice, activated stress-activated protein kinase/c-Jun NH2-terminal kinase (pSAPK/JNK) was higher in forebrain and midbrain lysates than in control mice (P<0.05) and treatment with PMX-500F reduced pSAPK/JNK to control levels. The pSAPK/JNK levels in the cerebellum were similar in all four groups (P>0.05). Total SAPK/JNK was not altered by either rotenone or PMX-500F treatment (P>0.05). These results illustrate that an antioxidant, here PMX-500F, provides protection against rotenone induced decline in neuromotor function, reactive oxygen species (ROS) generation and cellular stress. |
| File Format | HTM / HTML |
| ISSN | 00913057 |
| Issue Number | 3 |
| Volume Number | 101 |
| e-ISSN | 18735177 |
| Journal | Pharmacology Biochemistry and Behavior |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-05-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Behavioral Sciences Discipline Biochemistry Discipline Pharmacology Antioxidants Pharmacology Brain Drug Effects Metabolism Rotenone Toxicity Animals Electron Transport Complex I Antagonists & Inhibitors Hazardous Substances Insecticides Map Kinase Signaling System Mice Mice, Inbred C57bl Motor Skills Neuroprotective Agents Reactive Oxygen Species Stress, Physiological Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Biological Psychiatry Behavioral Neuroscience Biochemistry Clinical Biochemistry Toxicology Pharmacology |
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