In oxidative damage prevention or removal, antioxidants play an important role [53,54]. By protecting the body from free radicals, antioxidants play an important role. There are two types of defense systems: enzymatic and non-enzymatic. Among the enzymes are SOD, glutathione peroxidase (GPx), and CAT, while the non-enzymatic vitamins are C, E, and selenium [55,56]. A weak antioxidant defense occurs when reactive oxygen species and free radical production increase greatly. By reducing antioxidant defenses, biological molecules and normal physiological and metabolic functions are damaged. The formation of reactive oxygen species occurs naturally in living organisms due to the release of free radicals. Normally, prooxidants and oxidants balance each other, but when the equilibrium is disturbed, harmful effects result. In cattle, oxidative stress occurs due to a decrease in antioxidant levels near the time of parturition [57,58].

Oxidative stress can weaken dairy cattle to several diseases and metabolic disorders during lactation. As a result, the physical condition and reproductive capability of dairy cows are affected [62]. During lactation, energy demands are increased, so this is the stressful stage with increased metabolic activities. The normal metabolism of the animals changes and stress is produced, thus metabolic disorder takes place. In addition, during the late period of pregnancy and the first stage of lactation, oxidative stress progresses in a negative energy balance (NEB) [47]. Dairy cows experience a drastic change in metabolism around parturition. Daily dry matter (DM) intake declines up to 30%, and at the same time before lactation, energy demand raises leading to NEB. This enhances metabolism harshly, resulting in a raised production of ROS and RNS. It is also well-known that dairy cows suffer from increased oxidative stress in late gestation and early lactation can be measured by a rise in thiobarbituric acid reactive substances (TBARS) including MDA [63]. The start of lactation is an important factor for free radicals production [64], mostly a negative energy balance developed in lactating animals that have starved conditions.

A high intensity of energy is consumed by the gravid uterus for the growth and development of the fetus. During late pregnancy, the glucose requirement for the gravid uterus increases and there is also a greater requirement for lactation, demanding major adjustments in the production of glucose and use in the maternal liver, adipose tissues, and skeletal muscles. The negative energy balance during lactation can raise lipolysis and diminish lipogenesis, causing the raised level of non-esterified fatty acids and β-hydroxybutyric concentration, which mobilized the fats and indicator of fatty acids mobilization [68,69,70]. An imbalance in hepatic carbohydrates occurs due to the mobilization of excessive fats and fat metabolism resulting in metabolic problems, such as ketosis and fatty liver syndrome. Economic losses can be caused by metabolic disorders in dairy farmers such as decreased milk production, treatment costs, decreased reproductive efficiency, and greater involuntary culling. Lactation stimulates stress because it is a physiological condition that adapts to metabolism in cows [14]. After calving, the body condition score loss is linked with an NEB [71]. In cows, NEB is produced by the mobilization of body reserves, because more nutrition is needed for milk synthesis. It is well known that to meet the nutritional demands of milk synthesis, dairy cows need to mobilize body reserves; awaiting nutrient intake covers the demand [71,72]. The study of Basoglu et al. [73] indicated that there was an increase in glucose VLDL, triglyceride levels before parturition, HDL levels, and cholesterol during late lactation in dairy cows. The dairy cows were tending to the fatty liver because of lower VLDL and glucose levels in early and late lactation and were inclined to hyperketonemia in early lactation because of lower insulin levels than in late lactation. Hagawane et al. [74] reported that in early and late lactating cows, blood glucose concentration was lower and significantly increased in dry cows. The downward trend of serum cholesterol was observed in dry pregnant cows as compared to lactating cows. The study of Piccione et al. [75] experimented on five healthy pregnant and lactating Holstein Friesian dairy cows. Samples of blood were collected at late gestation and early lactation during the 15, 35, and 105 days after parturition and at the end of lactation. Urea, total proteins, creatinine, albumin, total cholesterol, triglycerides, nonesterified fatty acid (NEFA), β-hydroxybutyrate, total and indirect bilirubin, calcium, phosphorus, and magnesium were determined on each sample. It was observed that the physiological phases have a significant effect on urea, creatinine, total proteins, total cholesterol, triglycerides, NEFA, β-hydroxybutyrate, calcium, and phosphorus. The study confirmed that a metabolic lactation period is more rational for the high-producing dairy cow. During the three situations such as late pregnancy, lactation, and disease, animals had undergone a negative energy status. High-yielding dairy cows during lactation undergo an NEB because energy is used for milk production and less feed intake; during the first four weeks of lactation, lipids uptake is increased by the liver thus the capacity of lipid oxidation results in a fatty liver or hepatic lipidosis. During the first stage of lactation in high yielding cows, lipid mobilization was observed, causing the liver lesion by fatty infiltration.

During metabolism, reactive oxygen species are produced, and their production and balance are controlled by enzymatic and non-enzymatic defense mechanisms [77]. Enzymatic antioxidants are SOD and CAT, while ascorbate, vitamin E, and β-carotene are non-enzymatic antioxidants. Due to elevated energy demand and increased oxygen necessity during lactation, oxidative stress is produced [78]. Lactation is a physiological action; any change in biochemical positions results in complications. Bhullar et al. [79] studied lipid peroxidation, glutathione peroxidase, and superoxide dismutase behavior, finding that they were firm with the plasma level of vitamin E and β-carotene during early, mid, and late pregnancy, early lactation, and the dry period.

On Holstein dairy cows, Sharma et al. [59] studied the stress due to oxidants and in turn antioxidant conditions during advanced gestation and early lactation. MDA was measured as a marker of lipid peroxidation and SOD, CAT, GSH, and GPx as antioxidants. During early lactation, the values of lipid peroxidation were significantly higher as compared to advanced gestation stages. In early lactation between MDA and CAT, a significant positive correlation was found. Blood glutathione (GSH) was significantly lower in early lactating cows than in the late pregnant stage. There was no significant negative correlation between lipid oxidation and all antioxidant enzymes. It is concluded that dairy cows have more oxidative stress and less antioxidant defense during early lactation than late pregnant cows.

The TAS scale has been used to determine the active balance between prooxidants and antioxidants. Oxidative stress is determined by the ratio of total peroxides to total antioxidant capacity. The serum TAS level was higher in the first week of lactation than in the cattle in pregnancy and late lactation. According to Castillo et al. [80], antioxidant activity diminishes with the passage of lactation. Castillo et al. [81] studied the values of lipid hydroperoxides and TAS in healthy cows and also studied their relationship with milk yield. The results indicated that there was a higher level of lipid hydroperoxides present in the group with a high milk yield than the other. This high oxidant compound is not accompanied by an increased level of defensive antioxidant substances. A TAS measurement gives balancing information about the metabolic status of parameters than parameters. Mousa and Galal [82] found that the concentration of TAS was significantly poorer before calving and the TAS concentration elevated eight weeks after calving. The decreased TAS rate before calving was synchronized with the deficiency of vitamins and minerals.

The PON1 is a calcium-dependent glycoprotein in nature that is linked with HDL [83]. PON1 acts as an enzyme that hydrolyzes organophosphorus. It has been recommended that increased oxidative stress might be associated with decreased serum PON1 activity, anti-inflammatory and antioxidative properties, and activities of PON1 give relief from physiological oxidative stress as well as contaminated environmental chemicals [84]. The liver is the site where the PON1 gene is expressed. After production, some of the PON1 residue is inside the hepatocytes and some of it is free in the blood where it is attached to HDL by association with apolipoprotein [85]. Hussein and Staufenbiel [86] studied the Cp action and copper (Cu) concentration in plasma and serum in dairy cows. In addition to this, a ceruloplasmin to Cu ratio was also observed. Serum Cu, plasma Cu, and plasma ceruloplasmin activities were increased in the fresh lactating stage. Serum ceruloplasmin showed no significant difference between fresh and early lactation. It was found that plasma Cu and plasma ceruloplasmin concentrations were increased, rather than serum Cu and Cp. Vitamin E is an antioxidant and hinders peroxidation, removes free oxygen radicals, and mixes up the break of peroxidation chain reactions by a holdback of reactive oxygen species. Near the parturition, vitamin E supplementation decreases the level of ALT, AST, and alkaline phosphatase (ALP); thus, it prevents oxidative stress by neutralizing reactive oxygen species during late pregnancy and early lactation, and the liver condition becomes better. The cows during lactation and mastitis have lowered vitamin C in milk and plasma [86]. Vitamin C scavenges the reactive oxygen species by a fast electron transfer and inhibiting lipid peroxidation, showing an important antioxidant defense next to oxidative damage. Cellular and non-cellular immunity can be increased by the antioxidant vitamins. Vitamin C has an inspiring effect on the phagocytic activity of leukocytes and the formation of antibodies. Vitamin C with the phagocytic cells uses free radicals and reactive oxygen species to destroy the pathogen. Thus, vitamin C defends the cells from oxidative damage [87].

Ruminant medicine is relatively new in terms of assessing oxidative status. There have actually been a number of studies in cattle, sheep, and goats, but they have mostly focused on the effects of diseases, such as mastitis, pneumonia, sepsis, acidosis, ketosis, enteritis, joint disease, and retained placentas [88,89,90]. Nowadays, peripartum metabolic diseases are becoming increasingly studied in dairy ruminants, while dairy cattle blood biochemical parameters are well-established as a means of analyzing metabolic profiles [67]. Nevertheless, metabolic profile tests can serve as an effective method of discovering which areas of dairy management and nutrition require more attention [91].

Free radical damage detection has emerged as an important complementary tool for evaluating metabolic status in recent years [92]. To combat free radical accumulation, the body has sufficient antioxidant capacity under normal physiological conditions, while ROS are produced in the body as a result of aerobic metabolic pathways. Maintaining homeostasis requires an equilibrium between ROS production and neutralization [93]. It is important to know that when domestic animals are in the productive phase, oxygen free radicals are produced [94]. There are a number of biomarkers that can be used to monitor oxidative stress, which result from increased exposure to or production of oxidants. Through TAC estimation, antioxidative systems are monitored for their efficacy against ROS. Antioxidants other than enzymatic antioxidants are found in serum, such as GSH, α-tocopherol, and β-carotene [95]. Taking into account the cumulative effects of all the antioxidants present in plasma, TAC is a useful, reliable, and sensitive indicator. Additionally, TAC can be used to assess the nutritional status of calves during transportation and for measuring stress. The measurement of TACs and the levels of MDA, as major components of total body antioxidants in dairy cows, are useful in identifying their relationship to lactational stages and the dry period [91].

The major portion of the total antioxidants in the body are plasma total thiols, which serve as a marker of oxidative protein damage. Thiol compounds have a high antioxidant capacity since the sulfur atom can easily accommodate electron loss [96]. There have been reports indicating that total thiol levels are low in various physiological and pathological conditions, such as diabetes mellitus, cardiovascular disorders, kidney disorders, and neurological disorders that are caused by excessive free radical production [97,98,99,100]. A primiparous cow, or a cow in the early stages of lactation, is more susceptible to infections and metabolic diseases than a multiparous cow [101,102]. For this reason, it is vital to assess the metabolic and oxidative markers in cows to detect at-risk cows, especially primiparous or early lactating cows.