Maintaining the structural and functional integrity of the β-pancreatic cells is a priority. Oxidative stress and inflammation have been shown to be disturbing factors of this balance (Saeedi Borujeni et al., 2019; Gorasia et al., 2015). The consequences are the disruption of immune tolerance following crosstalk between immune cells and β-cells. The main causes seem to be the alteration of signal transduction, enzyme activity, gene expression or ion channels, in parallel with antigen presentation and induction of apoptosis (Piganelli et al., 2021). Active or passive smoking represents an additional risk to those stated previously, synergistically with obesity. Nicotinamide has been shown to be beneficial in disease prophylaxis in high-risk individuals and stimulation of residual insulin secretion in newly diagnosed patients. Similarly, beneficial effects were also recorded in the case of N-acetylcysteine administration or the correlation of insulin dose with carbohydrate intake (Ludvigsson, 1993; Tong et al., 2020; Kostopoulou et al., 2020). At the same time, Lee J et al. posit that multiple cellular processes encountered in pancreatic dynamics are rhythmic and subject to circadian regulation (Lee et al., 2018).

Interleukin 6 (IL-6) has been intensively studied regarding its role in the specific oxidative dynamics of diabetes. It is certified that IL-6 represents the crossroads between autophagy and the antioxidant response. Although it is a pro-inflammatory cytokine, IL-6 seems to have a protective role in the pathogenesis of diabetes. The decrease in its signaling in β cells increases their susceptibility to oxidative damage. In parallel, IL-6 reduces reactive oxygen species and mitochondrial activity, stimulating mitophagy (Marasco et al., 2018). Recent studies confirm the correlation between the level of IL-6 and the complications of diabetes, both in murine models and among young patients (Karahmet et al., 2021; Robinson et al., 2020). Reis JS. et al. argue that the functional changes involved in the complications of diabetes may begin as early as the first years of diagnosis. Consequently, IL-6 is a key pawn in adaptation to stress, marking new research directions regarding targeted therapies (Rajendran et al., 2020; Reis et al., 2012).

Retinopathy is classically defined as a complication of diabetes that structurally and functionally affects the posterior eye pole, with a frequency of approximately 15% since the time of diagnosis (Rodríguez et al., 2019). The physiopathological center of the disease is represented by ischemic tissue damage, later doubled by compensatory vascular neoformation (non-proliferative stage and proliferative stage) (Rivera et al., 2017). The mechanisms implicated in ocular tissue damage are atmospheric oxygen, hyperglycemia (through advanced glycosylation products, peroxisome proliferator-activated receptor γ disruption, epigenetic changes), inflammation, environmental chemicals, and free radical-catalyzed peroxidation of long-chain polyunsaturated acids. This results in toxic metabolites. Furthermore, oxidative stress is also involved in affecting the reendothelialization capacity (Guzman et al., 2017; Calderon et al., 2017; Gui et al., 2020). Wert KJ. et al. notes the involvement of superoxide dismutase-3 in vitro-retinal pathogenesis. This enzyme proved to be well represented in the vitreous body (Wert et al., 2018). Laser phototherapy, the administration of anti-vascular endothelial growth factor (VEGF) agents or vitrectomy are established therapeutic methods. Among the beneficial antioxidant substrates, we note the α lipoic acid, taurodeoxycholic acid, apocynin, polyphenols and vitamins (vitamin E, C, B1) (Rodríguez et al., 2019).

Oxidative stress can therefore precipitate the abnormalities induced by hyperglycemia and inflammation, mainly through the interaction with the polyol, hexosamine, angiotensin II pathways, the hyperactivation of protein kinase C isoforms (PKC) and the accumulation of advanced glycation end products (AGEs) (Wu MY. et al., 2018; Kang and Yang, 2020). In addition to these, epigenetic changes, DNA methylation and the abnormal activity of nuclear factors (e.g., strongly activated nuclear factor κB -NF-κB-), doubled by the attenuation of NRF2 activity, have been shown to be involved in the accumulation of free radicals (Duraisamy et al., 2018). All these changes form a vicious circle, leading over time to mitochondrial, microvascular dysfunction and apoptosis. Further, ischemia and local inflammation occur, which stimulate neovascularization, macular edema and neurodysfunction (Kowluru, 2023). In conclusion, oxidative stress represents an important pillar in the pathogenesis of diabetic retinopathy. In this sense, an individualized antioxidant therapy of patients can be obtained, centered on optical coherence tomography as a screening method. The technique seems to be able to evaluate the oxidative stress of the subretinal space. To this must be added the obtaining of an adequate glycemic control.

From a pharmacological point of view, the substances used in the management of diabetic retinopathy are diphenyleneiodonium, apocynin, triamcinolone acetonide, dexamethasone sodium phosphate, fluocinolone acetonide, statins, fenofibrate, or glucagon-like peptide 1 receptor agonists (GLP 1) (Rodríguez et al., 2019; Berkowitz, 2020). To these are added the previously mentioned antioxidant substances, doubled by microelements (zinc, copper, selenium, manganese), sirtuin pathway modulators (antagomiR, resveratrol, glycyrrhizin, melatonin), N-acetyl cysteine, benfotiamine, nicanartine, capsaicin, β-carotene, taurine, lutein, caffeic acid phenethyl ester, cannabidiol, 8-hydroxy-N, N-dipropyl-2-aminotetralin and green tea (Kang and Yang, 2020; Berkowitz, 2020; Li et al., 2017; Nebbioso et al., 2022; Liu et al., 2022; Tu et al., 2021).

Diabetic nephropathy is another microvascular complication encountered in the evolution of diabetes with a frequency of up to 40% of cases (Darenskaya et al., 2023). The defining histological features are glomerular hypertrophy, basement membrane thickening, mesangial expansion, tubular atrophy, interstitial fibrosis, and arterial thickening (Darenskaya et al., 2023; Kashihara et al., 2010; Sagoo and Gnudi, 2018). Mamilly L. et al. underlines the positive correlation between the development of nephropathy and glycemic variability (Mamilly et al., 2021). However, the pathogenesis of renal damage in diabetic nephropathy is multiple and far from being completely elucidated. Among the newly introduced therapeutic targets in the field of research, we delimit oxidative stress which, together with hyperglycemia, forms a vicious cycle with a strong impact on metabolic homeostasis and organic functionality (Arora and Singh, 2014; Artenie et al., 2004). Several molecules compete in the modulation of oxidative stress, among which we note NADPH oxidase (subtypes 1, 2 and 4), xanthine oxidase, lipoxygenase, cytochrome P450, AGEs, disturbances of the polyol pathway, uncoupled nitric oxide synthase or the respiratory chain mitochondria. The goal is to reduce the risk of progression of diabetic nephropathy to chronic renal failure (Goycheva et al., 2023; Østergaard et al., 2020; Yamagishi and Matsui, 2010). It is known that chronic renal failure is a pathology accompanied by systemic dysbiosis, thus potentiating the occurrence of other diseases through the intestine-target organ axes. Among the pathologies whose list of precipitating factors includes dysbiosis, we mention inflammatory conditions, autoimmunity or atopy. At the same time, it is known about patients in the final stage of renal damage that they have a much-reduced capacity to compensate for the negative effects of oxidative stress (Pantazi et al., 2023; Mocanu et al., 2023; Lupu et al., 2023b; Lupu et al., 2024a; Lupu et al., 2024b; Lupu et al., 2023c; Lupu et al., 2023d; Ioniuc et al., 2024; Lupu et al., 2024c). The mechanism involved in renal decline is the increase in the expression of extracellular matrix genes following the stimulation of protein kinase C, mitogen-activated protein kinases and various cytokines and transcription factors by reactive oxygen species represented in excess. Added to this is the overexpression of the renin-angiotensin system (Kashihara et al., 2010; Sagoo and Gnudi, 2018).

The main organelles damaged by oxidative stress were found to be peroxisomes. Known for their multiple metabolic roles, they undergo functional changes depending on systemic conditions predisposing to the increase of free radicals. In this sense, studies on murine models have shown the benefit of supplementing with antioxidants in restoring peroxisomal balance and mitigating diabetic nephropathy (Dhaunsi and Bitar, 2004). Phytochemical substances (e.g., dietary antioxidants, Chinese medicinal plants, vitamins, trace elements - selenium, zinc -, catechins, coenzyme Q10, omega-3 fatty acids, resveratrol, curcumin, quercetin, soy, dioscin, α-lipoic or phenolic acid) are known for its beneficial effect on renal function and alleviation of oxidative stress (Hernandez et al., 2022; Gerardo Yanowsky-Escatell et al., 2020; Hu et al., 2022; Chen M. et al., 2023; Zhong et al., 2022). To these are added kelch-like ECH-associated protein 1, NRF2, lipoxin and glutathione peroxidase-1 representing antioxidant mechanisms whose integrity depends on the evolution of diabetic nephropathy (Darenskaya et al., 2023; Østergaard et al., 2020). Besides these, the functionality of metabolic pathways mediated by AMP-activated protein kinase (AMPK)/Sirtuin-1 (Sirt1), the transcription factor SIRT1-forkhead O (FOXO), Sirt1 and NF-κB can be influenced by oxidative stress (Jin et al., 2023). In addition, Peters V. et al. highlight the possible inclusion of carnosine (β-alanyl-L-histidine) among modern therapeutic approaches. The interest in this is partly due to its anti-inflammatory and antioxidant properties. The disadvantages of human administration reside in the reduced halving period (Peters et al., 2020).

Among the effective pharmacological therapies, we mainly discuss antidiabetics such as GLP1, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose transport protein 2 (SGLT2) and insulin. Adjuvants include Rapamycin, Ruboxistaurin, Pentoxifylline, the Ursolic Acid - Empagliflozin combination, aspirin and cyclooxygenase-2 (COX-2) inhibitors, 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase inhibitors, adiponectin and the monocyte chemoattractant protein inhibitor. 1 and 2 (MCP-1 and MCP-2) (Østergaard et al., 2020; Mima, 2013; Wu et al., 2021). To these is added the achievement of good glycemic control, the adequate maintenance of blood pressure and lipid profile, together with the approach of a healthy lifestyle (Singh et al., 2011).

It manifests itself through intense pain and a decrease in the quality of life, reported in up to 1/3 of patients with diabetes, regardless of the associated neurological deficits (Pang et al., 2020). The physiopathological mechanisms directly involved are axonal degeneration occurring in cells with a reduced capacity to modulate their carbohydrate intake following chronic hyperglycemia and the excess production of reactive species (Ye et al., 2022). The indirect means that disrupt the neuronal balance are increased inflammation and mitochondrial dysfunction (Fernyhough and McGavock, 2014). In a secondary plan, we discuss the effect of genetic polymorphism in the pathogenesis of complications associated with diabetes (Babizhayev et al., 2015). It is also noted that pain processing in the central nervous system is compromised in diabetic neuropathy. Depending on the degree of damage and duration of symptoms, neuropathy can be divided into diffuse and focal (less frequent and often self-limited). The most common form is distal symmetrical polyneuropathy of the lower and upper extremities (Dewanjee et al., 2018; Sztanek et al., 2016).

There is an increased risk that patients with polyneuropathy will develop cognitive impairment (e.g., dementia). At the same time, maternal diabetes may predispose to fetal neurodevelopmental defects. Therefore, close follow-up of patients is essential. To facilitate this, Etienne I. et al. discuss the utility of correlating low malondialdehyde levels with the coexistence of diabetes mellitus and diabetic polyneuropathy (Etienne et al., 2019; Jin et al., 2016).

In combating oxidative stress and its effects on the quality of life of patients with diabetic neuropathy are essential substances such as α-lipoic acid, vitamins (A, C and E), acetyl L-carnitine, taurine, melatonin, quercetin and N–acetylcysteine (Pang et al., 2020; Zhang et al., 2021). Methylcobalamin is added to these, a substance that competes with α-lipoic acid in terms of therapeutic efficiency in reducing the sensation of numbness and paresthesia. In contrast, α-lipoic acid is recommended when the predominant complaints are burning and pain (Han et al., 2018). If in diabetic nephropathy Ruboxistaurin (specific inhibitor of protein kinase C) has proven therapeutic efficiency, in neuropathy aldose reductase inhibitors (Epalrestat, Ranirestat) and anti-AGE agents (Benfotiamine) have rather demonstrated a therapeutic effect. An effective solution appears to be the double association of phosphodiesterase inhibitors (Rolipram and/or Pentoxifylline), aiming both at reducing oxidative stress and the level of inflammatory factors (Dastgheib et al., 2022). For adjuvant purposes, it is possible to use antiepileptic drugs (Pregabalin, Gabapentin), antidepressants (Duloxetine), opioid analgesics (Tramadol) or non-steroidal anti-inflammatory drugs (Dewanjee et al., 2018). Dexmedetomidine (anxiolytic, analgesic and sedative derived from imidazole) and Hesperidin are also an approach considered promising in the future (Lin et al., 2023; Syed et al., 2023).

Future strategies focus on the use of hydrogen therapy in alleviating diabetic symptoms and reducing the morbidity caused by it. The benefits of its administration include reduction of blood glucose, improvement of motor nerve conduction velocity, mitigation of oxidative stress (reduction of malondialdehyde, reactive oxygen species and 8-hydroxy-2-deoxyguanosine), partial restoration of superoxide dismutase activities and regulation of NRF2 expression (Han et al., 2023).

The two entities that are the subject of this subchapter (diabetes and cardiocirculatory manifestations) have a common pathogenic background represented by low-grade chronic inflammation (Hariharan et al., 2022). Added to this is the impact of oxidative stress on cardiovascular and metabolic balance. Its main determinants appear to be obesity, diabetes, smoking and pollution (Hertiš Petek et al., 2022; Cojocaru et al., 2023; Niemann et al., 2017; Lupu A. et al., 2024). The role of intervention in modulating these variables is vital, its absence being accompanied by medium- and long-term consequences on the health of patients (for example, chronic inflammation in childhood increases the risk of atherosclerosis and cerebrovascular diseases). Also, there is evidence of the direct correlation between the level of oxidative stress, the relative risk of cardiovascular damage and mortality and the value of glycosylated hemoglobin (HbA1c), respectively the period of manifestation of diabetes. The link is objectified by the escalation of endothelial, inflammatory and pro-coagulant biomarker values among patients with poorly controlled diabetes (Hertiš Petek et al., 2022; Zhao et al., 2021; Domingueti et al., 2016; Seckin et al., 2006; Letunica et al., 2021). For an easier presentation of the subject, in what follows, we will subdivide the discussion into two directions of interest, namely, cardiac and vascular damage.

Vitamin A represents a group of fat-soluble retinoids, with implications on growth, differentiation and cell signaling (through the intranuclear receptor), gene regulation, muscle integrity, resistance to infections and immunological balance. The optimal dose is between 200 and 500 μg/day (Martini et al., 2020; Iqbal and Naseem, 2015). Vitamin A is found in increased quantities in the following foods: liver and liver products, kidney and offal, oily fish and fish liver oils, eggs, carrots, red peppers, spinach, broccoli and tomatoes (Webster-Gandy et al., 2006).

Vitamin C (ascorbic acid) is a water-soluble vitamin with a role in the integrity of the connective tissue, the modulation of systemic enzymatic reactions and the functions of the central nervous system. At the same time, vitamin C increases nitric oxide production in endothelial cells by stabilizing the nitric oxide synthase cofactor, thereby neutralizing reactive oxygen species. Appropriate daily doses are between 35 and 75 mg (Johansen et al., 2005; Martini et al., 2020). Foods rich in vitamin C found in the daily diet are kiwi fruit, citrus fruit (oranges, lemons, satsumas, clementines, etc.), black currants, guava, mango, papaya, pepper, brussels sprouts, broccoli and sweet potato (Webster-Gandy et al., 2006).

Vitamin E is a fat-soluble vitamin (along with vitamin A), subdivided into 8 isoforms, of which the most active and intensively studied in the human species is α-tocopherol. Tocopherol reacts with the hydroxyl radical, neutralizing it by forming a stabilized phenolic radical that will later be reduced to the phenolic ring (Zatalia and Sanusi, 2013). Giannini C. et al. demonstrate through the cross-over, double-blind study, over a period of 12 months, the benefit brought by supplementation with high doses of vitamin E (1,200 mg/day) on the reduction of pro-oxidative markers and the improvement of antioxidant defense. However, supplementation could not restore the damage already done (Giannini et al., 2007). Later, Dotan Y. et al. disapprove the supplementation without discrimination, basing his statement on the results of recent meta-analyses that validate its correlation with increased mortality. The authors emphasize the need to outline some indications for its use in order to reduce the consequences, among them are the people known to be subject to oxidative stress (Dotan et al., 2009). Among the food’s rich in vitamin E, recommended for daily consumption, we note wheat germ oil, almonds, sunflower seeds and oil, safflower oil, hazelnuts, peanuts, peanut butter and corn oil (Webster-Gandy et al., 2006).

The B vitamin complex is made up of thiamin (B1), riboflavin (vitamin B2), niacin (B3), pantothenic acid (B5), pyridoxine (B6), biotin (B7), folic acid (B9) and cobalamin (B12). These vitamins are water-soluble and target various physiopathogenic stages during oxidative stress (Martini et al., 2020; Webster-Gandy et al., 2006). B1 plays an essential role in the oxidative decarboxylation of multienzyme branched chain ketoacid dehydrogenase complexes of the citric acid cycle. At the same time, its level can mark the neuroprotection/neurodegeneration balance (Depeint et al., 2006; Gibson and Zhang, 2002). B2 is a necessary cofactor for the flavoenzymes of the respiratory chain, glutathione reductase, simultaneously mitigating oxidative reperfusion injuries and lipid peroxidation (Depeint et al., 2006; Ashoori and Saedisomeolia, 2014). In parallel, B3 is a cofactor in the synthesis of NADH, being important in the economy of the amount of protons required for oxidative phosphorylation (Depeint et al., 2006). B5 is a necessary substrate for the formation of coenzyme A. It is also involved in the dynamics of the alpha-ketoglutarate and pyruvate dehydrogenase complexes, but also in the oxidation of fatty acids (Depeint et al., 2006). B6 is mentioned as an enzyme cofactor in more than 140 chemical reactions. Distinct from this, B6 has properties of reactive oxygen species scavenger, being a strong antioxidant, metal chelator and carbonyl cleaner (Depeint et al., 2006; Mooney and Hellmann, 2010; Wondrak and Jacobson, 2012). B7 is required for gluconeogenesis and fatty acid oxidation (Iqbal and Naseem, 2015). B9, together with its metabolite (5-methyltetrahydrofolate) regulates the bioavailability of nitric oxide by increasing the production and coupling of endothelial nitric oxide synthase. Thus, it interferes directly with the cleaning of superoxide radicals (Stanhewicz and Kenney, 2017). Mainly, B12 has the role of stabilizing DNA, being a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase. At the same time, it is involved in cleaning free radicals and reducing oxidative stress (Depeint et al., 2006; Halczuk et al., 2023).

In conclusion, the B vitamin complex is involved in ameliorating the toxicity induced by oxidative stress. However, supplementation must be judicious, Kandel R. et al. noting that prolonged exposure to large amounts of folic acid can induce acute renal cytotoxicity and fibrotic changes. The risk was reduced by the addition of N-acetylcysteine. Therefore, the use of vitamins from the B complex must be judicious. Of these, we note as a dosage standard a requirement of 0.7–2 μg/day of vitamin B12, respectively 110–320 μg/day of folic acid (Kandel and Singh, 2022). Food sources rich in these are eggs, milk and milk products (e.g., cheese, yoghurt), liver, kidney, yeast extracts, fortified breakfast cereals, bananas, yeast, offal, peanuts, nuts, brussels sprouts, cabbage, kale, spinach, broccoli, cauliflower, chickpeas, green beans, icebergs, lettuce, beans, peas, spring greens, potatoes, brown rice, whole grain pasta, beef, pork, chicken, salmon, game, wheat flour and maize flour (Webster-Gandy et al., 2006).

Their main role in the systemic oxidative economy is attributed to their function as enzyme cofactors. Taking zinc as an example, it modulates metallothionein activity. Protein rich in cysteine, metallothionein has the property of binding metals, modulating cellular and immune homeostasis. Thus, it exerts its antioxidant, antiapoptotic, detoxifying and anti-inflammatory effects. Intervenes in the signaling pathways induced by stress, thereby imprinting the evolutionary course of diabetes (Park et al., 2018). Foods recommended in the daily diet to avoid microelement deficiencies are lamb, green vegetables, pulses, leafy and root vegetables, crabs and shellfish, beef, offal, whole grains, pork, fish, poultry, milk and milk products, eggs, nuts (Webster-Gandy et al., 2006).

It represents one of the major redox buffering systems. Its roles are bidirectional, acting both as a direct scavenger and as a cofactor for the enzyme glutathione peroxidase (Johansen et al., 2005). In order to supplement it, the current literature notes that the oral intake of preformed glutathione, the supplementation of other constituents that regulate its level (e.g., N-acetylcysteine, omega 3, riboflavin, vitamin C, vitamin E, α-lipoic acid, selenium) are also possible options. and the increased intake of protein foods, in parallel with the optimal maintenance of gastric hydrochloric acid and pancreatic enzymes necessary for digestion. Food sources rich in glutathione are asparagus, broccoli, green beans, lemon, grapefruit, mango, avocado, banana, orange, papaya, parsley, potato, red pepper, bell pepper, spinach, strawberry, tomato, cucumber, carrot, yellow squash, cauliflower (Minich and Brown, 2019).

These are compounds found mainly in foods of vegetable origin, which have antioxidants, anti-inflammatory and immunomodulatory properties. It exerts its antidiabetic role mainly by reducing the intestinal absorption of glucose, increasing pancreatic insulin secretion, modulating the intestinal microbiota and its metabolites. Depending on the chemical structure, polyphenols are divided into four groups, respectively flavonoids, stilbenes, phenolic acids and lignans. The number of phenolic units and their combination leads to different physical, chemical and biological properties. A representative model is perhaps the antithesis of flavonoids (e.g., Quercetin) - stilbenes (e.g., Resveratrol, Curcumin) (Jin et al., 2023). The main sources of dietary flavonoids are pomelo, blueberries, roselles, oranges, grapefruit, lemons and limes (Sapian et al., 2021).

Quercetin is a bioflavonoid compound (flavonol), composed of 15 carbon atoms joined in the form of two benzene rings and a heterocycle. It has demonstrated effects in the suppression of cell proliferation, inflammation and oxidative stress, in part by regulating glycolipid metabolism and improving the bioavailability of nitric oxide (Zhang et al., 2021; Sapian et al., 2021). At the molecular level, it activates the NRF2/HO-1 pathway, suppresses the AGE-RAGE pathway, improves the expression of SOD, GPx and CAT, increases the content of high-density lipoproteins, simultaneously reducing the expression of triglycerides, low-density lipoproteins and the expression of inflammatory molecules (Jin et al., 2023). Renal, one of the mechanisms of action, according to Wan H. et al., is the miR-485-5p/yes-associated protein (YAP1) pathway. YAP1 is a multipotent protein, involved in various processes such as osteoblast differentiation, tumor biology and diabetes complications (e.g., it promotes kidney damage). Its modulation favors the improvement of interstitial fibrogenesis (Wan et al., 2022). Its effects are not limited to the nephrotic component, the consumption of flavonol stopping retinal degeneration, offering cardio and neuroprotection by controlling apoptosis, inflammation, neurodegeneration and cardiac remodeling that occur following oxidative stress. In conclusion, it is noted that the optimal intake of quercetin (90–150 mg/kg/day, for 2–4 months) improves renal function, increases the formation of nephrin and podocin, decreases desmin, improves the deletion of podocytes and improves renal histology. Foods rich in quercetin are onions, cabbage, lettuce, tomatoes, grapes, apples and berries (Jubaidi et al., 2021; Ola et al., 2018).

Resveratrol has a similar action to quercetin, but a different chemical structure, resveratrol activates antioxidant enzymes and decreases the secretion of superoxide anion, hydroxyl radical, and inflammatory cytokines by modulating the NRF2/kelch-like ECH-associated protein 1 signaling pathway and AMPK expression. Additionally, it modulates Cyto C transport activity, thus delaying the progression of podocyte and tubular apoptosis (Jin et al., 2023). Curcumin is an extract of medicinal plants with significant antioxidant properties. It can reduce hypoxia and prevent angiogenesis by modulating hypoxia-inducible factor 1. It is noted that curcumin supplementation can inhibit VEGF expression (Li et al., 2017).

This is an endogenous, fat-soluble compound, considered to act on the electron balance of complex II in the mitochondrial transport chain. It is noted that, in high concentrations, it helps the clearance of free radicals, thereby improving endothelial function (Johansen et al., 2005). Food sources of coenzyme Q10 are mainly meat, fish, nuts and some oils. To these, dairy products, vegetables, fruits and cereals are added, in a significantly lower quantity. It is also worth mentioning the variability of the concentration of coenzyme Q10 in foods depending on the geographical area from which they come (Pravst et al., 2010).

It is considered one of the miracle molecules at the moment, performing numerous roles such as cleaning free radical species, regulating insulin metabolism, supporting the immune system, slowing down aging, counteracting insomnia, systemic inflammation, malignancies, periodontal pathologies, neuroprotection, mood balancing, sexual maturation and body temperature control. Looking specifically at the role of melatonin in counteracting systemic oxidative stress, we know that it plays the role of scavenger of excessive free radicals, more potent compared to nicotinamide adenine dinucleotide phosphate (NADPH), vitamin C and vitamin E. It also increases the efficiency of the electron transport chain in the mitochondria, thereby reducing the generation of free radicals and preventing the leakage of electrons. Last but not least, melatonin interferes in a beneficial sense with the generation and potentiation of endogenous antioxidants (e.g., glutathione, SOD, CAT, GPx, nitric oxide synthase) (Zephy and Ahmad, 2015; Nishida, 2005). Food sources of animal origin are meat (lamb, beef, pork, fish, chicken), eggs and dairy products. Vegetable sources (e.g., corn, rice, wheat, barley, oats, strawberries, cherries, grapes, walnuts, pistachios, almonds, tomatoes, peppers, mushrooms, black/white mustard seeds, soybeans) are subject to variability in the amount of melatonin dictated by the environment in which they are grown (e.g., temperature, duration of exposure to sunlight, ripening process, agrochemical treatment) (Meng et al., 2017).

It is included in the category of hydrophilic antioxidants, exerting its effects in both aqueous and lipid environments. By reducing it to dihydrolipoate, dietary α-lipoic acid participates in the regeneration of other antioxidants (e.g., vitamins C and E, reduced glutathione), thus being considered an inducer molecule (Johansen et al., 2005). The endogenous source is a cofactor for mitochondrial α-keto acid dehydrogenases, while exogenous sources cannot be used in this sense. However, the exogenous supply of α-lipoic acid stimulates a series of biochemical reactions with pharmacotherapeutic value. There are added interactions with systemic inflammatory status, redox balance, the NRF2/kelch-like ECH-associated protein 1 pathway, glycolipid metabolism or metal chelation. α-lipoic acid is therefore considered a strong antioxidant, with insulin-mimetic and anti-inflammatory activity (Shay et al., 2009; Rochette et al., 2015; Packer et al., 1995). Food sources are muscle meat, heart, kidney and liver, and to a lesser extent fruits and vegetables. They cannot supply the entire organic requirement, thus recommending the use of food supplements as the primary source of nutrients (Shay et al., 2009).

It is a vegetable antioxidant, precursor of glutathione, usually found in onions. Its role in oxidative dynamics is bivalent, in accordance with other molecular agents of the “thiol” type. N-acetyl cysteine is therefore involved both in cleaning reactive oxygen species and hydroxyl radicals (antioxidant effect), as well as in reducing transitional metals (pro-oxidative effect) (Šalamon et al., 2019).

In conclusion, we consider it appropriate to discuss the results obtained by Neri S. et al. regarding the importance of combining antioxidants (in this case N-acetylcysteine, vitamin E and vitamin C) in counteracting oxidative stress and preventing the harmful effects of a disorganized lifestyle (Neri et al., 2005). Similar results were observed in studies on adults and regarding associations such as vitamin A-vitamin E-zinc or high doses of B complex vitamins. These combinations led to the improvement of glycemic control, β-cell function and insulin secretion, while also promoting myelination, cellular metabolism and energy storage (Ford et al., 2018; Said et al., 2020).