Alpha-lipoic acid preserves uterine and ovarian integrity in streptozotocin-induced diabetic rats via modulation of TGF-β and HSP70 pathways

Background: It is well known that renal TGFβ expression is related to the development of diabetic nephropathy. Alpha-lipoic acid (ALA), a potent antioxidant and cofactor of mitochondrial respiratory enzymes, can improve the insulin resistance and the vascular endothelial dysfunction, and suppresses the development of diabetic vascular complications. This study was undertaken to investigate whether ALA could reduce urinary protein excretion and renal TGFβ protein expression in obese type 2 diabetes mellitus animal model, Otsuka Long-Evans Tokushima Fatty (OLETF) rat. Methods: Obese 30 male OLETF rats were randomly divided to 3 groups at the age of 30 weeks. The rats in the Control group fed normal rat chow while the rats in the ALA group were fed with rat chow containing ALA (0.5% of food weight). Ten rats in the Pair-fed group were fed with normal rat chow, but were given the same amount of food as consumed by the ALA group . During 5 weeks of ALA feeding, food intake and body weight were checked in metabolic chamber. Blood glucose levels, HbA1c and urinary protein excretion were measured at 30 weeks and 35 weeks of age, and renal TGFβ protein expression at 35 weeks of age was measured by Western blot and represented by relative unit (RU). Immunohistochemical staining for TGFβ protein in renal tissue was also examined at 35 weeks of age. Results: Food intake, body weight, blood glucose levels, HbA1c and urinary protein excretion among the Control, ALA and Pair-fed groups at 30 weeks of age were not different. At 35 weeks of age, food intake was significantly decreased in the ALA group than the Control g roup (Control group vs. ALA group, 27.7 ± 1.1 g/day vs. 22.4 ± 1.4 g/day, P < 0.001), and body weight was significantly decreased in the ALA group than the Control and Pair-fed groups (Control group: 694.4 ± 10.3 g, ALA group: 600.4 ± 7.4 g, Pair-fed group: 685.4 ± 11.6 g, P < 0.001). Blood glucose levels were significantly decreased in the ALA group than the Control and Pair-fed groups (Control group: 157.7 ± 4.6 mg/dL, ALA group: 130.7 ± 4.8 mg/dL, Pair-fed group: 153.7 ± 3.3 mg/dL, P < 0.001) although blood glucose levels from 30 weeks to 34 weeks of age and HbA1c at 35 weeks of age were not different among the groups. U rinary protein excretion and renal TGFβ protein expression were significantly decreased in the ALA group than the Control and Pair-fed groups (urinary protein excretion, Control group: 5.033 ± 0.254 mg/mgCr, ALA group: 3.633 ± 0.303 mg/mgCr,

Objective: We evaluated the ability of alpha lipoic acid (ALA) to affect on coronary instent restenosis (ISR) in a porcine model. Methods: In vitro experiment: We stimulated porcine VSMC using G-CSF in the presence or absence of ALA. Activation of Akt, vascular endothelial growth factor (VEGF), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT)-3 were determined using western blot. And also, cell proliferation and migration assay were determined. In vivo experiment:Balloon overdilation injuries were performed in 2 coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). 16 bare metal stents were implanted randomized two coronary arteries in 8 pigs. Group I was control stent group (n=8), Group II was ALA coated stent group (n=8). Follow-up coronary angiogram (CAG) and histopathologic assessment were performed at 4 weeks after stenting. Results: G-CSF increased the phosphorylation of ERK and STAT-3, but after pretreatment of ALA, the phosphorylation of ERK and STAT-3 were significantly reduced. On histopathologic analysis, injury score, internal elastic lamina(IEL) area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm2 in control group and 2.2±1.1 mm2 in ALA group (p&lt;0.001), and the histopathologic area of stenosis(AS) was 75.9±8.5 % in control group, 23.5±10.5 % in ALA group (p&lt;0.001). The injury score and IEL area were not significantly different between the two groups. The neointimal area was 7.4±1.1 mm2 in control group and 1.4±0.8 mm2 in ALA group (p&lt;0.001), and the AS was 77.6±10.9 % in control group, 15.6±7.6 % in ALA group (p&lt;0.001). The number of inflammatory cells within neointima was lower in ALA group (63.2±23.7 % vs. 17.6±11.6 %, p&lt;0.001). Conclusion: ALA inhibits the activation of ERK, STAT-3 and proliferation of VSMC. Both high dose of oral ALA and ALA coated stents inhibit neointimal hyperplasia in a porcine ISR model

BackgroundThis study aims to compare methylprednisolone frequently used in the therapeutic practices of corrosive esophagus burns, sucralfate, a protective material of mucosal surfaces, and alpha lipoic acid, the most potent antioxidant in a rat model.MethodsA total of 40 female Sprague-Dawley rats were used in this study. The rats were equally divided into control, alpha lipoic acid, methylprednisolone, and sucralfate groups (n=10). A corrosive esophagus burn was created by using 10% pH:12 sodium hydroxide. No treatment was applied to the control group, and each group was given their own treatment. The treatment was continued regularly until the eighth day, when they were sacrificed. The corrosive esophagus burn lines were removed and tissue sections were stained with hematoxylin and eosin.ResultsThe difference in ulceration in the group treated with alpha lipoic acid was significant, compared to the other groups. The most excellent complete epithelialization and complete re-epithelialization were observed in the alpha lipoic acid group. The difference between the groups was significant, with complete re-epithelialization being the lowest in the control and methylprednisolone groups (42.9% and 12.5%, respectively) and the highest in the alpha lipoic acid group (77.8%). In terms of ulceration and re-epithelialization, comparable values were found in the alpha lipoic acid group. The main difference was that the inflammation levels in the sucralfate group were lower and more favorable than the other groups in this period. The glutathione level was significantly higher in the alpha lipoic acid group and decreased the tissue hydroxyproline level.ConclusionAlpha lipoic acid reduces esophageal ulceration, severity and prevalence of inflammation, severity and prevalence of fibrosis, decreases tissue damage by increasing blood glutathione level, and also reduces stricture in corrosive esophagus burns in rats.

MP26-18 ALPHA LIPOIC ACID REDUCES STONE GROWTH FOR CYSTINURIA PATIENTS: RESULTS FROM A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL

Mechanisms of Heat Shock Protein Release.- Release of Heat Shock Proteins: Passive Versus Active Release Mechanisms.- Hsp70 Peptide Acting as a Danger Signal for Natural Killer (NK) Cells.- Mechanisms of Stress-Induced Cellular Hsp72 Release.- Roles of Extracellular Heat Shock Proteins: A New Sense of Danger.- Heat Shock Protein Binding and Receptor-Mediated Signaling.- Macrophages and the Stress Response.- Heat Shock Proteins and Scavenger Receptors.- The Inside Story: Anti-Inflammatory roles of HSF1 and heat shock proteins.- Interaction of Heat Shock Protein 60 with Innate Immune Cells.- Immune Responses Elicited by Heat Shock Proteins.- HSP-APC Interactions: Initiation of Immune Responses.- Extracellular Functions for an Intracellular Protein: GRP94/GP96 Interactions with the Mammalian Immune System.- Hsp-Induced Stimulation of Immune Responses.- The Role of Heat Shock Proteins in the Elicitation of Immune Responses.- Hsp70 Family Members, Danger Signals and Autoimmunity.- The Immune Response Under Stress: Class I HLA Presentation of Host-Derived Peptides.- Extracellular Hsp 72: A Double-Edged Sword for Host Defense.- HSP60: A Pleiotropic Immune Signal.- Antigen Processing, Presentation and Effect on Inflammation and Disease.- Impact of HSP-Chaperoned Peptides on the MHC Class II-Dependent Presentation and Activation of CD4+ T Cells in Regard of Allo- and Autoantigens.- Heat Shock Proteins are Targets for T Cell Regulation: How Microbial HSP Induce IL10 Producing Anti-Inflammatory T Cells.- The Pro- and Anti-Inflammatory Properties of the Stress Protein GP96.- Anti-Tumor Response and Heat Shock Proteins (HSP): A friend or Foe relationship?.- Heat Shock Proteins and the Resolution of Inflammation by Lymphocytes.

Ulcerative colitis is a chronic inflammatory disease affecting the gastrointestinal tract. In addition to treatments aimed at healing inflammation and tissue damage, addressing redox imbalance and mitochondrial dysfunction is crucial. The aim of the present study is to investigate the effects of Alpha-Lipoic Acid (ALA), either alone or in combination with mesalamine, on oxidative/nitrosative stress, mitochondrial dynamics, and histopathological changes in a rat model of ulcerative colitis. Rats were divided into Control (C), Ulcerative Colitis (UC), Mesalamine (M), ALA, and Mesalamine + Alpha-lipoic acid (M + ALA) groups. Colitis was induced by intrarectal administration of 4% acetic acid. The disease activity index was the highest in the UC group and the lowest in the M + ALA group among the treatment groups. Macroscopic scores in the UC, M, and ALA groups were significantly higher compared to the C group. The oxidative stress index was the highest in the UC group, with significantly elevated levels compared to the C, ALA, and M + ALA groups. The nitrotyrosine level was also highest in the UC group and significantly elevated compared to the C, M, ALA, and M + ALA groups. Dynamin-related protein 1, Mitofusin-2, and PTEN-induced putative kinase 1 proteins showed significant increases in the UC group compared to the C group. In contrast, these protein levels were significantly reduced in the M + ALA group compared to the UC group. Histopathological scoring in the UC group increased, and ALA administration significantly ameliorated these parameters. Our results indicate that ALA has beneficial effects on increased oxidative stress, impaired mitochondrial dynamics, and altered histopathological scores in the rat colitis model.

Water temperature is a major environmental factor affecting fish activity, physiology, behavior, and growth. Alpha lipoic acid (ALA) has garnered much attention lately as an aqua feed supplement because of its antioxidant effects. Thus, this study aimed to assess the effect of dietary ALA on performance, hematological and immunological indices, behavior and oxidative stress, apoptosis, and genetic inflammation in Oreochromis niloticus following 60 days of cold stress. Two hundred forty fish were divided into four groups (15 fish/replicate, N = 60 fish/group). The control (CNT) and ALA groups were reared at 25 °C and fed a basal diet without any supplementation or a basal diet containing 600 mg ALA/kg diet, respectively. The cold water-stressed group (CWS) and ALA + CWS groups were reared at 18 °C and fed basal and basal diets containing ALA, respectively. The results revealed that dietary ALA supplementation significantly improved feed utilization and growth in fish. ALA also mitigated CWS-induced microcytic hypochromic anemia and hyperlipidemia. Moreover, ALA supplementation considerably enhanced the antioxidant status and boosted intestinal α amylase, lipase, protease, and serum acetylcholinesterase activity of CWS-exposed fish. Besides, ALA supplementation significantly reversed CWS-induced upregulation of proinflammatory genes, pro-apoptotic genes, heat shock protein, and proliferating cell nuclear antigen or downregulation of superoxide dismutase and catalase gene expressions in liver and spleen tissues. Furthermore, ALA supplementation reduced CWS-induced histopathological alterations in fish liver, spleen, and intestine. We can conclude that ALA (600 mg/kg diet) could be recommended as an aqua feed supplement to boost growth, antioxidant capacity, and immunity and attenuate inflammatory and apoptotic reactions of fish reared under CWS-induced.

Aim of this study was to investigate the effects of lipoic acid on uterine wound healing by immunohistochemical and biochemical assay in a rat uterine horn model with full thickness injury. Thirty-two female Wistar albino rats were randomised into five groups: Control group, with no intervention; uterine scar group 15days (US15d), uterine scar group 15days+alpha lipoic acid (ALA) (US15d+ALA), uterine scar group 30days (US30d) and uterine scar group 30days+ALA (US30days+ALA). After uterine incision 100mg/kg of ALA was administered by oral gavage for either 15 or 30days. Vascular endothelial growth factor (VEGF) and alpha smooth muscle actin (α-SMA) distribution were evaluated by immunohistochemical methods in tissue and ELISA methods in tissue homogenate. The percentage of α-SMA positive area in US15d+ALA and US30d+ALA groups was significantly higher than US15 and US30d groups. The percentage of VEGF positive area in US15d+ALA group was significantly higher than US15d group and US30d+ALA group was significantly higher than US30d group. Biochemically, α-SMA was significantly higher in the US15d+ALA group when compared to US15d group and higher in US30d+ALA group when compared to US30d group. VEGF was significantly higher in US15d+ALA and US30d+ALA groups when compared to US15 and US30d groups. In conclusion, ALA was found to be effective in enhancing wound healing in uterine full thickness injury.

This study investigates whether daily supplementation of 120-150 mg of caffeine can relieve symptoms of Burning Mouth Syndrome (BMS) compared to alpha-lipoic acid (ALA) and a control group. In this randomised controlled trial, 118 BMS patients were divided into three groups: caffeine, ALA, and control. The caffeine group received 120-150 mg of caffeine daily, the ALA group received 200 mg of ALA three times daily, and the control group received no interventions. Symptom relief was assessed over 2 weeks using the Visual Analog Scale (VAS), with subgroup analyses based on symptom subtypes, disease duration, symptom sites, and characteristics. The VAS of BMS patients in the caffeine and ALA groups exhibited significant reductions (p < 0.0005). The caffeine group exhibited a 65.1% symptom relief rate compared to 46.5% in the ALA group and 12.5% in the control group. Significant differences in symptom relief were noted between the caffeine and control groups (p < 0.0005) and between the ALA and control groups (p = 0.0032). No significant difference was observed between the caffeine and ALA groups (p = 0.084). Type I BMS patients in the caffeine group showed greater symptom relief than those in the ALA group (p = 0.026). Both caffeine and ALA effectively treated BMS, with caffeine showing higher efficacy in Type I patients. Treatments were well-tolerated with minimal adverse effects, suggesting caffeine and ALA as promising treatments for BMS, warranting further research on their long-term effects and mechanisms of action. [The study was registered on ClinicalTrials.gov (Identification No. NCT06195137).].

The purpose of this study is to characterize resistance mechanisms of non-small cell lung cancer (NSCLC) to heat shock protein 90 (HSP90) inhibition. Unexpectedly, we identified anti-Mullerian hormone (AMH) and its type II receptor (AMHR2) as two resistance associated genes. AMH and AMHR2 are TGF-ß/BMP superfamily members that share common type I receptors with BMP, resulting in overlapping signaling outputs. AMH and AMHR2 have thus far predominantly been studied in the context of gonadal development, in regulation of the female reproductive cycle and in gynecological malignancies, and AMH is not known to be expressed outside of these tissues. Using a focused RNAi library designed to detect genes associated with resistance to the HSP90 inhibitor ganetespib, siRNAs against AMH and AMHR2 sensitized 4 out of 5 and 3 out of 5 NSCLC cell lines to ganetespib, respectively. We then for the first time confirmed expression of AMH and AMHR2 in this non-gonadal tumor environment. Furthermore, analysis of data from The Cancer Genome Atlas (TCGA) indicated that AMH and AMHR2 are significantly upregulated in a subpopulation of NSCLC. Strikingly, depletion of AMH/AMHR2 induced EMT-like features, including downregulation of cadherins, a mesenchymal morphology, increased invasion, and expression of mesenchymal markers: features that are generally associated with resistance to chemotherapy. In contrast, inhibition of HSP90 selected for a more epithelial-like population of cells, as evident by increased E-cadherin or P-cadherin, and downregulation of mesenchymal markers such as VIM and ZEB1. To confirm that mesenchymal-like cells are indeed more responsive to HSP90 inhibition, we depleted E-cadherin or P-cadherin and again observed sensitization to ganetespib. We further found that AMH and AMHR2 did not confer sensitization to cisplatin. Interestingly, depletion of cadherins, and the associated induction of EMT-like properties, also resulted in downregulation of AMH and AMHR2, further supporting the link between AMH/AMHR2 expression and epithelial identity. In vivo studies confirmed that AMH depletion sensitizes NSCLC cells to ganetespib and showed that it also significantly reduces overall tumor volume. Reduction of AMH or AMHR2 also decreased phosphorylation of direct effector SMAD proteins, and depressed activity of NFκB and AKT, both regulators of EMT and survival. These results for the first time indicate the presence of an AMH-AMHR2-NFκB-AKT signaling axis of therapeutic relevance in NSCLC. To further explore the therapeutic potential of this observation, we treated NSCLC with combinations of ganetespib and the proteasome inhibitor bortezomib- an inhibitor previously shown to disrupt NFκB signaling in some cancers - and observed significant synergy between the two drugs. In conclusion, our work for the first time characterizes AMH and AMHR2 in NSCLC. We go on to show that AMH and AMHR2 regulated canonical-SMAD signaling as well as non-canonical AKT-NFκB signaling, in addition to regulating the epithelial identify of cancer cells. Importantly, our results also suggest that AMH and AMHR2 may serve as biomarkers to predict resistance to HSP90 inhibitors, and that it may be beneficial to prime lung tumors with HSP90 inhibitors, to reverse EMT and decrease survival signaling, prior to treatment with chemotherapy. Note: This abstract was not presented at the conference. Citation Format: Tim N. Beck, Vladislav Korobeynikov, Alexander Kudinov, Rachel Georgeopoulos, Emmanuelle Nicolas, Margret B. Einarson, Yan Zhou, Yanis Boumber, David A. Proia, Ilya G. Serebriiskii, Erica A. Golemis. Anti-Mullerian hormone (AMH) supports epithelial identity and survival signaling in lung cancer. [abstract]. In: Proceedings of the Fourth AACR International Conference on Frontiers in Basic Cancer Research; 2015 Oct 23-26; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2016;76(3 Suppl):Abstract nr B25.

In this research, it has been aimed to evaluate the improvement effects of alpha lipoic acid (ALA), ascorbic acid-6-palmitate (AA6P), fish oil (FO), and their combination (COM) on some biochemical properties in erythrocytes of streptozotocin (STZ)-induced diabetic male rats. According to experimental results, glutathione (GSH) level in erythrocytes decreased in diabetes (P < 0.01), D + ALA, and D + AA6P groups (P < 0.001). Malonaldehyde (MA) level increased in diabetes (P < 0.05), D + FO, and D + COM groups (P < 0.001), but its level in D + AA6P and D + ALA groups was lower in diabetes group (P < 0.01). Total lipid level in diabetes and diabetes plus antioxidant administered groups were higher than control. Total cholesterol level was high in diabetes and D + ALA groups (P < 0.05), but its level reduced in D + FO compared to control and diabetes groups, P < 0.05, < 0.001, respectively. Total triglyceride (TTG) level was high in the D + ALA (P < 0.05) and D + COM (P < 0.001) groups. In contrast, TTG level in blood of diabetes group was higher than diabetes plus antioxidant and FO administered groups (P < 0.001). According to gas chromatography analysis results, while the palmitic acid raised in diabetes group (P < 0.05), stearic acid in D + FO, D + ALA, and diabetes groups was lower than control (P < 0.05), oleic acid reduced in D + COM and D + FO groups, but its level raised in D + AA6P and D + ALA groups (P < 0.01). As the linoleic acid (LA) elevated in ALA + D, D + AA6P, and diabetes groups, linolenic acid level in diabetes, D + AA6P, and D + FO groups was lower than control (P < 0.001). Arachidonic acid (AA) decreased in D + ALA, D+ AA6P, and diabetes groups (P < 0.01), but its level in D + COM and D + FO was higher than control (P < 0.05). Docosahexaenoic acid (DHA) increased in D + AA6P and D + COM (P < 0.05). While the total saturated fatty acid level raised in diabetes group, its level reduced in D + ALA and D + FO groups (P < 0.05). In contrast, total unsaturated fatty acid level in D + ALA and D + FO groups was higher than control (P < 0.05). In conclusion, present data have confirmed that the combination of the ALA, AA6P, and FO have improvement effects on the recycling of GSSG to reduced GSH in erythrocytes of diabetic rats, and in addition to this, oxidative stress was suppressed by ALA and AA6P, and unsaturated fatty acid degree was raised by the effects of ALA and FO.

Background and Objectives:Alpha lipoic acid (ALA) is beneficial for improving endothelial dysfunction and preventing atherosclerosis-related diseases. We evaluated the affect of ALA on stent restenosis in a porcine model. Materials and Methods:The First experiment: Balloon overdilation injuries were performed in two coronary arteries in 12 pigs. Four weeks after the balloon overdilation injury, 24 bare metal stents were placed for 24 injured coronary arteries. We randomized into two groups (12 stents per group; control group: aspirin and clopidogrel only, ALA group: aspirin and clopidogrel plus 100 mg/kg ALA during 4 weeks). The Second experiment: Stents were randomly implanted in 2 coronary arteries in 8 pigs. Group I was the control stent group (n=8), and group II was the ALA coated stent group (n=8). Follow-up coronary angiogram and histopathologic assessment were performed at 4 weeks after stenting in both experiments. Results:The First experiment On histopathologic analysis, the injury score and internal elastic lamina area did not differ significantly between the two groups. The neointimal area was 7.3±0.9 mm in the control group and 2.2±1.1 mm in the ALA group (p<0.001), and the histopathologic area of stenosis was 75.9±8.5% in the control group and 23.5±10.5% in the ALA group (p<0.001). The Second experiment: The injury score and internal elastic lamina area were not significantly different between the two groups. The neointimal area was 7.4±1.1 mm in the control group and 1.4±0.8 mm in the ALA group (p<0.001), and the histopathologic area of stenosis was 77.6±10.9% in the control group and 15.6±7.6% in the ALA group (p<0.001). Conclusion:Both a high dose of oral ALA and ALA coated stents inhibited neointimal hyperplasia in this porcine coronary artery stent restenosis model. (Korean Circulation J 2006;36:495-502)

To determine whether the possible oxidative effect of methotrexate (Mtx) on ovary and to evaluate the effectiveness of alpha lipoic acid (ALA), which may be useful in many oxidative stress models.Thirty-two female Wistar-albino rats were randomly divided into four groups; control group, alpha lipoic acid group (ALA 100 mg/kg, 10 days), multiple dose Mtx group (Mtx 1 mg/kg 1, 3, 5, 7 days) and Mtx and ALA group (Mtx 1 mg/kg 1, 3, 5, 7 days and ALA 100 mg/kg, 10 days). Serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI), tumor necrosis factor-alpha (TNF-α), tissue malondialdehyde (MDA) and activities of glutathione peroxidase (GSH-Px) and catalase (CAT) and anti-Mullerian hormone (AMH) and total ovarian follicle count were evaluated.Mtx administration caused a significant decrease in TAS, a significant increase in TOS and OSI, a significant increase in MDA levels and a decrease in GSH-Px and CAT activity. Moreover the proinflammatory cytokine (TNF-α) was increased in the Mtx group. And AMH values and total follicle count were significantly decreased in Mtx group. However, ALA treatment reversed biochemical results and AMH levels and total follicle count.Alpha lipoic acid ameliorates methotrexate induced oxidative damage of ovarian in rats.

As obligate parasites, malaria parasites have developed mechanisms for survival under unfavourable conditions in host cells. The chapters in this book have extensively discussed the evidence that heat shock proteins of malaria play a key role in parasite survival in host cells. The role of the heat shock protein arsenal of the parasite is not limited to the protection of the parasite cell, as some of these proteins also promote the pathological development of malaria. This is largely due to the export of a large number of these proteins to the infected erythrocyte cytosol. Although PfEMP1 is the main virulent factor for the malaria parasite, some of the exported malarial heat shock proteins appear to augment parasite virulence (Maier et al. 2008). While this book largely delves into experimentally validated information on the role of heat shock proteins in the development and pathogenicity of malaria, some of the information is is based on hypotheses yet to be fully tested. Therefore, it is important to highlight what we know to be definite roles of malarial heat shock proteins. This will help us distill information that could provide practical insights on the options available for future research directions, including interventions against malaria that may target the role of heat shock proteins in the development of the disease.

Objective:Radiation is used to treat cancer but causes serious complications, such as liver toxicity. In this study, the protective effects of alpha lipoic acid against the unwanted effects of radiation used in many cancer treatments which can cause damage after treatment were investigated.Material and Methods:The sample consisted of 32 Sprague–Dawley male rats randomized equally into 4 groups. The control group received no intervention. The alpha lipoic acid group was administered 50 mg/kg (dissolved in 0.9% NaCl) for 3 days. The ionizing radiation group was exposed to a total of 30 Gy radiation in 10 Gy fractions per day. The ionizing radiation + alpha lipoic acid group was administered 50 mg/kg alpha lipoic acid® prior to exposure to a total of 30 Gy radiation in 10 Gy fractions per day. Rats were sacrificed by cervical dislocation, and the liver was removed for histopathological studies and superoxide dismutase and malondialdehyde assays. Liver tissues were histopathologically assessed using hematoxylin-eosin staining after 4 weeks of the experiment.Results:The ionizing radiation + alpha lipoic acid group had significantly less severe necrosis than the ionizing radiation group. Compared to the ionizing radiation group and the ionizing radiation + alpha lipoic acid group, superoxide dismutase enzyme activity was decreased with the addition of alpha lipoic acid. In addition, when the amount of malondialdehyde, which is a marker of oxidative stress, was examined, it was determined that the amount of malondialdehyde in the ionizing radiation + alpha lipoic acid group was lower than in the ionizing radiation Group.Conclusion:Alpha lipoic acid® mitigates radiotherapy-induced damage in liver tissue.