# Balance of Antioxidants vs. Oxidants in Perinatal Asphyxia
## 3 Pathophysiology
### Biological Antioxidant Systems  
Oxidative stress represents a metabolic imbalance caused by an excess of free radical production or a reduced capacity of the antioxidant defense system (ADS) [3]. While free radicals are necessary for cell communication and the proper operation of biochemical pathways, an extreme imbalance of the ADS and free radicals can damage tissues and lead to acute or chronic illnesses [17]. The ADS is developed later in pregnancy to prepare the fetus for oxygenation after birth and encompasses both enzymatic and non-enzymatic components. Antioxidant enzymes neutralize reactive species by undergoing chemical reactions. Non-enzymatic antioxidant systems consist of proteins that sequester metals (including ferritin, transferrin, and ceruloplasmin), vitamins that prevent the oxidation of lipids (like A, C, D, and E), and small molecules that diminish reactive species. Sufficient levels of vitamin A in the tissues could provide a defense against infections and the harmful effects of oxygen free radicals [18]. A previous study found significantly lower levels of vitamin A in neonates with reduced antioxidant defenses, as indicated by their increased need for delivery room resuscitation compared to controls [18]. In another study, low vitamin A levels during the first month of birth were found to greatly increase the likelihood of developing long-term respiratory impairment [19]. The antioxidant characteristics of vitamin C include the production of ascorbyl radicals, a terminal reactive oxygen species (ROS) with a relatively minimal harmful effect on biological systems. Although vitamin C is mainly considered an antioxidant, under specific circumstances, vitamin C may show prooxidant qualities in the presence of free (unbound) redox metals, such as iron or copper [20]. Numerous antioxidant processes are linked to vitamin D; when the condition of vitamin D and oxidation was assessed in neonates with NE, vitamin D levels were found to be lower than normal [21]. Additionally, the administration of vitamin D significantly reduced the malondialdehyde (MDA) content generated by hypoxia/ischemia and elevated glutathione (GSH) and SOD (superoxide dismutase) activity, both of which were suppressed by hypoxia/ischemia. Among numerous mechanisms of cellular injury that have been linked to the creation of ROS [22], it has been shown that calcitriol, an active form of vitamin D, suppresses ROS formation by interfering with the hydrogen peroxide pathway [23]. Vitamin E protects cellular membranes from ROS-caused lipid peroxidation, with the hydroxyl group on its six-membered ring situated outside of the membrane and scavenging ROS in the aqueous environment. Furthermore, there has been great interest in the content of trace elements and their potential role as key regulators of antioxidant defense and oxidative stress. Copper is a cofactor in numerous detoxification enzymes and proteins, including SODs, ceruloplasmin, and copper-thioneineine [24]. In preterm newborns, a decrease in SOD activity was linked to low copper levels [25]. Regarding ferrum, studies have shown that children with ferrum-deficiency anemia exhibit a decrease in antioxidant activities, such as that of catalase [26]. Zinc is essential for cell differentiation, metabolism, and growth, while promoting antioxidant enzyme activities like Zinc-SOD and Zinc-thioneine, hormone structures, and brain development [24]. Moreover, the importance of selenium for the best possible operation of the body's natural antioxidant defense mechanisms is becoming more widely recognized [27]. The \"selenoenzymes\" glutathione peroxididases (GPx), thioredoxin reductases, and selenoprotein P are produced only when selenium is present [28; 29]. Through selenoproteins, selenium is linked to the regulation of ROS levels and redox balance in nearly every tissue. Due to its significant antioxidant effect, low selenium levels have been linked to impaired oxidative system defenses [30].