Protective Effect Of Alpha-lipoic Acid Research Articles

Protective effects of alpha-lipoic acid and alagebrium chloride against testicular dysfunction induced by varicocele and advanced glycation end (AGE) – Rich diet in a rat mode

Heat stress from varicocele can heighten oxidative stress in the testes, impacting sperm function and male fertility. Antioxidant therapy is explored as a remedy for varicocele, while dietary factors like processed foods, sugar, and saturated fats correlate with male infertility. Advanced glycation end products (AGEs), generated through glycation processes, can provoke oxidative stress, inflammation, and adverse health consequences. Alpha-lipoic acid (ALA), a versatile antioxidant, may alleviate oxidative stress and counteract the impact of AGEs, potentially by enhancing glucose reabsorption. Alagebrium chloride (ALT711), an anti-AGE compound, exhibits promise in cardiovascular disease by disrupting AGE cross-links. This study investigates the effects of ALA and ALT-711 on testicular function in varicocele and AGEs animal models. Both AGE and varicocele were found to alter the natural trends, leading to abnormal patterns in sperm parameters, testicular functional tests, as well as the expression of CML, RAGE, and TNF-α proteins. However, the administration of ALA or ALT711 helped mitigate these effects. While ALA demonstrated a slightly greater overall benefit compared to ALT, the difference was not statistically significant.

Evaluating the protective effect of alpha-lipoic acid against gentamicin-induced gonadal toxicity indicated by histopathology.

Gentamicin induces gonadotoxicity in animal models, accompanied by oxidative stress. This study evaluated the histopathological protective effect of alpha-lipoic acid against gentamicin-induced gonadotoxicity. A parallel experimental study included 50 albino Wister rats, which were divided into 5 groups of ten according to the intraperitoneal intervention: group I received gentamicin, group II received gentamicin plus alpha-lipoic (100 mg/kg), group III received gentamicin plus a double dose of alpha-lipoic acid, group III received gentamicin plus oral vitamin E, and group IV received NaCl 0.9% (control). The animals were equally euthanized on days 15 and 16. Tests were dissected, prepared, and stained using a light microscope for histopathological examination. Rats exposed to gentamicin showed degeneration of seminiferous tubules, characterized by a significant decrease in germinal epithelial cells, impaired spermatogenesis, and a lack of spermatozoa in the lumen. An improvement in testes of animals co-treated with alpha-lipoic acid or vitamin E, including restoration of spermatogenesis and epithelial thickness. The histometric analysis also showed that the tubule epithelial thickness decreased when gentamicin was used, but this did not happen when alpha-lipoic acid or vitamin E was added simultaneously. The detrimental effects of gentamicin on testicular architecture are preventable through alpha-lipoic acid or vitamin E co-treatment. Keywords: Alpha-lipoic acid; Gonads; Histometric; Gentamicin; Seminiferous tubule; Spermatogenesis.

Phytochemical analysis underlying membrane stabilization and anti-oxidant promising potentials of Acacia nilotica seed extract

This study has aimed to evaluate the Acacia nilotica seed extract as a natural antioxidant and membrane stabilizer, as well as screening phytochemicals contained in the extract that may underline these activities. Antioxidant activity was evaluated using Phospho-molybdenum and DPPH antioxidant assays; membrane stabilization was evaluated using HRBC-MS assay, whereas phytochemicals were detected using qualitative analytical tests. Acacia nilotica hydro-methanolic extract exhibited potent, concentration (4-512 μg/mL)-dependent antioxidant activity indicated by Phospho-molybdenum and DPPH antioxidant assays, with IC50 values of 100.5 and 33.19 μg/mL, respectively. In addition, the extract exerted membrane stabilizing effects in a concentration (4-512 μg/mL)-dependent manner, with an IC50 value of 41.47 μg/mL. Phytochemical analysis of the plant extract clarified the active biological constituent(s) underlying these effects, including tannins, saponins, gums, flavonoids, anthraquinone glycosides, carbohydrates and proteins. These data may suggest Acacia nilotica extract, according to in vitro assays, as a highly potent antioxidant and membrane stabilizer derived from nature and could be applied as an adjunct therapy in disease conditions associated with inflammation and oxidative stress. Keywords: Acacia nilotica; antioxidant; membrane stabilizer; anti-inflammatory.

Protective Effects of Alpha-lipoic Acid, Resveratrol, and Apigenin Against Oxidative Damages, Histopathological Changes, and Mortality Induced by Lung Irradiation in Rats.

This study investigated the protective effects of three antioxidants on radiationinduced lung injury. Oxidative stress is one of the key outcomes of radiotherapy in normal tissues. It can induce severe injuries in lung tissue, which may lead to pneumonitis and fibrosis. Recently, interest in natural chemicals as possible radioprotectors has increased due to their reduced toxicity, cheaper price, and other advantages. The present study was undertaken to evaluate the radioprotective effect of Alpha-lipoic Acid (LA), Resveratrol (RVT), and Apigenin (APG) against histopathological changes and oxidative damage and survival induced by ionizing radiation (IR) in the lung tissues of rats. First, the lung tissue of 50 mature male Wistar rats underwent an 18 Gy gamma irradiation. Next, the rats were sacrificed and transverse sections were obtained from the lung tissues and stained with hematoxylin and eosin (H and E) and Mason trichrome (MTC) for histopathological evaluation. Then, the activity of Glutathione peroxidase (GPx), Superoxide Dismutase (SOD), and Malondialdehyde (MDA) was measured by an ELISA reader at 340, 405, and 550 nm. Based on the results of this study, IR led to a remarkable increase in morphological changes in the lung. However, APG, RVT, and LA could ameliorate the deleterious effects of IR in lung tissue. IR causes an increase in GPX level, and APG+IR administration causes a decrease in the level of GPX compared to the control group. Also, the results of this study showed that RVT has significant effects in reducing MDA levels in the short term. In addition, compared to the control group, IR and RVT+IR decrease the activity of SOD in the long term in the lung tissues of rats. Also, the analysis of results showed that weight changes in IR, LA+IR, APG+IR, and control groups were statistically significant. APG and RVT could prevent tissue damage induced by radiation effects in rat lung tissues. Hence, APG, LA, and RVT could provide a novel preventive action with their potential antioxidant anti-inflammatory properties, as well as their great safety characteristic.

Protective effect of alpha-lipoic acid and epalrestat on oxaliplatin-induced peripheral neuropathy in zebrafish.

Oxaliplatin is a platinum-based anti-cancer drug widely used in colorectal cancer patients, but it may cause peripheral neuropathy. As one of the main causes of oxaliplatin-induced peripheral neuropathy (OPN) is oxidative stress, which is also a key factor causing diabetic peripheral neuropathy (DPN), the aim of this study was to evaluate the preventive effects of alpha-lipoic acid (ALA) and epalrestat (EP), which are used for the treatment of DPN, in an OPN zebrafish model. Tg(nbt:dsred) transgenic zebrafish, with sensory nerves in the peripheral lateral line, were treated with oxaliplatin, oxaliplatin/EP, and oxaliplatin/ALA for 4 days. A confocal microscope was used to visualize and quantify the number of axon bifurcations in the distal nerve ending. To analyze the formation of synapses on sensory nerve terminals, quantification of membrane-associated guanylate kinase (MAGUK) puncta was performed using immunohistochemistry. The number of axon bifurcations and intensity of MAGUK puncta were significantly reduced in the oxaliplatin-treated group compared with those in the embryo medium-treated group. In both the oxaliplatin/EP and oxaliplatin/ALA-treated groups, the number of axon bifurcations and intensity of MAGUK puncta were greater than those in the oxaliplatin-treated group (p < .0001), and no significant difference was observed between larvae treated with oxaliplatin/ALA 1 μM and oxaliplatin/EP 1 μM (p = .4292). ALA and EP have protective effects against OPN in zebrafish. Our findings show that ALA and EP can facilitate more beneficial treatment for OPN.

Alpha Lipoic Acid Protects Human SH-SY5Y Cells Against Quinolinic Acid-Induced Toxicity: Focusing on ROS Levels and Cell Cycle

Objectives: An abnormal buildup of Quinolinic Acid (QuA) is usually linked to the death of nerve cells and a condition known as neuritis in various forms of neurodegenerative illness. Alpha Lipoic Acid (ALA) has substantial antioxidant properties, according to previous studies. However, the protective effects of ALA against the neurotoxicity induced by QuA are unknown. This work aimed to determine whether ALA could shield the SH-SY5Y neuroblastoma cell line from QuA-induced neurotoxicity.&#x0D; Methods: Cell viability was assessed using the MTT assay, while cell cycle and apoptotic effects were evaluated using flow cytometry. Cellular levels of reactive oxygen species (ROS) were also examined.&#x0D; Results: The findings showed that ALA, at non-toxic concentrations, had a protective effect against QuA-induced toxicity. Moreover, pretreatment with ALA reduced the number of cells that underwent apoptosis. Also, it was found that the percentage of apoptotic cells (i.e., those in the sub-G1 phase) was considerably increased following QuA therapy. ALA also dramatically reduced the production of ROS by QuA.&#x0D; Conclusion: The results suggest that ALA appears to be an effective neuroprotectant and antioxidant against QuA-induced neurotoxicity.

Protective effects of alpha-lipoic acid on anxiety-like behavior, memory and prevention of hippocampal oxidative stress in methamphetamine-treated rats.

Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. Wistar male rats (200-220g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10mg/kg, and (5) methamphetamine + alpha-lipoic acid 40mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20mg/kg, 2h interval). Alpha-lipoic acid was injected 30min, 24h, and 48h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property.

Nrf2-mediated protective effect of alpha-lipoic acid on synaptic oxidative damage and inhibition of PKC/ERK/CREB pathway in bisphenol A-exposed HT-22 cells

The harmful effects of bisphenol A (BPA) on learning and memory may involve hippocampal oxidative damage; however, the underlying mechanism remains unclear. Antioxidants that antagonize BPA-induced neuronal oxidative damage lack research. This study aimed to develop an in vitro model using the HT-22 mouse hippocampal neuronal cell line to investigate the neurotoxic mechanism of BPA and the protective effect of alpha-lipoic acid (ALA) on nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition. The results showed that ALA reduced BPA-induced reactive oxygen species and neuronal nitric oxide synthase (nNOS) levels; however, inhibiting Nrf2 weakened the protective effects of ALA. BPA reduced mitochondrial complex I/III activity and ATP levels, but ALA ameliorated this damage. ALA improved the BPA-induced downregulation of the kelch-like ECH-associated protein 1 (keap1)/Nrf2 system, synaptic-related proteins, and the protein kinase C (PKC)/extracellular signal-regulated kinase (ERK)/cAMP response element binding protein (CREB) pathway; however, the protective effects of ALA were weakened when Nrf2 was inhibited. Our results suggest that BPA causes oxidative damage to HT-22 cells by damaging mitochondrial function, nNOS, and the keap1/Nrf2 system, thereby impairing synaptic-related proteins and the PKC/ERK/CREB pathway. ALA counters BPA-induced damage via Nrf2, which may be a significant target for the protective action of ALA.

The effect of alpha-lipoic acid on oxidative parameters, SCUBE-1 and SCUBE-2 in hepatic ischemia-reperfusion injury in cholestatic rats.

The aim of the study was to evaluate the protective effects of alpha-lipoic acid (ALA) on the liver, oxidative parameters, and signal peptide-CUB-epidermal growth factor-like domain-containing proteins 1 and 2 (SCUBE-1 and -2) in an experimental cholestatic hepatic ischemia-reperfusion (IR) model. Twenty-four female rats were included in the study and divided into four groups of six rats each. Group 1 was the control group, in which only laparotomy was performed; Group 2 underwent laparotomy and received alpha-lipoic acid (ALA) on a daily basis; bile duct ligation was performed in Group 3; bile duct ligation was performed, and ALA was administered to Group 4. All rats underwent relaparotomy on the seventh day, followed by 30 minutes of hepatic ischemia and 60 minutes of reperfusion in Groups 3 and 4. Liver tissue and blood samples were taken for histopathological and biochemical examinations. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), direct bilirubin (DBIL), albumin, ischemia modified albumin (IMA), SCUBE-1, SCUBE-2, total antioxidant status (TAS) and total oxidant status (TOS) levels were also examined. The SCUBE-1 and SCUBE-2 values in Group 4 were lower than in Group 3, but no significant difference was observed between all the groups. The AST, TBIL, and DBIL levels were significantly higher in Groups 3 and 4 than in Groups 1 and 2 (p<0.0001). Although TOS was the highest in Group 3, the measurements were similar across the groups (p=0.464). IMA and TAS were similar between Groups 3 and 4 but significantly higher in these groups than in Groups 1 and 2 (p=0.001). The hepatic injury observed in Groups 3 and 4 was significantly higher than that observed in Groups 1 and 2 (p<0.0001). In the histopathological examination, neutrophilic infiltration and bile duct proliferation were less commonly detected in the portal areas in Group 4 than in Group 3, and necrotic foci were not observed due to the administration of ALA. The promising effects of ALA, known for its powerful antioxidant properties, on the IR injury of the liver can allow it to enter clinical practice in the future.

The Protective Effect of Alpha-Lipoic Acid on Oxidative Stress and Proinflammatory cytokines in L-Arginine-Induced Acute Pancreatitis Male Rats

Acute pancreatitis (AP) is a common serious stirring disease of the pancreas characterized by strict abdominal twinge that lasts for days to weeks. Rats were injected with high dose of the amino acid L-arginine (500 mg/kg B.W.). The study has been done to induce acute pancreatitis (AP) by L-Arginine (Arg) and to investigate the effect of AP on body weight, body weight gain, serum amylase, lipase, oxidative stress and proinflammatory cytokine parameters. In addition, some histopathological changes in pancreas and intestine were examination in male rats. Serum amylase, lipase, IL-6, and TNF-α levels, and MDA levels significantly increased in rats with L-Arginine induced AP. However, the boy weight and body weight gain, serum GPx, SOD and CAT activity significantly reduced. In addition, some histological changes in pancreas and intestine were identified, reversed and improved with ALA treatment.

Alpha-lipoic acid protects against aortic aneurysm and dissection by improving vascular smooth muscle cell function

Alpha-Lipoic acid (ALA) plays a protective role in a variety of vascular diseases, however, its effect on aortic aneurysm and dissection (AAD) has not been reported. In this study, we found that Alpha-Lipoic Acid treatment significantly improved the AAD and AAA development, which was demonstrated by ameliorated aneurysmal dilation, decreased aortic dissection and aneurysm incidence, improved aortic morphology and inhibited elastin degradation. ALA blunted extra-cellular matrix degradation, vascular smooth muscle cell (VSMC) loss and phenotype transformation. Moreover, the protective effect of ALA on VSMCs may be related to the amelioration of mitochondrial dysfunction. In conclusion, our study revealed that ALA exerts inhibitory effects against progression of AAD, thus suggesting that ALA may be a novel therapeutic molecule for AAD.

Protective Effects of Alpha-Lipoic Acid against 5-Fluorouracil-Induced Gastrointestinal Mucositis in Rats.

Alpha-lipoic acid (ALA) is extensively utilized in multivitamin formulas and anti-aging products. The purpose of this study was to investigate the potential protective benefits of ALA on 5-fluorouracil (5-FU)-induced gastrointestinal mucositis in Wistar albino rats. Tissues from the stomach, small intestine, and large intestine were excised, and blood sera were obtained to identify biochemical indices such as TNF-α, IL-1β, MDA, GPx, SOD, MMP-1, -2, -8, and TIMP-1. A histopathological study was also performed. The results revealed mucositis-elevated TNF-, IL-1, MDA, MMP-1, -2, -8, and TIMP-1 levels in both tissues and sera, and these values dropped dramatically following ALA treatment. Reduced SOD and GPx activities in mucositis groups were reversed in ALA-treated groups. The damage produced by mucositis in the stomach and small intestine regressed in the ALA-treated group, according to histopathological evaluation. Consequently, the implementation of ALA supplementation in 5-FU therapy may act as a protective intervention for cancer patients with gastrointestinal mucositis. In light of the findings, ALA, a food-derived antioxidant with pleiotropic properties, may be an effective treatment for 5-FU-induced gastrointestinal mucositus, and prevent oxidative stress, inflammation, and tissue damage in cancer patients receiving 5-FU therapy.

Alpha-Lipoic Acid Protects Against Doxorubicin-Induced Cardiotoxicity by Regulating Pyruvate Dehydrogenase Kinase 4.

As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism.

Alpha-lipoic acid-role in improving both reserpine toxicity and paroxetine treatment in the cerebral cortex of albino rats; histological, ultrastructural, immunohistohemical and biochemical studies

BackgroundReserpine is a monoamine depletory drug cause oxidative damage and used to induce depression-like features in rodent model. Paroxetine is an antidepressant drug that exerts its effects by inhibiting dopaminergic neurons although it may exert much pathological damage. Alpha-lipoic acid (ALA) is an endogenous antioxidant co-factor of important enzymatic complexes. The present study was aimed to elucidate the possible protective effect of ALA in the improvement of the deleterious cerebral cortex injury after reserpine and paroxetine treatment. Forty adult male albino rats were equally divided into 5 groups. Group I served as control group orally treated with saline solution all the experiment period. Group II animals orally treated with ALA (200 mg/kg/day) for six weeks. The induction of depression-like features occurred when the rest of animals were intraperitoneally treated with 25 mg/kg of reserpine once daily for consecutive 14 day. Then these animals were divided into; Group III (reserpine group) animals in this group were sacrificed on 15th day. Group IV; reserpine-treated animals were treated with paroxetine (20 mg/kg) daily for 6 weeks. Group V, animals in this group were received paroxetine and ALA daily for 6 weeks.ResultsReserpine-treated rats showed disorganized layers of cerebral cortex with degenerative, apoptotic and necrotic changes. Ultrastructure changes include both pyramidal and granule cells with severe degenerative, necrotic and apoptotic features. The nuclei appeared pyknotic; irregular with chromatin condensation as well as the cytoplasm of these cells contained many degenerated organelles. In addition, a significant increase in total oxidative stress and decrease in total antioxidant capacity, norepinephrine, dopamine and serotonin levels were recorded. The same treatment showed significant decrease in proliferating cell nuclear antigen (PCNA) expression and significant increase in caspase-3 expression in the granule and pyramidal cells. After paroxetine-treatment these parameters were more or less similar to those observed in reserpine-treated ones. While an obvious improvement was appeared when animal treated with both paroxetine and ALA and; all parameters restored its normal features.ConclusionsThis study concluded that; ALA treatment attenuated the cerebral injury induced by reserpine and improved the effects of paroxetine in rats due to its anti-inflammatory, anti-apoptotic and antioxidant activities.

Protective effects of alpha-lipoic acid on bleomycin-induced skin fibrosis through the repression of NADPH Oxidase 4 and TGF-β1/Smad3 signaling pathways.

The aim of this study was to determine the protective effects of alpha-lipoic acid (ALA), which is known as a powerful antioxidant, and the possible related molecular mechanisms that mediate its favorable action on skin fibrosis in the bleomycin (BLM)-induced scleroderma (SSc) model in mice. The experimental design was established with four groups of eight mice: Control, ALA (100mg/kg), BLM (5μg/kg), and BLM + ALA group. BLM was administered via subcutaneous (sc) once a day while ALA was injected intraperitoneally (ip) twice a week for 21 days. Histopathological and biochemical analyses showed that ALA significantly reduced BLM-induced dermal thickness, inflammation score, and mRNA expression of tumor necrosis factor-alpha (TNF-α) in the skin. Besides, the mRNA expressions of the subunits of NADPH oxidase, which are Nox4 and p22phox, were found to be significantly induced in the BLM group. However, ALA significantly reduced their mRNA expression, which were in parallel to its decreasing effect on serum total oxidant status (TOS) level. Moreover, it was found that ALA downregulated the mRNA expressions of alpha-smooth muscle actin (α-SMA), collagen type I and fibronectin in the skin tissue of the BLM group. Additionally, it was shown that ALA reduced significantly the TGF-β1 and p-Smad3 protein expressions in the BLM + ALA group. On the other hand, ALA did not exhibit any significant effect on the p38 mitogen-activated kinase (MAPK) activation induced by BLM. All these findings point out that ALA may be a promising treatment for the attenuation of skin fibrosis in SSc patients.

Evaluation of the effects of donepezil, memantine and α-lipoic acid combined administration in amnesia rats on impaired cognitive functions in terms of behavioural, apoptotic, cholinergic and glutamatergic systems

Objective: The aim of the study was to evaluate the possible protective effects of alpha-lipoic acid (α-LA), donepezil and memantine combined therapy in the scopolamine-induced amnesia rat model. &#x0D; Objective: The aim of the study was to evaluate the possible protective effect of donepezil, memantine and alpha-lipoic acid (α-LA) combined therapy in the scopolamine-induced amnesia rat model. &#x0D; Methods: In this study, the effect of combined therapy used in the treatment of scopolamine-induced amnesia on behavioural parameters was evaluated using Y-maze and new object recognition (NOR) test. In addition, muscarinic acetylcholine receptor subtype M1, N-methyl-D-aspartate receptor NR2B subunit, brain-derived neurotrophic factor (BDNF) and mitochondrial apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) / Bcl-2 associated X (Bax) ratio, caspase (casp) -3, and -9] expression levels were evaluated using the western blot method in the frontal cortex and hippocampus regions. &#x0D; Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NOR test were reversed with the combined treatment of memantine, donepezil and α-LA. According to immunoblotting results in both brain regions, scopolamine-induced decreased M1, BDNF, Bcl-2 / Bax ratio and increased NR2B, casp-3 and -9 expression levels were found to be reversed to almost control values with combined treatment. &#x0D; Conclusion: Consistent with the literature, our study results suggest that the positive contribution of α-LA to the combined treatment of donepezil and memantine, which is used in the routine treatment of neurodegenerative diseases, may be a treatment option in the future.&#x0D; Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NORT test were reversed with the combined treatment of memantine, donepezil and α-LA. In addition, decreased BDNF, M1, bcl-2/bax ratio and increased NR2B, caspase-3 and caspase-9 expression levels due to scopolamine in both regions were improved with α-LA, donepezil and memantine combined therapy. &#x0D; Conclusion: The results of our study and other study results in the literature suggest that α-LA may be a future treatment option due to its positive contribution to the effects of other drugs used in the routine treatment of neurodegenerative diseases.

Protective effects of alpha-lipoic acid on hair cell damage in diabetic zebrafish model

Hearing impairment is one of the complications in diabetes mellitus; however, there are very few therapeutic studies on it. In this study, we investigated the protective effect of alpha-lipoic acid (ALA) on hearing loss in diabetic transgenic zebrafish and confirmed that ALA protects the loss of hair cells (HCs) caused by hyperglycemia. The data indicated that ALA has a protective effect on the damage to HCs in diabetic zebrafish.

Hypothyroidism: morphological and metabolic changes in the testis of adult albino rat and the amelioration by alpha-lipoic acid

The objective of this study is to evaluate the influence of carbimazole- induced hypothyroidism on the testes of adult albino rats and the probable protective effect of alpha-lipoic acid (ALA). The rats were divided into four groups; control group, ALA group, carbimazole, and carbimazole + ALA groups. Rats were exposed to ALA (60 mg/kg body weight) or carbimazole (1.35 mg/kg body weight), or both, administered via gavages for 30 days. Morphometric analysis revealed a significant decrease in tubular diameter, germinal epithelium thickness, and interstitial space as compared to the controls. Also, rats exposed to carbimazole showed a significant decline in testicular weight, sperm motility, and count. Additionally, deterioration of the testicular architecture was observed. ALA supplementation resulted in a significant improvement in the tubular diameter and germinal epithelium thickness, but no significant improvement regarding interstitial space was observed. Another observation was the significant decline in serum testosterone and follicle-stimulating hormone (FSH) in the carbimazole group, indicating reduced steroidogenesis. A significant reduction in reduced glutathione content was detected in the testes of the carbimazole group compared with the controls, while malonaldehyde concentration significantly increased. Conversely, ALA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, luteinizing hormone, and FSH levels, testicular steroidogenesis, and oxidative stress parameters. Hypothyroidism altered testicular antioxidant balance and negatively affected spermatogenesis. On the other hand, ALA through its antioxidant properties alleviated testicular toxicity in carbimazole-exposed rats.

Protective effect of alpha-lipoic acid on bisphenol A-induced learning and memory impairment in developing mice: nNOS and keap1/Nrf2 pathway

The adverse effects of bisphenol A (BPA) on learning and memory may be related with oxidative stress, but the mechanisms are unclear. This study aimed to investigate the mechanism of damaged learning and memory caused by BPA through inducing oxidative stress, as well as to explore whether alpha-lipoic acid (ALA) show a protective action. Female mice were exposed to 0.1 μg/mL BPA, 0.2 μg/mL BPA, 0.6 mg/mL ALA, and 0.2 BPA + ALA through drinking water for 8 weeks. The results showed that ALA protected against the impairment of spatial, recognition, and avoidance memory caused by BPA. ALA replenished the reduce of hippocampus coefficient, serum estradiol (E2) level, and hippocampal neurotransmitters levels induced by BPA. ALA alleviated BPA-induced oxidative stress and hippocampal histological changes. BPA exposure reduced the levels of synaptic structural proteins and PKC/ERK/CREB pathway proteins, and ALA improved these reductions. ALA altered the protein levels of nNOS and keap1/Nrf2 pathway affected by BPA. Our results suggested that impairments of learning and memory caused by BPA was related to the damage of hippocampal synapses mediated by oxidative stress, and ALA protected learning and memory by reducing the oxidative stress induced by BPA through regulating the nNOS and keap1/Nrf2 pathway.

Alpha lipoic acid improves heat stress-induced reduction of serum oestradiol and progesterone levels by affecting oxidative and endoplasmic reticulum stress in hens

Alpha lipoic acid (ALA), a natural lipophilic compound, plays an important role in regulating several metabolic pathways due to its antioxidant properties. This study aims to investigate whether ALA could be used as a feed additive to enhance the antioxidant capacity of the ovary tissue in hens exposed to heat stress (HS). One hundred and sixty 128-days-old female chickens were randomly assigned into four groups: the control group (Con), ALA treatment group (ALA), ALA and HS treatment group (ALA + HS), and HS treatment group (HS). The ALA and ALA + HS groups were fed a basal diet with 0.25% ALA, whereas the Con and HS groups were fed a basal diet only. Serum oestradiol, progesterone levels, biomarkers of antioxidant capacity, and endoplasmic reticulum (ER) stress markers were detected in the ovaries of heat-stressed chickens. HS decreased serum oestradiol and progesterone concentrations compared with the control group, whereas dietary ALA (0.25%) increased oestradiol and progesterone levels in the serum of heat-stressed hens. Malondialdehyde concentration in the ovary was higher in the HS group than that of the ALA + HS group. Compared with the HS group, ALA increased the enzymatic activities of superoxide dismutase, glutathione peroxidase, and catalase in the ovaries of ALA + HS group. Simultaneously, ALA enhanced the total antioxidative capacity of the ovaries of heat-stressed hens. Moreover, ALA also significantly inhibited the increased expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein homologous protein, which are two markers of ER stress, and heat shock protein 70, a key biomarker of heat stress, in the ovaries of the ALA + HS group as compared to those of the HS group. This work implied that dietary ALA supplementation improved the antioxidant capacity and attenuated the HS-induced reduction of serum oestradiol and progesterone levels and modulated the oxidative and ER stress, which are involved in the protective effect of ALA in hens exposed to hyperthermia.