Carnitine Enigma: From Antioxidant Action to Vitagene Regulation. Part 2. Transcription Factors and Practical Applications

Abstract

A growing interest has been shown in the potential uses of carnitine in medical practice and animal/poultry industry. The molecular mechanisms accounting for the positive effect of LC on livestock animals are not yet fully understood but many protective effects of LC in various stress conditions reported in literature, have been related to its antioxidant action. Based on the analysis of the recent publications presented in the review it could be concluded that antioxidant actions of carnitine are associated to much extent with redox signaling in the cell. Indeed, LC is shown to upregulate Nrf2 and PPARs and downregulates NF-κB leading to anti-apoptotic and anti-inflammation actions of carnitine. In fact, Nrf2-mediated synthesis of antioxidant enzymes, including SOD, GSH-Px, GR, GST and GSH, in response to carnitine supplementation could be a main driving force of antioxidant action of carnitine and its derivatives. Furthermore, LC and its derivatives are shown to affect vitagene networks resulting in increased adaptive ability to stresses via additional synthesis of protective molecules, including heat shock proteins (HO-1), upregulating sirtuins, thioredoxins and SOD. It seems likely that in biological system in vivo the interactions of the aforementioned mechanisms provide an important place for carnitine to be a crucial part of the integrated antioxidant systems of the animal and human body. Furthermore, direct scavenging ROS and chelating properties of carnitine would be very much relevant to the antioxidant system of the gut. Taking into account low carnitine content in grains and poultry and pig diet formulations with limited amounts of animal proteins, carnitine requirement and possible inadequacy in commercial poultry and pig nutrition should receive more attention. Furthermore, protective roles of carnitine in stress conditions of commercial poultry and pig production, including its immunomodulating properties, are of great importance. Therefore, a development of carnitine-containing antioxidant compositions supplying via drinking water seems to be an important way forward in decreasing the detrimental consequence of various stresses in poultry and pig production.

Antioxidant Defence Systems and Oxidative Stress in Poultry Biology: An Update

“…This was associated with increased mRNA expression of antioxidant genes (Nrf2, HO-1, SOD, CAT, GPx) and decreased the oxidative damage index (MDA, ROS, PC, 8-OhdG) in chicken breast muscle [296] and expression of Nrf2, HO-1, SOD and GPx in chicken liver mitochondria due to the dietary probiotic [297]. Furthermore, there is a range of other nutrients upregulating Nrf2 expression in different poultry tissues, including carnitine [90], taurine [298] and silymarin [91].…”

“…Once the ROS/RNS production exceeds the ability of the antioxidant defence system to neutralise them, oxidative stress occurs and important biological molecules, including polyunsaturated fatty acids (PAFAs), proteins and DNA can be damaged leading to detrimental consequences in terms of health, growth and development of poultry. Therefore, the antioxidant defence includes several options [13,15,[88][89][90][91][92][93][94] (Figure 1): Figure 1. Antioxidant defence mechanisms (adapted from Reference [13]).…”

“…Indeed, the vitagene concept was further developed and validated in relation to poultry production [13,[89][90][91][92]112,113,179]. Accumulating experimental evidence indicates that there is a great opportunity to nutritionally modulate the vitagene network using various nutritional supplements, including phytochemicals [176], carnitine, [90,180], betaine, taurine and vitamins A, E and D [13,181]. In fact, activation of the vitagene network by nutritional means is considered a new fundamental approach for improving animal/poultry resistance to various stresses [13,111].…”

Effect of L-Carnitine on Oxydative Stress at Cardiovascular Diseases

“…Кроме того, LC входит в систему адаптации клеток сердца и сосудов к неблагоприятным условиям и разным видам стрессов, а также влияет на внутриклеточные редокс-чувствитеьные сигнальные процессы, мишенью действия которых выступают ключевые факторы транскрипции генов, ответственные за активацию или ингибирование экспрессии генов, продукты которых регулируют в т. ч. состояние оксидативного стресса при хронических патологиях сердца и сосудов. Все это свительствует о широком круге активности LC и его производных, использование которых является одним из новых подходов регуляции активности клеток сердца и сосудов при ишемии/реперфузии и других видах стрессов [28,29].…”

“…В условиях стресса или стимуляции факторами роста активация Nrf2 влияет на увеличенное образование радикалов кислорода в МХ через усиление транскрипции белка-разобщителя-3, а также воздействия на биогенез МХ благодаря увеличению уровней ядерного дыхательного фактора-1 и коактиватора 1 рецептора- активируемого пролифератором пероксисом (PPAR-), а также усиления синтеза пуриновых нуклеотидов. Фармакологические активаторы Nrf2, например изотиоцианат сульфорафана (isothiocyanate sulforaphane), ингибирует оксидант-зависимое открывание mPTP и тем самым предупреждает набухание и разрушение МХ [29], а также последующую гибель клетки. Важно отметить, что по существу Nrf2 выступает в качестве сенсора оксидативного стресса в клетке.…”