**2. Oxidative stress**

Living aerobic organisms have an intracellular environment in which important biological molecules are in equilibrium, and oxidative metabolism and redox homeostasis are in sync. In these organisms, oxidative phosphorylation is a vital step of metabolism [7].

This metabolic pathway uses the energy generated by NAD<sup>+</sup> oxy-reduction reactions in NADH and produces adenosine triphosphate (ATP) molecules capable of storing energy for immediate consumption [8]. As consequence, free radicals are produced naturally and continuously [9]. It is important to note that the mechanism of free radical generation can also occur in cell membranes and cytoplasm with the participation of transition metals such as iron and copper [10].

In the body, free radicals can act in a beneficial way during the immune response, destroying invading pathogens and modulating the excessive inflammatory response, however, their excess may cause deleterious effects to the organism. Normally, in healthy living organisms, there is a balance between the production of free radicals and antioxidant systems [11].

The imbalance between the production and the antioxidant defense capacity of the organism is called oxidative stress [12]. The cellular effects of this hostile environment depend on factors such as cell type, presence of surface receptors, mechanism of transduction and levels of antioxidants [7]. But it is known that prolonged exposure to oxidative stress can damage cellular components (proteins, lipids and DNA) [13], contribute to cellular aging [14], and play an important role in the pathogenesis of cancer, atherosclerosis, Parkinson, Alzheimer's and various chronic diseases such as diabetes mellitus and its complications [15–20].

prevalence of obesity and sedentary lifestyle [1]. It is estimated that currently about 415 million individuals are diagnosed with DM worldwide and it is predicted that by 2040 these

Although the survival of these patients has increased in recent decades, it is known that the morbidity resulting from complications affecting the small blood vessels (microvascular) or large (macrovascular) arteries is very significant. These complications may occur as consequence of hyperglycemia that favors inadequate cellular metabolism and excessive production of reactive oxygen species (ROS). The etiopathogenesis of DM is not fully elucidated, but it is suggested that genetic and environmental factors are involved in this metabolic disorder and, in this sense, oxidative stress becomes one of the important pathways for this understanding [3]. Human cells produce many antioxidants in attempt to protect cells against damage caused by toxins from the environment. The main endogenous antioxidant defense is provided by glutathione (GSH). GSH is a linear tripeptide that arouses scientific interest because it performs multiple functions via glutathione S-transferase (GST). GSTs are one of the most important groups of phase II enzymes. It is reported that these enzymes are induced, as a protective mechanism (detoxification), under conditions of oxidative stress. GST polymorphisms were associated with increased or decreased susceptibility of various diseases, such as cancer, car-

Some important members of the GST family stand out for having different polymorphisms between these GST mu 1 (GST M1) and GST theta 1 (GST T1) and GST Pi 1 (GSTP 1). It is reported that these GSTs subtypes are involved in the development of DM and its complications [5], so it is important to understand the impact of these oxidative changes and the pos-

Living aerobic organisms have an intracellular environment in which important biological molecules are in equilibrium, and oxidative metabolism and redox homeostasis are in sync.

NADH and produces adenosine triphosphate (ATP) molecules capable of storing energy for immediate consumption [8]. As consequence, free radicals are produced naturally and continuously [9]. It is important to note that the mechanism of free radical generation can also occur in cell membranes and cytoplasm with the participation of transition metals such as

In the body, free radicals can act in a beneficial way during the immune response, destroying invading pathogens and modulating the excessive inflammatory response, however, their excess may cause deleterious effects to the organism. Normally, in healthy living organisms, there is a balance between the production of free radicals and antioxidant systems [11].

oxy-reduction reactions in

In these organisms, oxidative phosphorylation is a vital step of metabolism [7].

This metabolic pathway uses the energy generated by NAD<sup>+</sup>

diac diseases, about everything diabetes and yours complications [4].

sible effects of genetic polymorphisms of GSTs in diabetic patients [6].

**2. Oxidative stress**

iron and copper [10].

records will reach the range of 672 million [2].

48 Glutathione in Health and Disease
