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Journal of Alzheimer's Disease : JAD Sep 2007In this study, we evaluated the effect of lipoic acid (LA) and N-acetyl cysteine (NAC) on oxidative [4-hydroxy-2-nonenal, N(epsilon)-(carboxymethyl)lysine and heme... (Review)
Review
In this study, we evaluated the effect of lipoic acid (LA) and N-acetyl cysteine (NAC) on oxidative [4-hydroxy-2-nonenal, N(epsilon)-(carboxymethyl)lysine and heme oxygenase-1] and apoptotic (caspase 9 and Bax) markers in fibroblasts from patients with Alzheimer disease (AD) and age-matched and young controls. AD fibroblasts showed the highest levels of oxidative stress, and the antioxidants, lipoic acid (1 mM) and/or N-acetyl cysteine (100 microM) exerted a protective effect as evidenced by decreases in oxidative stress and apoptotic markers. Furthermore, we observed that the protective effect of LA and NAC was more pronounced when both agents were present simultaneously. AD-type changes could be generated in control fibroblasts using N-methylprotoporphyrin to inhibit cytochrome oxidase assembly indicating that the the oxidative damage observed was associated with mitochondrial dysfunction. The effects of N-methylprotoporphyrine were reversed or attenuated by both lipoic acid and N-acetyl cysteine. These data suggest mitochondria are important in oxidative damage that occurs in AD. As such, antioxidant therapies based on lipoic acid and N-acetyl cysteine supplementation may be promising.
Topics: Acetylcysteine; Alzheimer Disease; Fibroblasts; Humans; Immunohistochemistry; Mitochondria; Oxidative Stress; Thioctic Acid
PubMed: 17917164
DOI: 10.3233/jad-2007-12210 -
Journal of Agricultural and Food... Sep 2020During this research a simple, accurate, and environmentally friendly method to determine lipoyllysine and lipoic acid in meat was developed and validated. The presented...
During this research a simple, accurate, and environmentally friendly method to determine lipoyllysine and lipoic acid in meat was developed and validated. The presented approach was based on the hydrolysis of the proteins containing lipoic acid, reduction of disulfide bonds with tris(hydroxymethyl)phosphine, and precolumn derivatization of free thiol groups with 1-benzyl-2-chloropyridinium bromide long-term followed by HPLC separation with a diode-array detector. The method has been validated in accordance with the U.S. FDA guidelines and was linear in the range of 0.1-10 μmol/L in concentration with values ≥0.9997 for both analytes. For lipoyllysine and lipoic acid, intra- and interday precision values were lower than 10%. The intraday accuracy values ranged from 91.0% to 99.4% for lipoyllysine and from 99.1% to 107.3% for lipoic acid, whereas the interday accuracy values for lipoyllysine and lipoic acid were 92.0-95.6% and 93.5-98.8%, respectively. Additionally, in this research the antioxidant activity of lipoyllysine and reduced lipoyllysine compound using spectrophotometric method with 1,1-diphenyl-2-picrylhydrazyl was examined for the first time. The data showed that dihydrolipoyllysine exhibits stronger antioxidant capacity than lipoyllysine based on a lower value of concentration required to achieve a 50% antioxidant effect in 1,1-diphenyl-2-picrylhydrazyl radical scavenging test.
Topics: Animals; Antioxidants; Cattle; Chickens; Chromatography, High Pressure Liquid; Hydrolysis; Lysine; Meat; Mice; Rats; Thioctic Acid
PubMed: 32886880
DOI: 10.1021/acs.jafc.0c03778 -
European Review For Medical and... Jul 2018Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of... (Review)
Review
OBJECTIVE
Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new safe and effective compounds are highly warranted, namely if based on an adequate understanding of the pathogenic mechanisms.
MATERIAL AND METHODS
Herein we reviewed and discussed scientific data related to the beneficial role of some non-conventional treatments able to counteract CIPN, focusing our attention on alpha-lipoic acid (ALA) and L-acetyl-carnitine (LAC), two natural products that have been demonstrated to be promising preventive drugs.
RESULTS
Although a growing body of in vitro and in vivo studies support ALA as a molecule able to counteract CIPN symptoms, mostly due to its antioxidant and anti-inflammatory properties, only two randomized clinical trials evaluated ALA usefulness in preventing chemotherapy-related neuropathy. Unfortunately, these studies were inconclusive and clinical outcomes showed to be highly dependent on the route of administration (oral versus or intravenous injection). LAC has demonstrated beneficial effects on both in vitro and in animal studies. Yet, some controversies aroused from randomized clinical trials. Indeed, while CIPN-patients treated with Taxane showed no benefit from LAC treatment, CIPN-patients treated with platinum compounds exhibit significant improvement of CIPN-related symptoms. Therefore, LAC treatment should be used, and thoroughly investigated only in patients treated with chemotherapy protocols Taxanes-free.
CONCLUSIONS
Mechanisms of toxicity triggered by each single drug need to be deeply explored to better identify effective compounds to prevent or treat them. Moreover, additional experiments are mandatory to establish effective doses and length of treatment for each clinical situation in order to perform large and long-term randomized studies.
Topics: Acetylcarnitine; Animals; Antineoplastic Agents; Biological Products; Humans; Peripheral Nervous System Diseases; Randomized Controlled Trials as Topic; Thioctic Acid
PubMed: 30058711
DOI: 10.26355/eurrev_201807_15534 -
BioMed Research International 2019Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that... (Review)
Review
Αlpha-lipoic acid is a naturally occurring antioxidant in human body and has been widely used as an antioxidant clinically. Accumulating evidences suggested that -lipoic acid might have immunomodulatory effects on both adaptive and innate immune systems. This review focuses on the evidences and potential targets involved in the immunomodulatory effects of -lipoic acid. It highlights the fact that -lipoic acid may have beneficial effects in autoimmune diseases once the immunomodulatory effects can be confirmed by further investigation.
Topics: Animals; Antioxidants; Autoimmune Diseases; Humans; Immunologic Factors; Thioctic Acid
PubMed: 31016198
DOI: 10.1155/2019/8086257 -
International Journal of Environmental... Feb 2021α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the...
α-Lipoic acid (ALA) and its reduced form dihydrolipoic acid (DHLA) are endogenous dithiol compounds with significant antioxidant properties, both of which have the potential to detoxify cells. In this study, ALA (250 μM) and DHLA (50 μM) were applied to reduce metal (As, Cd, and Pb)-induced toxicity in PC12 and Caco-2 cells as simultaneous exposure. Both significantly decreased Cd (5 μM)-, As (5 μM)-, and Pb (5 μM)-induced cell death. Subsequently, both ALA and DHLA restored cell membrane integrity and intracellular glutathione (GSH) levels, which were affected by metal-induced toxicity. In addition, DHLA protected PC12 cells from metal-induced DNA damage upon co-exposure to metals. Furthermore, ALA and DHLA upregulated the expression of survival-related proteins mTOR (mammalian target of rapamycin), Akt (protein kinase B), and Nrf2 (nuclear factor erythroid 2-related factor 2) in PC12 cells, which were previously downregulated by metal exposure. In contrast, in Caco-2 cells, upon co-exposure to metals and ALA, Nrf2 was upregulated and cleaved PARP-1 (poly (ADP-ribose) polymerase-1) was downregulated. These findings suggest that ALA and DHLA can counterbalance the toxic effects of metals. The protection of ALA or DHLA against metal toxicity may be largely due to an enhancement of antioxidant defense along with reduced glutathione level, which ultimately reduces the cellular oxidative stress.
Topics: Animals; Antioxidants; Caco-2 Cells; Humans; Oxidative Stress; PC12 Cells; Rats; Thioctic Acid
PubMed: 33671655
DOI: 10.3390/ijerph18042126 -
Actas Dermo-sifiliograficas 2017
Review
Topics: Burning Mouth Syndrome; Capsaicin; Cognitive Behavioral Therapy; Disease Management; Humans; Saliva, Artificial; Selective Serotonin Reuptake Inhibitors; Thioctic Acid
PubMed: 27702434
DOI: 10.1016/j.ad.2016.08.005 -
Annals of Nutrition & Metabolism 2016It has been generally accepted that being overweight or obese is a risk factor for several types of cancers, including breast, thyroid, colon, pancreatic and liver. In... (Review)
Review
BACKGROUND
It has been generally accepted that being overweight or obese is a risk factor for several types of cancers, including breast, thyroid, colon, pancreatic and liver. In fact, people who are obese have more fat tissues that can produce hormones, such as insulin or estrogen, which may cause cancer cells to grow. Alpha lipoic acid (ALA) is anorganosulfur compound derived from octanoic acid, which is produced in animals normally, and is essential for aerobic metabolism.
SUMMARY
Studies in both in vitro cells and in vivo animal models have shown that ALA inhibits the initiation and promotion stages of carcinogenesis, suggesting that ALA has considerable attention as a chemopreventive agent. This brief review collects the scattered data available in the literature concerning ALA and highlights its anti-cancer properties, intermediary metabolism and exploratory implications.
KEY MESSAGES
Based on scientific evidences so far, ALA might be useful agents in the management or chemoprevention of obesity-related cancers.
Topics: Animals; Antioxidants; Humans; Neoplasms; Obesity; Thioctic Acid
PubMed: 26829711
DOI: 10.1159/000443994 -
Microbiology and Molecular Biology... Jun 2010Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly... (Review)
Review
Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.
Topics: Animals; Apicomplexa; Bacteria; Fungi; Models, Biological; Thioctic Acid
PubMed: 20508247
DOI: 10.1128/MMBR.00008-10 -
The Journal of Biological Chemistry Dec 1963
Topics: Amidohydrolases; Chromatography; Enterococcus faecalis; Escherichia coli; Lysine; Pyruvates; Research; Thioctic Acid
PubMed: 14086741
DOI: No ID Found -
European Review For Medical and... Oct 2022Glucocorticoid-induced osteonecrosis is a serious debilitating health problem. In the present study, we investigated the effects of alpha-lipoic acid on...
OBJECTIVE
Glucocorticoid-induced osteonecrosis is a serious debilitating health problem. In the present study, we investigated the effects of alpha-lipoic acid on glucocorticoid-induced osteonecrosis in rats.
MATERIALS AND METHODS
A total of 40 male Wistar albino rats were equally assigned to 4 groups as control, methylprednisolone acetate (MPA), alpha-lipoic acid (ALA), and methylprednisolone acetate with alpha-lipoic acid (MPA+ALA). The animals in MPA group subcutaneously received 15 mg/kg/week for 2 weeks, whereas 100 mg/kg/day alpha-lipoic acid was intraperitoneal administered for 4 weeks to ALA group. The MPA+ALA group was subjected to both treatments in same doses. Osteonecrosis was confirmed and graded histologically. The serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, prothrombin time and activated partial thromboplastin time were evaluated. Also, lipid peroxidation and DNA damage were immunohistochemically assessed in the bone.
RESULTS
Osteonecrotic lesions were narrower in the MPA+ALA group than in the MPA group (p<0.05). As compared to the controls, the biochemical parameters in MPA and MPA+ALA groups were significantly increased (p<0.001). The oxidative stress index was significantly higher in the groups with MPA than the controls (p=0.002), but the animals treated with ALA alongside MPA displayed lesser scores than the ones injected with solely MPA (p=0.03). The administration of MPA elevated lipid peroxidation and DNA damage, which were successfully alleviated by ALA.
CONCLUSIONS
Alpha-lipoic acid may be suggested to be a protective supplement in glucocorticoid-induced osteonecrosis in rats. The antioxidant capacity of alpha-lipoic acid may involve its beneficial effects.
Topics: Animals; Rats; Male; Thioctic Acid; Antioxidants; Methylprednisolone Acetate; Glucocorticoids; Rats, Wistar; Oxidative Stress; Osteonecrosis
PubMed: 36314310
DOI: 10.26355/eurrev_202210_30009