Because oxidative stress is a process linked to several illnesses, antioxidants are essential for preserving our health. In this thorough investigation, we examine the antioxidants' mode of action and clarify the strength of natural sources.
Understanding Antioxidants
Antioxidants are substances that counteract dangerous chemicals referred to as free radicals. Unpaired electrons in unstable atoms or molecules are known as free radicals, and they try to find stability by grabbing electrons from neighbouring cells. Oxidative stress is the process that causes ageing and many health problems, including chronic illnesses.
Mechanism of Action
· Electron Donation: Free radicals get a large electron donation from antioxidants, which counteracts the detrimental effects of the radicals. The free radicals are stabilized by this electron donation, which stops them from harming cellular structures.
· Enzymatic Reactions: Certain antioxidants function as catalysts in these types of reactions, assisting in the disintegration of toxic materials and guaranteeing the elimination of any dangers to the integrity of cells.
· Metal-binding proteins are among the antioxidants that can chelate metals that can stimulate the production of free radicals. Antioxidants stop the start of oxidative stress by securing these metals.
· Control of Signaling Pathways: Signaling pathways connected to cellular reactions and inflammation are regulated by antioxidants. Antioxidants lower the danger of oxidative damage by balancing the cellular environment through the regulation of various mechanisms.
Natural Antioxidants
Vitamins
· Vitamin C is a powerful water-soluble antioxidant that may be found in bell peppers, citrus fruits, and strawberries. It promotes the renewal of other antioxidants and counteracts free radicals in bodily fluids.
· Vitamin E is a fat-soluble antioxidant that shields cell membranes from oxidative damage. It is found in large quantities in nuts, seeds, and vegetable oils.
Polyoxides
· Flavonoids: Found in tea, fruits, and vegetables, flavonoids have potent antioxidant qualities. They have anti-inflammatory and anti-cancer properties as well.
· Resveratrol: Resveratrol is a polyphenol that is present in red wine and grapes and is linked to several health advantages, such as heart protection and anti-ageing properties.
Polyphenols
· Carotene beta: Beta-carotene, which is abundant in sweet potatoes, carrots, and spinach, is transformed into vitamin A and functions as a potent antioxidant to boost the immune system and eyesight.
Minerals
· Selenium: Selenium is a trace element that is present in nuts, seeds, and seafood. It is crucial to produce antioxidant enzymes, which shield cells from harm.
· Q10 Coenzyme: Coenzyme Q10, an essential antioxidant involved in cell energy synthesis, is found in shellfish and organ meats.
Antioxidants defend the integrity of our cells by scavenging free radicals and averting oxidative damage. Adopting a diet high in naturally occurring antioxidants from diverse sources offers a comprehensive strategy to strengthen our body's defence systems. The incorporation of antioxidants into our lifestyle can help promote long-term health and prevent disease, even while research into their properties continues.
Melatonin
The body's natural hormone melatonin is essential for controlling the circadian rhythm, which is the cycle of wakefulness and sleep. It is secreted in a certain manner, rising in the evening as darkness falls and reaching its peak throughout the night to promote sound sleep. It is mostly produced by the pineal gland in the brain. The effect of this hormone spans a wide range of essential human health processes, even beyond the control of sleep. Melatonin has a wide range of other uses that support general health in addition to its part in the sleep cycle. Its antioxidant qualities lessen the harm that free radicals do to cells by preventing oxidative stress. This trait may potentially help prevent several age-related illnesses and ailments in addition to supporting cellular health.
Melatonin has been shown to play a role in immune system regulation in studies. It helps the body fight infections and lower the risk of some diseases by regulating the immune response. Furthermore, the anti-inflammatory qualities of melatonin contribute to immune system homeostasis, which is essential for general health. Moreover, the effects of melatonin extend to mental health and mood management. Because of its potential to interact with brain neurotransmitters, research indicates that it may have a role in the management of mood disorders such as anxiety and depression. Its importance goes beyond sleep management, as evidenced by its capacity to improve mood and reduce symptoms of seasonal affective disorder (SAD) [1].
Melatonin is primarily produced by the pineal gland; however, it is also present in tiny levels in some meals. Foods with trace amounts of melatonin include cereals, tomatoes, olives, cherries, and grapes. Because beer has a comparatively greater melatonin concentration than other drinks, it has drawn attention. However, there are general health concerns associated with alcohol intake, so caution is advised. Supplemental melatonin has gained popularity as a treatment for several sleep problems, including jet lag and insomnia. These pills, which are available over the counter, provide an option for those who experience sleep difficulties. They should be used cautiously, though, as suggested dosages usually start at 1 mg or less, and greater amounts can have negative effects including grogginess.
Even with all its advantages, using melatonin supplements needs caution. High dosages and prolonged usage may have adverse effects that include fracture risk and interference with the hormone's normal production. Furthermore, the efficiency of melatonin supplementation varies from person to person and is limited by its solubility in water, which influences absorption. Most melatonin supplements are made in labs and are used to treat sleep problems such as insomnia, delayed sleep-wake phase disorder, and jet lag. Different doses are recommended; the lowest doses should be no more than 1 mg. It is best to stay away from higher dosages (5 or 10 mg) due to potential adverse effects including grogginess.
Melatonin binds receptors (MT1 and MT2) in the hypothalamus suprachiasmatic nucleus (SCN) to regulate the circadian rhythm. This binding initiates downstream signaling cascades by phospholipase C activation, neurotransmitter release modification, and inhibiting cAMP signal transduction. Immunological response, mood control, sleep regulation, antioxidant activity, and fertility are among its physiological functions [2].
Melatonin and Its Antioxidant Role
The exceptional resistance of melatonin to macromolecular damage in a variety of experimental paradigms serves as a springboard for understanding its antioxidant effect. Numerous studies demonstrate how well melatonin functions as an endogenous defender by eliminating reactive oxygen intermediates and free radicals. In addition to directly scavenging free radicals, melatonin also affects the effectiveness of other antioxidants, especially those that protect the mitochondria from oxidative stress.
Melatonin's Antioxidant Activities
Examining melatonin's antioxidant properties in further detail reveals a variety of direct and indirect processes that establish it as a strong internal defence. The primary processes linked to melatonin include the scavenging of free radicals, activation of endogenous antioxidant enzymes, and augmentation of the effectiveness of other antioxidants. Melatonin's capacity to function through antioxidant pathways that are both receptor-independent and receptor-dependent demonstrates how versatile it is in addressing oxidative stress.
The special quality of melatonin is its capacity to cross blood-brain barriers and cell membranes with ease, shielding biomolecules from damage caused by free radicals. Melatonin detoxifies reactive oxygen and nitrogen species by acting as a direct scavenger, protecting against oxidative stress. Additionally, by increasing the activity of antioxidative defence mechanisms, it reduces oxidative stress indirectly [3].
Melatonin acts as a stimulant when there is prolonged oxidative stress, as free radicals can hinder or lessen the actions of antioxidant enzymes. Melatonin counteracts free radicals and increases the effectiveness of the antioxidant defence system by activating several antioxidative enzymes.
Melatonin's special qualities go beyond its immediate effects; its metabolites also function as antioxidants. By producing molecules that are radical scavengers and further limiting oxidative damage through many methods, this initiates an antioxidant cascade.
How it Combats Oxidative Stress and ROS
The capacity of melatonin to detoxify a wide range of free radicals and reactive oxygen intermediates demonstrates its effectiveness in combating reactive oxygen species (ROS) and oxidative stress. Melatonin's detoxifying properties encompass nitric oxide, singlet oxygen, peroxynitrite anions, and hydroxyl radicals [4].
Melatonin does more than only scavenge directly; it also plays an orchestra of antioxidative enzymes such as superoxide dismutase, glutathione reductase, glucose-6-phosphate dehydrogenase, and glutathione peroxidase. It also inhibits nitric oxide synthase, a prooxidative enzyme, concurrently. This double effect strengthens the cellular defence systems while simultaneously neutralizing dangerous radicals.
Melatonin offers shielding properties to nuclear DNA and membrane lipids against oxidative damage. Numerous animal models have demonstrated significant benefits in the treatment of oxidative stress, inflammation, and cellular death, indicating the therapeutic potential of melatonin [5].
Preclinical and Clinical Trials of Melatonin
Important insights have been gained from clinical research examining the effects of melatonin on neuroprotection and oxidative stress. Antioxidant biomarkers showed improvement and oxidative stress was significantly reduced in a comprehensive review and meta-analysis evaluating the effects of melatonin administration. Malondialdehyde (MDA), a lipid peroxidation marker, was the focus of the investigation. The results indicated that supplementing with melatonin may be a promising strategy for reducing molecular-level oxidative damage [6].
Melatonin showed significant protective benefits when ischemia/reperfusion (IR) damage occurred in the heart and brain. For example, Guerrero et al. studied gerbils using a bilateral common carotid clamp for 10 minutes to simulate ischemia. Neuroprotective effects were seen upon administration of melatonin at a dosage of 10 mg/kg body weight. Kilic and colleagues also performed studies with rat and mouse models, giving the subjects 90 and 120 minutes, respectively, for middle cerebral artery occlusion (MCAO). At 4 mg/kg body weight, melatonin showed promise in preventing the brain damage brought on by ischemia. All these investigations demonstrate that melatonin, at dosages of 4 to 10 mg/kg body weight, can protect against ischemia insult.
Research in the clinical domain has examined the effectiveness of melatonin under certain conditions. For instance, Fulia et al. administered a total of 80 mg of melatonin to neonates after a difficult vaginal delivery to examine the effects on the babies within the first six hours after birth. According to the study, melatonin administration may be helpful when hypoxic stress occurs, as it does with challenging births.
Moreover, research on both human patients and animal models has been done in the setting of cardiac IR damage. To study rat hearts ex vivo, Tan et al. clamped the left anterior descending artery for ten minutes. Melatonin was infused into the hearts at different dosages, demonstrating the protective benefits of the drug in a dose-dependent manner. Gogener et al. investigated the effect of melatonin on ischemia during abdominal aortic aneurysm repair in a clinical environment. Melatonin was given intravenously to the individuals for two hours at a level of 50 mg, and for three days following surgery, they were given an extra 10 mg daily. According to the study, melatonin administration could help reduce oxidative damage that occurs during vascular treatments [7].
In conclusion, melatonin's clinical trial results provide a thorough understanding of its effectiveness in a variety of contexts, from neonatal care and cardiovascular procedures to neuroprotection in ischemic circumstances. The different dosages employed in these trials show how much more research is required to determine the ideal amount and length of melatonin supplementation for clinical situations.
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