Adjuvant Antioxidant Research Articles

A 6-month randomized controlled trial for vitamin E supplementation in pediatric patients with Gaucher disease: Effect on oxidative stress, disease severity and hepatic complications.

Enzymatic deficiency in Gaucher disease (GD) may induce oxidative stress. Vitamin E is the nature's most effective lipid-soluble antioxidant. This prospective clinical trial assessed the oxidant-antioxidant status in Egyptian patients with GD and the efficacy and safety and of vitamin E as an adjuvant antioxidant therapy. Forty children and adolescents with GD on stable doses of enzyme replacement therapy (ERT) were enrolled. Abdominal ultrasonography and transient elastography were performed. Malondialdehyde (MDA), vitamin E, and antioxidant enzymes (reduced glutathione [GSH], superoxide dismutase [SOD], glutathione peroxidase [GPx], and peroxiredoxin 2 [PRDX2]) were assessed. Patients were compared with 40 age- and sex-matched healthy controls. Patients with GD were randomized either to receive oral vitamin E for 6 months or not. All patients with GD had significantly higher MDA levels with lower levels of vitamin E and antioxidant enzymes compared with healthy controls (p < 0.001). Vitamin E and PRDX2 were negatively correlated to severity score index (SSI), lyso GL1, and MDA. After 6 months of vitamin E supplementation, SSI and liver and spleen volumes and liver stiffness were significantly lower. Lyso GL1 and MDA were significantly decreased post-vitamin E therapy while antioxidant enzymes were significantly higher compared with baseline levels and with patients without vitamin E therapy. Oxidative stress is related to disease severity in pediatric patients with GD. A 6-month vitamin E supplementation for those patients represents a safe therapeutic adjuvant agent increasing the efficacy of ERT, reducing oxidative stress, and improving outcomes.

Oxidative stress and acute pancreatitis (Review).

Acute pancreatitis (AP) is a common inflammatory disorder of the exocrine pancreas that causes severe morbidity and mortality. Although the pathophysiology of AP is poorly understood, a substantial body of evidence suggests some critical events for this disease, such as dysregulation of digestive enzyme production, cytoplasmic vacuolization, acinar cell death, edema formation, and inflammatory cell infiltration into the pancreas. Oxidative stress plays a role in the acute inflammatory response. The present review clarified the role of oxidative stress in the occurrence and development of AP by introducing oxidative stress to disrupt cellular Ca2+ balance and stimulating transcription factor activation and excessive release of inflammatory mediators for the application of antioxidant adjuvant therapy in the treatment of AP.

L-carnitine: A novel approach in management of acute cholinesterase inhibitor insecticide poisoning.

Cholinesterase inhibitors (ChEIs) insecticide poisoning is a serious global health concern that results in hundreds of thousands of fatalities each year. Although inhibition of the cholinesterase enzyme is the main mechanism of ChEI poisoning, oxidative stress is considered the mechanism underlying the related complications. The study aimed to assess the oxidative status of the patients with ChEI insecticide poisoning and the role of L-carnitine as adjuvant therapy in their management. Human studies on the efficacy and safety of L-carnitine in treating insecticide poisoning are limited despite its growing research interest as a safe antioxidant. This prospective study was conducted on eighty patients with acute ChEIs insecticide poisoning admitted to Alexandria Poison Center, Alexandria Main University Hospital, Egypt. Patients were allocated into two equal groups randomly. The L-carnitine (LC) group received the conventional treatment (atropine & toxogonin) and LC and the standard treatment (ST) group received the standard treatment only. Outcome measures were fatality rate, the total administered dose of atropine & toxogonin, length of hospital stay, and the requirement for ICU admission or mechanical ventilation. The study results revealed that malondialdehyde (MDA) significantly decreased in the LC group. Cholinesterase enzyme levels increased significantly after treatment in the LC group than in the ST group. The LC group needed lower dosages of atropine and toxogonin than the ST group. Also, the LC group showed no need for ICU admission or mechanical ventilation. The study concluded that LC can be considered a promising adjuvant antioxidant treatment in acute ChEIs pesticide poisoning.

Efficacy of addition of the anti-inflammatory, IV glutathione to standard ketamine IV therapy in major depressive disorder

Ketamine, a N-methyl-D-aspartate (NMDA) antagonist, is used for treatment-resistant depression (TRD). Recent studies have shown that there are increased levels of pro-inflammatory cytokines in individuals with major depressive disorder (MDD) and those with higher levels of oxidative stress markers have a decreased or null response to conventional antidepressants. Glutathione (GSH) as an antioxidant adjuvant to ketamine has not been well studied. This double-blind study with 30 patients divided into 2 groups of 15 each, aimed to determine if GSH, added to standard ketamine infusion (GSH+K), rendered better outcomes in MDD patients versus patients receiving ketamine infusions with a normal saline placebo (K+NS). There were significant drops in BDI-II scores from day 1 to day 14, PHQ- scores from day 1 to day 14 and PHQ-9 scores day 14 to day 28, suggesting the overall treatment was effective. There were no statistically significant differences between the groups over time. However, a sustained improvement in depressive symptoms was observed for 14 days post-infusion in both groups.

In Vitro Evaluation of the Antioxidant Capacity of 3,3-Disubstituted-3H-benzofuran-2-one Derivatives in a Cellular Model of Neurodegeneration.

Oxidative stress represents a hallmark for many degenerative pathologies of the Central Nervous System. Throughout life, the constant pressure of noxious stimuli and/or episodes of traumatic events may expose the brain to a microenvironment where the non-balanced reactive oxygen species inevitably lead to neuronal loss and cognitive decline. HO-1, a 32 kDa heat-shock protein catalyzing the degradation of heme into carbon monoxide (CO), iron and biliverdin/bilirubin is considered one of the main antioxidant defense mechanisms playing pivotal roles in neuroprotection. Restoring the redox homeostasis is the goal of many natural or synthetic antioxidant molecules pursuing beneficial effects on brain functions. Here, we investigated the antioxidant capacity of four selected benzofuran-2-one derivatives in a cellular model of neurodegeneration represented by differentiated SH-SY5Y cells exposed to catechol-induced oxidative stress. Our main results highlight how all the molecules have antioxidant properties, especially compound 9, showing great abilities in reducing intracellular ROS levels and protecting differentiated SH-SY5Y cells from catechol-induced death. This compound above all seems to boost HO-1 mRNA and perinuclear HO-1 protein isoform expression when cells are exposed to the oxidative insult. Our findings open the way to consider benzofuran-2-ones as a novel and promising adjuvant antioxidant strategy for many neurodegenerative disorders.

Possible prospects for the combined administration of antidepressants and antioxidants in neurological patients

Antidepressants (ADs) are a group of drugs whose action primarily consists of stimulating neurotransmitter systems (dopaminergic, serotonergic and noradrenergic systems). Neurologists prescribe them for the treatment of post-stroke and other depression, chronic pain syndromes, neuropathic pain, panic attacks, correction of post-Covid syndrome, for the prevention of migraines, Parkinson’s disease and neurodegenerative diseases, including Alzheimer’s disease. However, even with appropriate therapy, many people with depressive disorder may experience subsyndromal symptoms and complete remission is short-lived, so there is a need to use other therapeutic approaches. Combining two or more antidepressants may target different neurochemical pathways while increasing the risk of side effects and the development of resistance. Therefore, the search for alternative treatments is urgent, and oxidative stress appears to be an interesting therapeutic target. The combined use of AD and antioxidants may provide an effective and safe approach to enhancing antidepressant effects by synergistically enhancing certain antidepressant activities (eg, enhancing monoamine reuptake inhibition) or by additive pharmacological effects, such as adjusting neurotransmitters and reducing the damaging effects of active agents. forms of oxygen. There are a number of clinical studies to prove the effectiveness of the combined use of antioxidants and antioxidants. In the group of patients receiving a combination of antioxidants and antidepressants/anti-anxiety drugs, there was a better regression of symptoms and severity of depression, which probably indicates the usefulness of adjuvant antioxidant therapy with regular psychotropic treatment. The use of combination drugs in complex therapy with blood pressure seems to be a promising direction and requires further study.

Testicular torsion in vivo models: Mechanisms and treatments.

Testicular torsion is a condition in which a testis rotates around its longitudinal axis and twists the spermatic cord. This in turn results in a significant decrease in blood flow and perfusion of testicular tissue. During Testicular torsion, the testicular tissue is affected by ischemia, heat stress, hypoxia, and oxidative and nitrosative stress. The testicular torsion should be considered an emergency condition and surgical intervention (testicular detorsion ) as the sole treatment option in viable cases involves counter-rotation on twisted testes associated, when possible, to orchipexy, in order to avoid recurrence. Possible testicular detorsion side-effects occur due to reperfusion and endothelial cells injury, microcirculation disturbances, and intense germ cells loss. To discuss testicular torsion surgery-based methods, different time frames for testicular torsion induction, and the associated pathophysiology by emphasizing cellular and molecular events as well as different therapeutic agent applications for testicular torsion. We reviewed all original research and epidemiological papers related to testicular torsion condition. Testicular torsion causes germ cell necrosis, arrested spermatogenesis, and diminished testosterone levels, with consequent infertility. Among different involved pathophysiological impacts, testicular torsion/detorsion-induced ischemia seems to play the key role by leading the tissue toward other series of events in testis. Numerous studies have used adjuvant antioxidants, calcium channel blockers, anti-inflammatory agents, or vasodilating agents in order to decrease these effects. To the best of our knowledge, no previously conducted study examined therapeutical agents' beneficial effects post clinical I/R condition in humans. Different agents targeting different pathophysiological conditions were used to ameliorate the ischemia/reperfusion-induced condition in animal models, however, none of the administrated agents were tested in human cases. Although considering testicular detorsion surgery is still the golden method to reverse the testicular torsion condition and the surgical approach is undeniable, the evaluated agents with beneficial effects, need to be investigated furthermore in clinical conditions. Thus, furthermore clinical studies and case reports are required to approve the animal models proposed agents' beneficial impacts.

Comparison of Efficacy of Topical Application of Bleomycin with Adjuvant Antioxidants vs. Topical Curcumin Oral Gel with Adjuvant Antioxidants in the Treatment of Oral Leukoplakia

Introduction: Oral leukoplakia (OL) is an oral premalignant disorder (OPMD) defined as a white plaque of questionable risk, and the diagnosis is by exclusion. Aim: We aimed to compare the effectiveness of topical bleomycin with that of topical curcumin in patients with oral leukoplakia (OL). Materials and Methods: Bleomycin was assigned for group A and curcumin for group B patients. Both the drugs were applied topically with adjuvant oral antioxidants for both groups. Results: Group A (n = 10) patients showed partial to complete resolution of the leukoplakic lesions with a P value of 0.01, whereas in group B (n = 10) patients, resolution of the clinical lesion was not substantial, but a reduction of the erythroid component was observed along with histopathological improvement of dysplasia with a P value of 0.01. Conclusion: Comparatively, bleomycin was more efficient in producing clinical and histopathologic resolution of OL than curcumin.

The Effect of Green Tea as an Adjuvant to Enzyme Replacement Therapy on Oxidative Stress in Fabry Disease: A Pilot Study.

Enzymatic replacement therapy (ERT) is not very effective in halting the progression of Fabry disease (FD) toward cardiovascular (CV)-renal remodeling, particularly in case of late diagnosis. FD patients have increased oxidative stress (OS), critical for the induction of CV-renal remodeling. We investigated the effects of an adjuvant antioxidant treatment to ERT on OS and the possible advantages for related complications. OS was evaluated in 10 patients with FD before ERT, after 12 months of ERT, and after 6 months of adjuvant green tea (GT) to ERT by the following experiments: expression of p22phox; phosphorylation state of MYPT-1 and ERK 1/2 (by western blotting); and quantification of malondialdehyde (MDA) and heme oxygenase (HO)-1 levels (by ELISA). p22phox and MYPT-1 phosphorylation decreased after ERT and significantly further decreased after GT. ERK 1/2 phosphorylation and MDA levels remained unchanged after ERT, but significantly decreased after GT. HO-1 significantly increased after ERT and further increased after GT. This study provides preliminary data highlighting the antioxidant effect exerted by ERT itself, further amplified by the adjuvant antioxidant treatment with GT. The results of this study provide evidence of the positive effect of early additive antioxidant treatment to reduce OS and prevent/alleviate cardio and cerebrovascular-renal complications related to OS.

Effectiveness of Omega-3 Fatty Acids and Spirulina as an Adjuvant Antioxidant to Corticosteroid in the Treatment of Oral Submucous Fibrosis – A Comparative Study

Introduction: Oral submucous fibrosis (OSMF) is a chronic insidious and a well-recognized potentially malignant disorder of the oral cavity. Due to its high morbidity and malignant transformation rate, relentless efforts have been made to improve effective management, despite not much improvement in the prognosis. Omega 3 polyunsaturated fatty acids have been reported to have anti-inflammatory properties. With its antioxidant, anti-inflammatory, and immunomodulating properties, Spirulina has shown promising results in the management of OSMF. This present study was conducted to compare the effectiveness of Omega-3 fatty acids and Spirulina in the management of OSMF. Aims and Objectives: To find out and compare the effectiveness of Omega-3 fatty acids and spirulina in the management of OSMF. Methods and Material: 40 OSMF patients with clinically diagnosed OSMF were selected and divided into two groups. Group A was given biweekly intralesional injections of 1.5 ml Dexamethasone in 4 mg/1 ml and Hyaluronidase 1500 IU mixed with Lignocaine 0.5 ml for six weeks and with omega-3 fatty acid capsules 1 gm three times daily for three months. Group B received similar intralesional injections but with spirulina 500 mg twice daily for three months. All the patients were followed up every month for 3 months and then after six months. Results: Both groups improved mouth opening, cheek flexibility, and VAS burning sensation except tongue protrusion (p &lt; 0.05). When the efficacy was compared between two drugs, statistically insignificant results were found for mouth opening, tongue protrusion, cheek flexibility, and burning sensation. Conclusion: Omega 3 and Spirulina can be effective adjunctive treatment options in patients with OSMF to reduce subjective symptoms. Statistically, significant improvement was seen in both groups.

The Significance of Nitrosative Pressure in Underlying Pathophysiology and The Pharmacologic Therapy of Non-Communicable Disease with Fessional and Antioxidant Potential

Chronic stress (OS) can degrade a range of substances and cellular structures, impairing organ and system performance. Endogenous and external pathways contribute to the accumulation of OS in the body. There is mounting evidence that OS has a role in the physiopathology of various chronic disorders that require continuous pharmaceutical treatment. Prolonged therapy may affect systemic OS. We explore the role of OS in the pathophysiology of several chronic diseases, the pro- or antioxidant effects of their pharmaceutical therapies, and potential adjuvant antioxidant alternatives in this review. High blood pressure, arteriosclerosis, and diabetes mellitus raise the risk of developing cardiovascular disease. Antihypertensive, lipid-lowering, and hypoglycemic medications contribute to risk reduction while also providing an antioxidant benefit. In autoimmune systemic inflammatory illnesses such as rheumatoid arthritis, methotrexate treatment has a dual effect of boosting OS synthesis and causing mitochondrial malfunction. However, it may also contribute indirectly to reducing systemic OS caused by inflammation. Medications used to treat neurodegenerative illnesses have been shown to inhibit systems involved in producing and balancing reactive oxygen species (ROS). On the other hand, immunosuppressive treatments for cancer or human immunodeficiency virus infection enhance ROS generation, resulting in severe oxidative damage in several organs and systems in the absence of welldocumented exogenous antioxidant delivery

Evaluation of antioxidant supplementation in must on the development and potential reduction of different compounds involved in atypical ageing of wine using HPLC-HRMS

Atypical aging of white wines (ATA) is an off-flavour characterised by rapid loss of fruity aromas and the development of unpleasant odours.This study aims to evaluate the effectiveness of different oenological adjuvants (4-ethylcatechol, 4-methylcatechol, gentisic acid, hydroxytyrosol, ascorbic acid, glutathione, ellagic acid, gallic acid, galla tannin, ellagic tannin, quebracho, grape tannins) added to musts before fermentation for preventing the possible development of ATA. High resolution mass spectrometry made it possible to quantify and qualify free and conjugated IAA in wine at the end of the fermentation and subsequently 2-aminoacetophenone (AAP) was quantified after the force ageing period (6 days at 40 °C). Ascorbic acid was confirmed as the most appropriate antioxidant adjuvant which can be used for ATA defect prevention. With an almost comparable effect, gallotannin addition prevented AAP production to exceed 1 μg/L. A predicted model (ANCOVA) indicated that over 80% of the variability of potential AAP formation in wines was explained by the amount of precursors, grape variety and antioxidant treatment. Moreover, a suspect screening approach made it possible to study the kinetic formation and the consumption of the reaction metabolites formed during the oxidative degradation of IAA leading to AAP.

Protective effect of n-acetyl-L-cysteine and rosuvastatin against oxidative stress in fibroblasts from asymptomatic patients with X-ALD: a preliminary study

Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusion: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease.

New Insight Into the Cardioprotective Effects of Allium ursinum L. Extract Against Myocardial Ischemia-Reperfusion Injury.

This study aimed to estimate the effects of increasing doses of Allium ursinum methanol extract on cardiac ischemia/reperfusion injury (I/R) with a special emphasis on the role of oxidative stress. Fifty rats were randomly divided into five groups (10 animals per group) depending on the applied treatment as follows: sham, rats who drank only tap water for 28 days and hearts were retrogradely perfused for 80 min without I/R injury, I/R, rats who drank only tap water for 28 days and hearts were exposed to ex vivo I/R injury and rats who consumed increasing doses of A. ursinum 125, 250, and 500 mg/kg for 28 days before I/R injury. Hearts from all rats were isolated and retrogradely perfused according to the Langendorff technique. Parameters of oxidative stress were spectrophotometrically measured in blood, coronary venous effluent, and heart tissue samples. Intake of wild garlic extract for 28 days significantly contributed to the recovery of cardiac function, which was reflected through preserved cardiac contractility, systolic function, and coronary vasodilatory response after ischemia. Also, wild garlic extract showed the potential to modulate the systemic redox balance and stood out as a powerful antioxidant. The highest dose led to the most efficient decrease in cardiac oxidative stress and improve recovery of myocardial function after I/R injury. We might conclude that wild garlic possesses a significant role in cardioprotection and strong antioxidant activity, which implicates the possibility of its use alone in the prevention or as adjuvant antioxidant therapy in cardiovascular diseases (CVD).

The protective role of Coenzyme Q10 in metallothionein-3 expression in liver and kidney upon rats’ exposure to lead acetate

Metallothionein-3 (MT3) is an antioxidant protein that alters after exposure to heavy metals. In this study, we investigated the hepatic and renal expression of MT3 gene following exposure to lead acetate (PbAc) alone and PbAc plus CoQ10 as an adjuvant antioxidant. Twenty-four rats were allocated into three groups, including control, PbAc (free access to drinking water contaminated with PbAc at 1g/100ml), and PbAc plus CoQ10 (10mg/kg/day Oral). After 28 consecutive days of treatment, the mRNA expression of MT3 and Cyt-c genes and MT3 protein levels were assessed using real-time PCR and immunosorbent assay. The serum lipid profile was also monitored in the three groups. PbAc exposure significantly reduced the hepatic and renal MT3 mRNA and protein expression compared to the control group. This reduction was significantly increased with addition of CoQ10 to levels near those of the control group. The hepatic and renal expression of Cyt-c mRNA increased after treatment with PbAc, while such effect was reversed after addition of CoQ10. Alteration in lipid profile including increased cholesterol and low-density lipoprotein levels were observed after PbAc exposure which were counteracted by CoQ10. Our results confirm the cytotoxic effects of acute lead exposure manifested as changes in the serum lipid profile and cellular levels of Cyt-c mRNA. These cytotoxic effects may have been caused by decreased MT3 gene expression and be reduced by the protective role of CoQ10.

The potential hepatoprotective effect of metformin in hepatitis C virus-infected adolescent patients with beta thalassemia major: Randomised clinical trial.

Iron overload-induced oxidative stress and transfusion-acquired hepatitis C virus (HCV) infection are the main reasons of liver damage in beta thalassemia major (β-TM). Based on metformin's hepatic benefits in nondiabetic populations, the study aims to investigate the safety and the potential hepatoprotective effect of metformin in HCV-infected β-TM adolescent patients. This was a prospective, randomised, parallel, controlled, open-label study in which 60 HCV-infected β-TM adolescent patients aged 11 to 18years and receiving no antiviral therapy were selected and randomly assigned to treatment or control group in 1:1 allocation. Both groups were receiving β-TM standard-of-care regimen, whereas metformin (500mg, twice daily) was added to the treatment group's regimen only. Patients were prospectively followed up for 6months with assessment of liver biochemical profile, oxidative stress markers, liver fibrosis, clinical symptom improvement and metformin's adverse effects. Aspartate aminotransferase serum level decreased significantly over time in the treatment group only (P=.013). However, improvement was not clinically significant and did not attain normality. Change in total antioxidant capacity and malondialdehyde serum levels indicated significantly improved oxidative stress status in the treatment group versus significant deterioration in the control group (P<.001). Fibrosis grade improvement was observed in 14 patients in the treatment group versus one improved case in the control group. The use of metformin in HCV-infected β-TM adolescent patients as an adjuvant antioxidant hepatoprotective agent is promising and can improve liver damage.

In vitro activities of Acacia nilotica (L.) Delile bark fractions against Oral Bacteria, Glucosyltransferase and as antioxidant

BackgroundDental caries and periodontal disease are the most common chronic infectious oral diseases in the world. Acacia nilotica was commonly known in Sudan as Garad or Sunt has a wide range of medicinal uses. In the present study, antibacterial activity of oral bacteria (Streptococcus sobrinus and Porphyromonas gingivalis), inhibitory activity against glucosyltransferase (GTF) enzyme and antioxidant activity were assayed for methanolic crude extract of A. nilotica bark and its fractions.MethodsMethanoilc crude extract of A. nilotica bark was applied to a Sephadex LH-20 column and eluted with methanol, aqueous methanol, and finally aqueous acetone to obtain four fractions (Fr1- Fr4). Furthermore, the crude extract and fractions were subjected to analytical high performance liquid chromatography (HPLC). The crude extract and its fractions were assayed for antibacterial activity against S. sobrinus and P. gingivalis using a microplate dilution assay method to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), as well as GTF inhibition and antioxidant activity using ABTS radical scavenging method.ResultsFractions (Fr1 and Fr2) exhibited MIC values of 0.3 mg/ml against the P. gingivalis. Additionally, Fr2 displayed MBC value of 1 mg/ml against two types of bacteria. Fr4 showed an especially potent GTF inhibitory activity with IC50 value of 3.9 μg/ml. Fr1 displayed the best antioxidant activity with IC50 value of 1.8 μg/ml. The main compound in Fr1 was identified as gallic acid, and Fr2 was mostly a mixture of gallic acid and methyl gallate.ConclusionsThe results obtained in this study provide some scientific rationale and justify the use of this plant for the treatment of dental diseases in traditional medicine. A. nilotica bark, besides their antibacterial potentiality and GTF inhibitory activity, it may be used as adjuvant antioxidants in mouthwashes. Further studies in the future are required to identify the rest of the active compounds.

Attenuation of Clozapine (Clozaril®) Toxicity in vitro Using Edaravone as an Antioxidant Adjuvant

Attenuation of Clozapine (Clozaril®) Toxicity in vitro Using Edaravone as an Antioxidant Adjuvant

The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases.

Oxidative stress (OS) has the ability to damage different molecules and cellular structures, altering the correct function of organs and systems. OS accumulates in the body by endogenous and exogenous mechanisms. Increasing evidence points to the involvement of OS in the physiopathology of various chronic diseases that require prolonged periods of pharmacological treatment. Long-term treatments may contribute to changes in systemic OS. In this review, we discuss the involvement of OS in the pathological mechanisms of some chronic diseases, the pro- or antioxidant effects of their pharmacological treatments, and possible adjuvant antioxidant alternatives. Diseases such as high blood pressure, arteriosclerosis, and diabetes mellitus contribute to the increased risk of cardiovascular disease. Antihypertensive, lipid-lowering, and hypoglycemic treatments help reduce the risk with an additional antioxidant benefit. Treatment with methotrexate in autoimmune systemic inflammatory diseases, such as rheumatoid arthritis, has a dual role in stimulating the production of OS and producing mitochondrial dysfunction. However, it can also help indirectly decrease the systemic OS induced by inflammation. Medicaments used to treat neurodegenerative diseases tend to decrease the mechanisms related to the production of reactive oxygen species (ROS) and balance OS. On the other hand, immunosuppressive treatments used in cancer or human immunodeficiency virus infection increase the production of ROS, causing significant oxidative damage in different organs and systems without widely documented exogenous antioxidant administration alternatives.

Studying the effect of large neutral amino acid supplements on oxidative stress in phenylketonuric patients.

Background Oxidative stress may be one of the causes responsible for mental retardation in phenylketonuria (PKU) patients. Phenylalanine (Phe) reduces antioxidant defense and promotes oxidative stress by causing increase in reactive oxygen-nitrogen species. Our study aimed to investigate the effect of different treatments (amino acid mixture/large neutral amino acid [LNAA] supplements) on oxidative stress which are applied to late-diagnosed patients. To the best of our knowledge, this is the first study to investigate the effect of LNAA supplements on oxidative stress. Methods Twenty late-diagnosed classic PKU patients were included in this study. Patients were classified into two groups: patients under Phe-restricted diet and using Phe-free amino acid mixtures (Group I) (mean age: 13.8 ± 2.8), and patients taking LNAA supplements (Group II) (mean age: 14.8 ± 3.8). Healthy controls (mean age: 13.6 ± 4.8) with ages consistent with the ages of the patients in the experimental groups were included. Results Glutathione peroxidase is lower in patients of taking LNAA supplements than the control group (p = 0.022). Coenzyme Q10 is lower in patients of using Phe-free amino acid mixtures than the control group and it is significantly higher in Group II than Group I (p = 0.0001, p = 0.028, respectively). No significant differences were detected in total antioxidant status, total oxidant status, oxidative stress index, paraoxonase 1 and L-carnitine levels. Conclusions Different treatments affect oxidative stress parameters in PKU patients. In this study, although patients were followed up with classic PKU, patient-specific adjuvant antioxidant therapies should be implemented in response to oxidative stress.