Effect Of Lipoic Acid Research Articles

Are the beneficial effects of ‘antioxidant’ lipoic acid mediated through metabolism of reactive sulfur species?

The health benefits of lipoic acid (LA) are generally attributed to mitigating the harmful effects of reactive oxygen species (ROS). ROS are chemically similar to reactive sulfur species (RSS) and signal through identical mechanisms. Here we examined the effects of LA on RSS in HEK293 cells using H2S and polysulfide (PS) specific fluorophores, AzMC and SSP4. We show that LA concentration-dependently increased both H2S and PS. Physioxia (5% O2) augmented the effects of LA on H2S production but decreased PS production. Thiosulfate, a known substrate for reduced LA, and an intermediate in the catabolism of H2S enhanced the effects of LA on H2S and PS production. Inhibiting peroxiredoxins with conoidin A and gluraredoxins with tiopronin augmented the effects of LA on PS and H2S, respectively while decreasing glutathione with buthionine-sulfoximine (BSO) or diethyl maleate (DEM) decreased the stimulatory effect of LA on H2S production but augmented LA's effect on PS. Aminooxyacetate (AOA) and propargylglycine (PPG), inhibitors of H2S production from cysteine partially inhibited LA augmentation of H2S production and further decreased the LA effect when applied concurrently with BSO and DEM. The selective and cell-permeable H2S scavenger, SS20, inhibited the effects of LA on cellular H2S. Estimates of single-cell H2S production suggest that 0.1–0.2% of O2 consumption is used to metabolize H2S and these requirements may increase to 1–2% with 1 mM LA. Collectively, these results suggest that LA rescues H2S from irreversible oxidation and that the effects of LA on RSS directly confer antioxidant, anti-inflammatory and cytoprotective responses. They also suggest that TS may be an effective supplement to increase the efficacy of LA in clinical settings.

Effect of lipoic acid supplementation on gene expression and activity of glutathione S-transferase enzyme in infertile men

Oxidative stress has become the focus of interest as a potential cause of male infertility. We evaluate effects of lipoic acid (LA) supplementation on glutathione S-transferase (GST) expression. This randomized, triple-blind, placebo-controlled clinical trial was conducted on 44 infertile males with idiopathic asthenozoospermia. Men were randomized to receive 600 mg LA or placebo once daily for 12 weeks and semen samples and venous blood samples were obtained. GST expression, reactive oxygen species (ROS) levels, GST activity and reproductive hormone profiles were also measured. GST expression in the intervention group were significantly higher than the control group. Also, at the end of the study, GST activity increased, and ROS levels decreased significantly compared to the baseline. Additionally, the intervention group showed an increase in testosterone and decrease in serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin after 12 weeks, but this difference was not significant. We conclude a 12-week treatment with LA leads to improvements in reproductive hormones in serum, and significantly reduces the generation of ROS and increases the gene expression and activity of GST in seminal fluid.

Ameliorative Effect of Lipoic Acid on Cadmium Induced Hepatotoxicity and Nephrotoxicity in Rats

Ameliorative Effect of Lipoic Acid on Cadmium Induced Hepatotoxicity and Nephrotoxicity in Rats

Effects of lipoic acid and ω-3 long-chain polyunsaturated fatty acids on the kidney in the ovariectomized rat model of menopause.

The loss of antioxidant protection from estrogen during menopause may lead to oxidative stress in the kidneys. Thus, antioxidant supplementation may potentially decrease the menopause-derived oxidative stress. The aim of this study was to evaluate the effect of α-lipoic acid (LA) and ω-3 long-chain polyunsaturated fatty acids on the redox profile of the kidneys in the ovariectomized rat model of menopause. We assessed oxidative damage markers and antioxidant defenses in the kidneys of ovariectomized rats supplemented with LA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Animals received 3 mo of dietary supplementation. Ovariectomy did not increase the levels of the damage markers carbonyl and malondialdehyde. EPA supplementation increased carbonyl and malondialdehyde levels. Ovariectomy increased fumarase activity but did not affect the levels of vitamin C, glutathione, and glutathione S-transferase activity. LA, DHA, and EPA supplementation decreased fumarase activity, but increased the levels of vitamin C, glutathione, and glutathione S-transferase activity. Vitamin E, superoxide dismutase, glutathione peroxidase, and peroxide consumption were not affected by ovariectomy or supplementation. The results suggest that ovariectomy did not affect the redox profile in the kidneys. LA, DHA, and EPA supplementation increased certain endogenous antioxidants; however, EPA may have a prooxidant effect on the kidneys.

Effects of lipoic acid on primary murine microglial cells

The anti-oxidant lipoic acid (LA) is beneficial in murine models of multiple sclerosis (MS) and has recently been shown to slow brain atrophy in secondary progressive MS. The mechanism of these effects by LA is incompletely understood but may involve effects on microglia. The objective of this study is to understand how LA affects microglial cells. We cultured primary microglial cells from C57BL/6 adult mice brains and stimulated the cells with lipopolysaccharide (LPS) and interferon gamma (IFN-γ) in the presence or absence of LA. We demonstrate the inhibition of phagocytosis, rearrangement of actin, and formation of membrane blebs in stimulated microglia in the presence of LA. These experiments suggest that LA causes changes in microglial actin, which may lead to alterations in phagocytosis, mobility, and migration.

Lipoic Acid Prevents Renal Dysfunction in Experimental Diabetes

IntroductionDiabetic nephropathy affects approximately 30–40% of patients with type 1 diabetes mellitus and 8% to 10% of patients with type 2 diabetes, and is the main cause of end‐stage renal disease, requiring hemodialysis or renal transplantation.ObjectiveThe study evaluated the effect of lipoic acid for 60 days in the prevention of experimental diabetic nephropathy in diabetic rats. Male Wistar rats were divided into three groups: euglycemic (eugly; n = 12), untreated diabetic (Diab; n = 6), and diabetic treated with lipoic acid (AL) 20mg/kg every 12 hours Orally (Diab + AL; n = 12) for 60 days. The animals were induced to diabetes with intraperitoneal injection of streptozotocin (STZ) (65 mg/kg, i.p), diluted in citrate buffer (pH 4.5). The control group received only citrate buffer (0.1mL/100g; i.p). Renal function was evaluated in metabolic cages on days 0, 15, 30, 45 and 60, with collection of urine and blood. After 60 days, all the animals were assigned to functional studies of renal hemodynamics and pressure natriuresis, in addition to molecular marker studies of diabetic nephropathy.ResultsThe animals studied presented classic diabetes characteristics such as hyperglycemia, maintained throughout the experimental protocol, polyuria, polydipsia and glycosuria, whose treatment with lipoic acid, was able to improve all these alterations. After 60 days, they presented albuminuria, which was attenuated with AL treatment. The excreted fraction of sodium, was increased 4‐fold in the Diab group and was attenuated in the AL‐treated group. The natriuresis increased about 7‐fold in the Eugli group during the period of increased renal perfusion pressure, however, it was impaired by 65% in the control non‐treated diabetic animals. The AL treated group, however, had normal pressure natriuresis. The renal concentration of gluthatione (GSH) decreased by 48% in the diabetic group when compared to the Eugli group, and the AL treatment restored the GSH levels to control values. The lipoperoxidation marker, malondialdehyde, was increased in the Diab group (68%) but was normal in the AL‐treated diabetic group.ConclusionTreatment with lipoic acid is able to prevent the great majority of changes caused during the course of experimental diabetes, and could be an alternative to the composition of a primary prevention treatment in conjunction with metabolic control drugs.Support or Funding InformationFUNCAP, CAPES and CNPqThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Alpha-lipoic acid alleviates lipopolysaccharide-induced liver damage in rats via antioxidant effect

Objective: The effect of lipoic acid (LA), which is considered to be a potential antioxidant, on oxidative stress parameters in liver tissue damage has not been sufficiently investigated. Therefore, we aimed to investigate the relationship of LA with oxidant and antioxidant parameters in lipopolysaccharide (LPS) induced liver damage in rats. Methods: First group (n=10) was injected a single dose of 20 mg/kg saline (control), second group (n=10) was injected a single dose of 20 mg/kg LPS (LPS) and third group (n=10) was injected a single dose of 20 mg/kg LPS at the end of third day of 10 mg/kg/day LA injection (LA+LPS). The glutathione peroxidase (GPX), catalase (CAT) and superoxide dismutase (SOD) activities and the levels of malondialdehyde (MDA) were determined by spectrophotometric method. 3-Nitrotyrosine (3-NT) level was measured by high performance liquid chromatography. Results: It was found that 3-NT and MDA levels were significantly lower in LA+LPS group than those of LPS group. Moreover, it was found that antioxidant enzyme activity values of LA+LPS approached to the values of control group. Conclusion: These findings indicate that the oxidant/antioxidant status is balanced in the LA group. Therefore, it may be suggested that LA supplementation to be beneficial for preventing oxidative stress in LPS-induced liver damage in rats.

Evaluation the Effect of Gentamicin on Fertility of Male Rats & Probable Protective Role of Lipoic Acid

The aim of our research was to investigate the probable preventive effect of lipoic acid in fertility of rats against gentamicin toxicity. Twenty four male rat divided into four groups each group have 6 animals were treated as follows: untreated control animals (group1), treated with lipoic acid 600 mg/kg orally (group 2), treated with gentamicin 80 mg/kg intraperitonialy (group 3) & treated with lipoic acid combination with gentamicin (group 4) all these groups treated for four weeks. The result revealed physiological & histopathological changes in animals treated with gentamicin, there are significant decrease in testosterone & LH levels, also there are significant decrease in sperm count, viability, motility & significant increase in sperm abnormality. On the other hand, lipoic acid when given with gentamicin lead to return all these alteration near closely to the normal states. In conclusion, lipoic acid causes enhancement the alteration induced by gentamicin in male reproductive system of rat.

Effects of lipoic acid on walking performance, gait, and balance in secondary progressive multiple sclerosis

BackgroundGait and balance impairment is common in secondary progressive multiple sclerosis (SPMS). Lipoic acid (LA), an over-the-counter antioxidant, is effective in MS animal models and may improve walking speed, but effects on mobility are unreported. ObjectiveExamine the effects of 1200 mg daily oral dose of LA versus placebo (PLA) on gait and balance in a 2-year, randomized, double-blind pilot study. Methods134 participants were screened for eligibility before assignment to LA (n = 28) or PLA (n = 26). Included here were, 21 participants with SPMS who took LA (N = 11) or PLA (N = 10) capsules for 2 years (enrolled May 2, 2011 – August 14, 2015) and completed all tasks without the use of an assistive device. Participants completed the Timed Up and Go (TUG) and quiet standing tasks every 6 months while wearing inertial sensors (APDM Opals) to quantify mobility. ResultsLA had a medium effect on time to complete TUG at 2 years (g = 0.51; 95% CI = -0.35, 1.38). In a subset of 18 participants with less disability (EDSS < 6, no use of ambulatory device), turning time was significantly shorter with LA (p = 0.048, Δ= 0.48 s). No differences in balance metrics were found between groups. ConclusionsLA had an effect on walking performance in people with SPMS, particularly in those with lower baseline disability. Trial RegistrationLipoic Acid for Secondary Progressive Multiple Sclerosis https://clinicaltrials.gov/ct2/show/NCT01188811?term=spain+lipoic+acid&rank=1 NCT0118881.

KADMİYUMA MARUZ BIRAKILAN DİYABETİK RATLARA ALFA LİPOİK ASİT VE İNSÜLİN UYGULANMASININ OLASI DÜZENLEYİCİ ETKİLERİ

OBJECTIVE: Environmental exposure to the cadmium (Cd), is associated with hyperglycemia and reduced serum insulin. This investigation was planned to assess the effects of Lipoic Acid (LA) and insulin on glycolytic enzymes, liver marker enzymes and lipids in Cd exposed diabetic rats. MATERIAL AND METHODS: Male Wistar rats were separated into 7 groups (n=8 in each group). Groups were designed as control, diabetic control, diabetic + CdCl2, diabetic + insulin, diabetic + CdCl2 + insulin, diabetic + CdCl2 + LA, anddiabetic + CdCl2 + insulin + LA groups. Type 1 diabetes was established by intraperitoneal (i.p.) injection of streptozotocin (STZ) (65 mg/kg) into 6 groups. Insulin (4 IU/kg/day) was given subcutaneously (s.c.) to insulin treated groups. CdCl2 (1,2 mg/kg/day) was given s.c. to CdCl2 treated groups. LA (100 mg/kg/day) was given i.p. to LA treated groups. CdCl2, LA, and insulin treatment were started 2 days after intraperitoneal STZ injection and continued for 3 weeks. Serum glucose, AST, ALT, BUN, LDL, HDL, and TG levels and liver hexokinase (HK), pyruvate kinase (PK), whole blood HbA1c level, and Na+/K+ATPase activity were evaluated. RESULTS: In diabetic group, serum glucose, HbA1c, TG, LDL, AST, ALT, ALP, and BUN levels were higher than cont- rol, but HDL was lower. In liver tissue, activities of Na+/ K+ATPase, HK and PK activities were decreased in dia- betic control group. PK, HK and Na+/K+ATPase activities were increased in liver in diabetic+CdCl2 and Diabeti- c+Insulin+CdCl2 groups. An increase was determined in activities of HK, PK, and Na+/K+ATPase in insulin and LA treated groups compared with diabetic control group. CONCLUSIONS: These results suggest that application of insulin and LA could be an effective therapeutic intervention against liver injury caused by Cd and STZ.

Beneficial Effects of Lipoic Acid on Post-burn Hypertrophic Scarring Model

Beneficial Effects of Lipoic Acid on Post-burn Hypertrophic Scarring Model

α-Lipoic acid inhibits the migration and invasion of breast cancer cells through inhibition of TGFβ signaling

AimsInvasion and metastasis are the main cause of mortality in breast cancer. Hence, novel therapeutic interventions with high specificity toward invasion and metastasis are necessary. α-Lipoic acid showed antiproliferative and cytotoxic effects on several cancers including breast cancer. However, the effect of lipoic acid on breast cancer metastasis remains unclear. Main methodsIn the present study, we examined the effects of lipoic acid on the migration and invasion of MDA-MB-231 and 4T1 breast cancer cells. Key findingsOur data showed that lipoic acid effectively inhibited the colony forming ability of highly invasive MDA-MB-231 and 4T1 cells. Moreover, the nontoxic concentrations of lipoic acid significantly reduced the migration of breast cancer cells. Lipoic acid also inhibited the TGFβ-induced angiopoietin-like 4 (ANGPTL4) expression and reduced the activity of matrix metalloproteinase-9 (MMP-9), an enzyme involved in invasion and metastasis, in both the cell lines. The inhibition of cell migration by lipoic acid is accompanied by the downregulation of FAK, ERK1/2 and AKT phosphorylation, and inhibition of nuclear translocation of β-catenin. SignificanceOur data demonstrated that lipoic acid inhibited the migration and invasion of metastatic breast cancer cells at least in part through inhibiting ERK1/2 and AKT signaling. Thus, our findings show that the inhibition of TGFβ signaling is a potential mechanism for the anti-invasive effects of lipoic acid.

The effects of lipoic acid and methylprednisolone on nerve healing in rats with facial paralysis

Objective: To investigate the effects of lipoic acid and methylprednisolone on nerve healing in rats with traumatic facial paralysis.Materials and methods: The rats were randomly divided into four groups, with six rats in the control group and eight each in the remaining three groups. The buccal branch of the facial nerve in all groups except the control group was traumatized by a vascular clamp for 40 minutes. Group 1 was given lipoic acid (LA), Group 2 was given methylprednisolone (MP), and Group 3 was given lipoic acid and methylprednisolone (LA + MP) for one week. Nerve stimulus thresholds were measured before trauma, after trauma and at the end of the one week treatment period.Results: When the groups were compared with each other, post-treatment threshold levels of LA + MP were significantly lower than LA. Although post-treatment threshold levels of LA and MP were still higher than the control group, there was no significant difference between LA + MP and control values (p > .05).Conclusion: Lipoic acid has a positive effect on nerve healing and can enhance the effect of methylprednisolone treatment. It is a good alternative in cases where methylprednisolone cannot be used.

Effect of the Antioxidant Lipoic Acid in Aortic Phenotype in a Marfan Syndrome Mouse Model.

Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS. An unprecedented finding in MFS mice analyzed by OCT was the occurrence of focal inhomogeneous regions in the aortic arch, either collagen-rich extremely thickened or collagen-poor hypotrophic regions. MFS animals treated with lipoic acid showed markedly reduced ROS production and lower ERK1/2 phosphorylation; meanwhile, aortic dilation and elastic fiber breakdown were unaltered. Of note, lipoic acid treatment associated with the absence of focal inhomogeneous regions in MFS animals. Losartan reduced aortic dilation and elastic fiber breakdown despite no change in ROS generation. In conclusion, oxidant generation by itself seems neutral with respect to aneurysm progression in MFS; however, lipoic acid-mediated reduction of inhomogeneous regions may potentially associate with less anisotropy and reduced chance of dissection/rupture.

The effect of lipoic acid in the prevention of myocardial infarction in diabetic rats.

We aimed to investigate the effect of lipoic acid in the prevention of myocardial infarction in diabetic rats. Rats were divided into five groups as control, ISO, LA+ISO, STZ+ISO and STZ+LA+ISO. To induce diabetes, single dose of streptozotocin was injected to STZ+ISO and STZ+LA+ISO groups. Lipoic acid (10 mg/kg/day) was injected for 14 days to LA+ISO and STZ+LA+ISO groups. To induce myocardial infarction, isoproterenol was injected to ISO, LA+ISO, STZ+ISO and STZ+LA+ISO groups on the days 13 and 14 of lipoic acid treatment. Cardiac necrosis and leucocyte infiltration were investigated histopathologically. Serum malondialdehyde levels, paraoxonase and lactonase activities were measured spectrophotometrically. Isoproterenol caused a significant increase in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation whereas a significant decrease in serum paraoxonase and lactonase activities. In myocardial infarcted non-diabetic rats, while lipoic acid caused a significant decrease in cardiac necrosis, leucocyte infiltration and serum lipid peroxidation and a significant increase in serum paraoxonase and lactonase activities, it did not change these histopathologic or biochemical parameters in myocardial infarcted diabetic rats. Lipoic acid, at the dose of 10 mg/kg, is effective to prevent myocardial infarction in non-diabetic rats but it is insufficient in diabetic rats (Tab. 1, Fig. 2, Ref. 35).

Effects of lipoic acid on migration of human B cells and monocyte-enriched peripheral blood mononuclear cells in relapsing remitting multiple sclerosis

Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation and demyelination resulting in clinical disability. The rodent MS model suggests that infiltration of monocytes and B cells contributes to disease pathogenesis. Here, we compared the migratory capacity of human monocytes and B cells from healthy control (HC) and relapsing-remitting MS (RRMS) subjects, with or without lipoic acid (LA) treatment. Basal migration of monocyte-enriched PBMCs from RRMS subjects is significantly higher than HC PBMCs. LA treatment significantly inhibits monocyte and B cell migration in both cohorts, and may thus be therapeutically effective for treatment of MS.

Potential Therapeutic Effects of Lipoic Acid on Memory Deficits Related to Aging and Neurodegeneration.

The aging process comprises a series of organic alterations, affecting multiple systems, including the nervous system. Aging has been considered the main risk factor for the advance of neurodegenerative diseases, many of which are accompanied by cognitive impairment. Aged individuals show cognitive decline, which has been associated with oxidative stress, as well as mitochondrial, and consequently energetic failure. Lipoic acid (LA), a natural compound present in food and used as a dietary supplement, has been considered a promising agent for the treatment and/or prevention of neurodegenerative disorders. In spite of a number of preclinical studies showing beneficial effects of LA in memory functioning, and pointing to its neuroprotective potential effect, to date only a few studies have examined its effects in humans. Investigations performed in animal models of memory loss associated to aging and neurodegenerative disorders have shown that LA improves memory in a variety of behavioral paradigms. Moreover, cell and molecular mechanisms underlying LA effects have also been investigated. Accordingly, LA displays antioxidant, antiapoptotic, and anti-inflammatory properties in both in vivo and in vitro studies. In addition, it has been shown that LA reverses age-associated loss of neurotransmitters and their receptors, which can underlie its effects on cognitive functions. The present review article aimed at summarizing and discussing the main studies investigating the effects of LA on cognition as well as its cell and molecular effects, in order to improve the understanding of the therapeutic potential of LA on memory loss during aging and in patients suffering from neurodegenerative disorders, supporting the development of clinical trials with LA.

The effect of the new combined cream on the protein synthetic activity of cells on the model of the thermal skin damage in rats

Aim. To study the mechanisms of the reparative action of a new combined cream on the model of thermal burn injury in rats.Materials and methods. On the model of thermal burn in rats the reparative properties of the new combined cream under the conditional name “Dermalipoin” containing α-lipoic acid, urea, olive oil, tea tree oil, PEG-400 were studied. To determine the level of the protein synthetic activity of cells (epitheliocytes of the stratified squamous epithelium in the epidermis and cells of the fibroblast cell in the edges of healing of thermal damage) the content of ribonucleoproteins (RNP) in the cytoplasm and deoxyribonucleoproteins (DNP) in the nuclei of the cells was assessed by the cytometric method.Results and discussion. On the model of thermal burn in rats “Dermalipoin” cream showed a more active effect on reparative processes compared to the reference drugs – methyluracil ointment and “Titriol” gel. It indicates a significant increase in the protein synthetic function of epitheliocytes of the stratified squamous epithelium in the epidermis and cells of the fibroblastic series at the healing edges. The reparative activity of the cream was, first of all, provided by the presence of thiol (sulfhydryl) groups in the molecule of lipoic acid, giving it the properties of an antioxidant. The antioxidant effect of lipoic acid promotes more efficient DNA molecule reparation after damage as a result of the oxidative stress.Conclusions. “Dermalipoin” cream shows a marked reparative effect due to the increase of the protein synthetic activity and acceleration of reparation of DNA molecules of epithelial cells after damage; as a result, the process of healing burns accelerates.

Lipoic Acid Combined with Epalrestat versus Lipoic Acid in Treating Diabetic Peripheral Neuropathy:A Meta-analysis.

Objective To compare the clinical effectiveness of lipoic acid combined with epalrestat versus lipoic acid in treating diabetic peripheral neuropathy(DPN). Methods Randomized controlled trials(RCTs) and clinical controlled trials on lipoic acid versus epalrestat for DPN before February 2016 were searched through five databases:CNKI,CBM,VIP,Wanfang,and PubMed. The quality of the included trials were assessed using Cochrane software and Jadad scores. Data were analyzed with Review Manager 5.3 software. Results Nine studies were included in the analysis. Meta analysis showed that the lipoic aid monotherapy was significantly inferior to lipoic acid-epalerestat combination therapy [RR=0.58,95%Cl(0.47,0.71),P<0.00001]. Inferiority of the lipoic acid monotherapy was also shown in nerve conduction velocity with WMDs of-4.94 [95%Cl(-7.41,-2.46),P<0.0001] for median motor nerve conduction velocity(MNCV),-5.08 [95%Cl(-7.68,-2.49),P=0.0001] for peroneal MNCV,-4.24 [95%Cl(-6.20,-2.29),P<0.0001] for median sensory nerve conduction velocity(SNCV),and-3.66 [95%Cl(-5.02,-2.31),P<0.00001] for peroneal SNCV. Sensitivity analysis showed that the results were robust. However,the included trials were limited by simple design,few subjective indicators,and short follow-up time. Conclusions Lipoic acid combined with epalrestat is better than lipoic acid alone in the treatment of DPN,as well as the MNCV and SNCV of median or peroneal nerve. Due to the low quality of the included studies,high-quality RCTs are warranted to validate the results.

Effects of lipoic acid and n-3 long-chain polyunsaturated fatty acid on the liver ovariectomized rat model of menopause.

Bilateral ovariectomy is an experimental model used to analyse the effects of menopause and develop strategies to mitigate the deleterious effects of this condition. Supplementation of the diet with antioxidants has been used to reduce potential oxidative stress caused by menopause. The purpose of the study was to analyse the effects of α-lipoic acid (LA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), dietary supplementation on oxidative stress in the livers of ovariectomized rats. In this study, we evaluated the effect of dietary supplementation with LA, DHA and EPA for a period of 16 weeks on oestrogen levels and oxidative stress biomarkers in the livers of ovariectomized 25 three-month-old rats. Serum oestrogen levels were lower after ovariectomy but were not altered by dietary treatments. LA was capable of acting in the liver, recovering the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase, and reducing protein oxidative damage. Moreover, LA supplementation reduced nitrite and nitrate levels. DHA and EPA recovered the antioxidant activity of cytosolic and mitochondrial superoxide dismutase, decreasing protein oxidation. Protection against lipid oxidation differed between treatments. The DHA-treated group showed increased levels of the lipid peroxidation biomarker malondialdehyde compared to the ovariectomized group. However, malondialdehyde levels were not altered by EPA treatment. The results suggest that the antioxidant response varies among evaluated supplementations and all supplements were able to alter enzymatic and non-enzymatic antioxidants in the livers of ovariectomized rats. DHA presented the most evident antioxidant effect, decreasing protein and lipid damage.