Protective Effect Of Creatine Research Articles

Creatine supplementation exacerbates ethanol-induced hepatic damage in mice

The aim of this study was to investigate the effects of creatine supplementation on early stages of ethanol-induced hepatic damage. Male Swiss mice were divided into three groups (n = 12/group): control (C), ethanol (E), and ethanol supplemented with creatine (EC). The control group received a diet containing 15.8% of total calories from proteins, 46.3% from carbohydrates, and 37.9% from lipids. The ethanol and ethanol and creatine groups received diets containing 15.8% of total calories from proteins, 16.2% from carbohydrates, and 34.5% from lipids; the remaining calories were obtained from the addition of 5% of 95% ethanol. Creatine (1%; weight/vol) was added to the diet of EC mice. After 14 and 28 d, six animals from each group were sacrificed, generating subdivisions in each group: C14 and C28, E14 and E28, EC14 and EC28. After sacrifice, the liver was removed, weighed, and prepared for histologic, biochemical, and molecular analysis, and blood was collected. Ethanol intake induced mild cell degeneration, liver damage, oxidative lesions, and inflammation. Surprisingly, ethanol intake combined with creatine exacerbated cell degeneration and fat accumulation, hepatic expression of genes related to ethanol metabolism, oxidative stress and inflammation, and promoted oxidative stress and elevated plasma alanine aminotransferase (P < 0.05). Creatine supplementation associated with ethanol is able to interfere in the alcohol metabolism and oxidative stress and to exacerbate ethanol-induced hepatic damage. These new findings are opposite to those observed in several studies where protective effects of creatine in a wide variety of injury models, including non-alcoholic fatty liver disease, were described.

24 - Protective effect of creatine against hyperglycemia induced oxidative damage in human erythrocytes

According to International Diabetes Federation data, in 2015 there were 415 million people suffering from diabetes worldwide and this number is expected to increase to 642 million in 2040. Studies have shown a strong relationship between hyperglycemia and oxidative stress (OS) that seems to play a crucial role in progression of diabetes mellitus (DM). In hyperglycemia associated oxidative stress conditions, reactive oxygen species (ROS) induced injury of erythrocytes results in abnormalities in their function, morphology and metabolism. Moreover, the ROS present in erythrocytes can be transferred to other cells, thus inducing and spreading tissue damage and inflammation. Hyperglycemia mediated erythrocyte redox state alterations might be a potential risk factor for the development of non-proliferative diabetic retinopathy in poorly controlled diabetic subjects. Antioxidants (AO) are now being looked upon as persuasive therapeutics to combat free radicals. AO are expected to prevent oxidative stress and diabetes-related complications by inhibiting the formation of and/or scavenging free radicals or by enhancing the capability of the endogenous antioxidant system. Creatine (Cr) is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Our previous work suggests that Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase erythrocyte lifespan. In this study, glucose cytoxicity is induced in erythrocytes and various biochemical parameters for assessing OS, ROS and nitrogen species were assayed in packed erythrocytes and cell lysates. Protection from oxidative damage to erythrocytes was analyzed using Cr and carnosine.

Magnetic resonance spectroscopy of regional brain metabolite markers in FALS mice and the effects of dietary creatine supplementation

We investigated the effects of disease progression on brain regional neurochemistry in a mutant mouse model of familial amyotrophic lateral sclerosis (FALS; the G93A model) using in vivo and in vitro magnetic resonance spectroscopy (MRS). There were numerous changes in the brain spectra that were brain region dependent. At early time points starting around 80 days of age there were increases in brain glutamate. At later time points there were more extensive changes including decreased N-acetyl aspartate and glutamate and increased glutamine, taurine and myo-inositol. The effects of the disease were most severe in spinal cord followed by medulla and then sensorimotor cortex. There were no changes noted in cerebellum as a control region. The effects of creatine supplementation in the diet (2%) were measured in wild-type and FALS animals in medulla, cerebellum and cortex. The increase in brain creatine was largest in cerebellum (25%) followed by medulla (11%) and then cortex (4%), reflecting the ordering of creatine kinase activity. There was a protective effect of creatine on N-acetyl aspartate loss in the medulla at late stages. Creatine supplementation had a positive effect on weight retention, leading to a 13% increase in weight between 120 and 130 days. MRS shows promise in monitoring multiple facets of neuroprotective strategies in ALS and ALS models.

Protective effect of creatine against RNA damage

It is well documented that damage to DNA could be very harmful for all cells and is the source of several consequences such as cancer development, apoptosis or genetic diseases. In contrast, RNA damage is a poorly examined field in biomedical research, despite its potential to affect cell physiology. For example, a significant loss of RNA integrity has been demonstrated in advanced human atherosclerotic plaques as compared with non-atherosclerotic mammary arteries, and oxidative RNA damage has been described in several neurodegenerative diseases including Alzheimer disease. In the present study, we investigated whether RNA damage could be related to the exposure of particular xenobiotics and then we studied the potential protective activity of creatine against RNA-damaging activity of a series of chemicals with different mechanisms of action [ethyl methanesulfonate (EMS), H 2O 2, doxorubicin, spermine NONOate, S-nitroso-N-acetylpenicillamine (SNAP)]. Since the protective effect against RNA damage can be mediated by different mechanisms, such as alterations of the rates of toxic agent absorption and uptake, trapping of electrophiles as well as free radicals, and protection of nucleophilic sites in RNA, we used two different treatment protocols (pre- and co-treatment) for understanding the mechanism of the inhibitory activity of creatine. We demonstrated that total RNA is susceptible to chemical attack by doxorubicin, H 2O 2, spermine and SNAP. Creatine significantly reduced the RNA-damaging activity of only two of the toxic tested agents (H 2O 2 and doxorubicin), while it lacked activity in counterstaining the RNA damage induced by the NO donors spermine and SNAP. Its inhibitory activity could be at least partially dependent on its capacity to directly scavenge free radicals and/or to maintain phosphocreatine store and ATP regeneration.

Differential effect of creatine on oxidatively-injured mitochondrial and nuclear DNA

Creatine is a naturally occurring compound obtained in humans from endogenous production and consumption through the diet. It is used as an ergogenic aid to improve exercise performance and increase fat-free mass. Lately, creatine’s positive therapeutic benefits in various oxidative stress-associated diseases have been reported in literature and, more recently, creatine has also been shown to exert direct antioxidant effects. Oxidatively-challenged DNA was analysed to show possible protective effects of creatine. Acellular and cellular studies were carried out. Acellular assays, performed using molecular approaches, showed that creatine protects circular and linear DNA from oxidative attacks. Nuclear and mitochondrial DNAs from oxidatively-injured human umbilical vein endothelial cells were analyzed. Creatine supplementation showed significant genoprotective activity on mitochondrial DNA. This evidence suggests that creatine may play an important role in mitochondrial genome stability in that it could normalize mitochondrial mutagenesis and its functional consequences. Thus, creatine supplementation could be used to prevent or ameliorate diseases related to mitochondrial DNA mutations, and possibly to delay aging.

The Creatine Kinase System in Human Skin: Protective Effects of Creatine Against Oxidative and UV Damage In Vitro and In Vivo

Cutaneous aging is characterized by a decline in cellular energy metabolism, which is mainly caused by detrimental changes in mitochondrial function. The processes involved seem to be predominantly mediated by free radicals known to be generated by exogenous noxes, e.g., solar ultraviolet (UV) radiation. Basically, skin cells try to compensate any loss of mitochondrial energetic capacity by extra-mitochondrial pathways such as glycolysis or the creatine kinase (CK) system. Recent studies reported the presence of cytosolic and mitochondrial isoenzymes of CK, as well as a creatine transporter in human skin. In this study, we analyzed the cutaneous CK system, focusing on those cellular stressors known to play an important role in the process of skin aging. According to our results, a stress-induced decline in mitochondrial energy supply in human epidermal cells correlated with a decrease in mitochondrial CK activity. In addition, we investigated the effects of creatine supplementation on human epidermal cells as a potential mechanism to reinforce the endogenous energy supply in skin. Exogenous creatine was taken up by keratinocytes and increased CK activity, mitochondrial function and protected against free oxygen radical stress. Finally, our new data clearly indicate that human skin cells that are energetically recharged with the naturally occurring energy precursor, creatine, are markedly protected against a variety of cellular stress conditions, like oxidative and UV damage in vitro and in vivo. This may have further implications in modulating processes, which are involved in premature skin aging and skin damage.

Creatine enhances survival of glutamate‐treated neuronal/glial cells, modulates Ras/NF‐κB signaling, and increases the generation of reactive oxygen species

The protective effects of creatine against glutamate cytotoxicity have been demonstrated in neuronal cells and animal models of neurodegenerative diseases. The mechanisms underlying creatine neuroprotection against glutamate-induced cell death are understood poorly. For the first time, we demonstrate a correlation between the protective effect of creatine and the modulation of Ras-mediated redox-dependent signaling pathways, which involve nuclear factor kappaB (NF-kappaB) and reactive oxygen species (ROS). In primary cerebrocortical cultures of mixed neurons and glia, creatine significantly reduced glutamate-induced cell death. The increase in cell survival was accompanied by increased generation of oxygen radicals and decreased levels of farnesylated Ras and IkappaB, an inhibitor of NF-kappaB. Non-farnesylated Ras and ROS-dependent activation of NF-kappaB have been shown to promote neuronal survival. Our data suggest that creatine may enhance survival signaling via activation of the Ras/NF-kappaB system. Possible mechanisms underlying the protective effect of creatine are discussed, including normalization of cellular GTP levels.