Carnitine Enigma: From Antioxidant Action to Vitagene Regulation. Part 1. Absorption, Metabolism, and Antioxidant Activities

L-carnitine (LC) is a small water-soluble molecule playing an important role in fat metabolism and there is a growing interest in the potential uses of LC as a medicinal agent and as a nutritional/dietary supplement. In addition to a great interest from medical sciences, carnitine received a substantial attention from pig and poultry industry. In particular, poultry and pig diets are formulated mainly with plant feed ingredients which are poor sources of carnitine. Furthermore, internal carnitine synthesis depends on many factors and in some cases could be inadequate. Therefore, it seems likely that carnitine dietary supplementation of highly productive and/or stressed animals/ birds is of great importance. The molecular mechanisms accounting for the positive effects of LC on farm animals and poultry are not yet determined but many protective effects of LC reported in literature have been related to its antioxidant action. Based on literature review it is concluded that there are several important mechanisms of antioxidant action of carnitine. Firstly, carnitine is shown to directly scavenge free radicals. However, this activity is most likely related to the gut antioxidant defences and has limited relevance to target tissues with relatively low carnitine concentrations. Secondly, carnitine can chelate transition metals (Fe 2+ and Cu + ), preventing their participation in ROS formation via Fenton reaction. However, detailed mechanisms of this process should be further elucidated using modern techniques applied to various biological systems. Again, this carnitine action is very much related to the gut. Thirdly, and more importantly, LC is found to decrease free radical formation by inhibiting specific enzymes (e.g. xanthine oxidase and NADPH oxidase) responsible for free radical production. This carnitine action has a high biological relevance in various stress conditions. Fourthly, and most importantly, carnitine is shown to participate in maintaining the integrity of mitochondria, including electron-transport chain of mitochondria, in stress conditions. Indeed, carnitine can be considered as a mitochondria-specific antioxidant, responsible for mitochondria integrity maintenance and regulation of ROS production and ROS signalling. Fifthly, carnitine can affect vitamin E absorption and metabolism improving the total antioxidant systems. There are important additional mechanisms of carnitine AO activity, including activation/inhibition of various transcription factors and vitagene networks. Antioxidant activities of carnitine in physiologically relevant concentrations have been well demonstrated in various in vitro systems including cell cultures or isolated cells or organelles. Protective effect of LC and its derivatives on the antioxidant systems of the body are also shown in various models of oxidative stress/toxicity caused by a variety of toxicants and neurotoxic agents. Several lines of evidence from animal experiments and clinical studies indicate that LC supplementation is effective in preventing oxidative stress under various pathological conditions (hypoxia, ischemia-reperfusion, ionizing radiation, hypertension, renal failure and drug-induced nephrotoxicity, over-exercising and ageing) and in patients with various diseases. Antioxidant protective effects were shown by using