الفهرس 
Chapter IOnly 14 pages are availabe for public view
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Abstract
In addition to their metabolic roles, LC posses unique neuroprotective, neuromodulatory, and neurotrophic properties coming from their neurophysiological roles that are relevant in counteracting various disease processes. L-C is an energy carrier through the mitochondrial inner membranes, controlling the availability of acetyl-CoA, and sustaining the activity of the respiratory chain complex. L-Carnitine is potentially an attractive therapeutic modality for perinatal asphyxia given the extensive pediatric clinical experience with the use of this drug in epilepsy, inborn errors of metabolism, and cardiomyopathy (O’Donnell et al., 2002). Virmani et al., (2002) have showed a protective effect of L-carnitine on the methamphetamine neurotoxicity, mediated by peroxinitrite radicals. L-carnitine was reported to improve several neurotoxicities induced by uncoupler of mitochondrial phosphorylation such as 3-nitro-propionic acid (an inhibitor of the succinate dehydrogenase) (Binienda, 2003). Yapar et al., (2007) have demonstrated a protective effect of L-carnitine on the hexachlorophene neurotoxicity in mice. A large body of evidences indicates that LC prevents and/or ameliorates mitochondrial dysfunction caused by a series of conditions either in vivo or in vitro (Silva-Adaya et al., 2008; Zhang et al., 2010). LC pretreatment was able to inhibit pilocarpine-induced seizures, SE and mortality of adult rats (Ahmed and Mahmoud, 2012). LC plays a crucial role in the translocation of acetyl moieties from the mitochondria into the cytoplasm for acetylcholine (Ach) synthesis in the brain (Rani and Panneerselvam, 2001).
The cytoprotective effects of carnitine in various stress conditions are believed to be due to a decrease in oxidative stress-related cell damages. Recent review clearly showed that LC can inhibit main ROS-producing enzymes, namely xanthine oxidase (XO) and NADPH oxidase and in this way contributing to improved antioxidant defence systems (Surai, 2015).
Clear evidence of carnitine protective effect against oxidative damage caused by various chemicals came from in vitro studies with cell culture, isolated cells or organelles. This includes human dermal fibroblasts (Dhaunsi et al., 2004), cerebellar granular cell culture (Tastekin et al., 2005), LDL (Augustyniak et al., 2008), human hepatocytes (Li et al., 2012), cultured porcine oocytes (Yazaki et al., 2013), neuroblastoma cells (Ye et al., 2014) and neurones of newly born rats (Liu et al., 2013). LC was also able to decrease DNA damage caused by toxicants in various experimental systems (Mescka et al., 2014; Liu et al., 2014; Deon et al., 2015). Effective LC concentrations showing antioxidant protective effects were within the physiological range of LC concentrations varying from 9-25 μM (Yazaki et al., 2013), 30-100 μM (Liu et al., 2013), 0.1-1 mM (Li et al., 2012; Ye et al., 2014) up to 1-10 mM (Tastekin et al., 2005).
Protective effect of LC and its derivatives were shown in decreasing oxidative stress caused by neurotoxic agents such as glutamate (Nagesh et al., 2011), quinolinic acid or 3-nitropropionic acid (Elinos-Calderón et al., 2009), pilocarpine, rotenone (Zaitone et al., 2012), dexamethasone (Assaf et al., 2012), aminoglycosides (Jafari et al., 2013), scopolamine (Wang et al., 2014), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Loots et al., 2004) and silver nano-particles (Liu et al., 2015).