Melatonin and Indole-3-Propionic Acid Reduce Oxidative Damage to Membrane Lipids Induced by High Iron Concentrations in Porcine Skin

Iron excess in tissues results in increased oxidative damage. Among different tissues, the skin can particularly be severely damaged by oxidative stress, as it is exposed not only to endogenous but also directly to exogenous pro-oxidants. The skin is especially vulnerable to harmful oxidative stress. Melatonin and indole-3-propionic acid (IPA), two indole substances, are efficient antioxidants. This study aims to evaluate the potential protective effects of melatonin and IPA against oxidative damage to membrane lipids (lipid peroxidation (LPO)), induced in porcine skin homogenates by the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO4 (2400, 1200, 600, 300, 150 and 75 µM) + H2O2 (5 mM) with/without melatonin or IPA. LPO level (MDA + 4-HDA/mg protein) was measured spectrophotometrically. Melatonin, in its highest used concentration (5.0 mM), prevented FeSO4 (1200 mM)-induced LPO, whereas it was effective in concentrations as low as 2.5 mM against all lower iron concentrations. IPA was protective in concentrations as low as 2.5 mM independently of FeSO4 concentration. In conclusion, melatonin and IPA effectively protect against oxidative damage to membrane lipids induced by high concentrations of iron in porcine skin; therefore, both can be considered pharmacological agents in the case of disorders associated with excessive iron accumulation in the skin.

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Cumulative Protective Effect of Melatonin and Indole-3-Propionic Acid against KIO3—Induced Lipid Peroxidation in Porcine Thyroid

Toxics ◽

10.3390/toxics9050089 ◽

2021 ◽

Vol 9 (5) ◽

pp. 89

Author(s):

Paulina Iwan ◽

Jan Stepniak ◽

Malgorzata Karbownik-Lewinska

Keyword(s):

Lipid Peroxidation ◽

Thyroid Cancer ◽

Oxidative Damage ◽

Propionic Acid ◽

Membrane Lipids ◽

Iodine Concentration ◽

Protective Effects ◽

Experimental Conditions ◽

Salt Iodization

Iodine deficiency is the main environmental factor leading to thyroid cancer. At the same time iodine excess may also contribute to thyroid cancer. Potassium iodate (KIO3), which is broadly used in salt iodization program, may increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO3 concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin and indole-3-propionic acid (IPA) are effective antioxidative indoles, each of which protects against KIO3-induced LPO in the thyroid. The study aims to check if melatonin used together with IPA (in their highest achievable in vitro concentrations) reveals stronger protective effects against KIO3-induced LPO in porcine thyroid homogenates than each of these antioxidants used separately. Homogenates were incubated in the presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25; 0.0 mM) without/with melatonin (5 mM) or without/with IPA (10 mM) or without/with melatonin + IPA, and then, to further clarify the narrow range of KIO3 concentrations, against which melatonin + IPA reveal cumulative protective effects, the following KIO3 concentrations were used: 20; 18.75; 17.5; 16.25; 15; 13.75; 12.5; 11.25; 10; 8.75; 7.5; 0.0 mM. Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Protective effects of melatonin + IPA were stronger than those revealed by each antioxidant used separately, but only when LPO was induced by KIO3 in concentrations from 18.75 mM to 8.75 mM, corresponding to physiological iodine concentration in the thyroid. In conclusion, melatonin and indole-3-propionic acid exert cumulative protective effects against oxidative damage caused by KIO3, when this prooxidant is used in concentrations close to physiological iodine concentrations in the thyroid. Therefore, the simultaneous administration of these two indoles should be considered to prevent more effectively oxidative damage (and thereby thyroid cancer formation) caused by iodine compounds applied in iodine prophylaxis.

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Fenton Reaction-Induced Oxidative Damage to Membrane Lipids and Protective Effects of 17β-Estradiol in Porcine Ovary and Thyroid Homogenates

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17186841 ◽

2020 ◽

Vol 17 (18) ◽

pp. 6841

Author(s):

Aleksandra Rynkowska ◽

Jan Stępniak ◽

Małgorzata Karbownik-Lewińska

Keyword(s):

Hydrogen Peroxide ◽

Lipid Peroxidation ◽

Oxidative Damage ◽

Fenton Reaction ◽

Membrane Lipids ◽

Iron Concentration ◽

Protective Effects ◽

17Β Estradiol ◽

Higher Sensitivity ◽

Experimentally Induced

The Fenton reaction (Fe2++H2O2→Fe3++•OH+OH-) results in strong oxidative damage to macromolecules when iron (Fe) or hydrogen peroxide (H2O2) are in excess. This study aims at comparing Fe2++H2O2-induced oxidative damage to membrane lipids (lipid peroxidation, LPO) and protective effects of 17β-estradiol (a potential antioxidant) in porcine ovary and thyroid homogenates. Iron, as one of the Fenton reaction substrates, was used in the highest achievable concentrations. Thyroid or ovary homogenates were incubated in the presence of: (1st) FeSO4+H2O2 with/without 17β-estradiol (1 mM; 100, 10.0, 1.0 µM; 100, 10.0, 1.0 nM; 100, 10.0, 1.0 pM); five experiments were performed with different FeSO4 concentrations (2400, 1200, 600, 300, 150 µM); (2nd) FeSO4 (2400, 1200, 600, 300, 150 µM)+H2O2 with/without 17β-estradiol; three experiments were performed with three highest 17β-estradiol concentrations; (3rd) FeSO4 (2400, 1200, 1100, 1000, 900, 800, 700, 600, 300, 150, 75 µM)+H2O2 (5 mM). LPO level [MDA+4-HDA/mg protein] was measured spectrophotometrically. The basal LPO level is lower in ovary than in thyroid homogenates. However, experimentally-induced LPO was higher in the former tissue, which was confirmed for the three highest Fe2+ concentrations (2400, 1200, 1100 µM). Exogenous 17β-estradiol (1 mM, 100, and 10 µM) reduced experimentally-induced LPO independently of iron concentration and that protective effect did not differ between tissues. The ovary, compared to the thyroid, reveals higher sensitivity to prooxidative effects of iron, however, it showed similar responsivity to protective 17β-estradiol activity. The therapeutic effect of 17β-estradiol against iron overload consequences should be considered with relation to both tissues.

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Melatonin reduces high levels of lipid peroxidation induced by potassium iodate in porcine thyroid

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000628 ◽

2019 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Paulina Iwan ◽

Jan Stepniak ◽

Malgorzata Karbownik-Lewinska

Keyword(s):

Lipid Peroxidation ◽

Oxidative Damage ◽

Membrane Lipids ◽

Chemical Properties ◽

Iodine Concentration ◽

Free Radical Scavenger ◽

Radical Scavenger ◽

Protective Effects ◽

Potassium Iodate ◽

Hormone Synthesis

Abstract. Iodine is essential for thyroid hormone synthesis. Under normal iodine supply, calculated physiological iodine concentration in the thyroid is approx. 9 mM. Either potassium iodide (KI) or potassium iodate (KIO3) are used in iodine prophylaxis. KI is confirmed as absolutely safe. KIO3 possesses chemical properties suggesting its potential toxicity. Melatonin (N-acetyl-5-methoxytryptamine) is an effective antioxidant and free radical scavenger. Study aims: to evaluate potential protective effects of melatonin against oxidative damage to membrane lipids (lipid peroxidation, LPO) induced by KI or KIO3 in porcine thyroid. Homogenates of twenty four (24) thyroids were incubated in presence of either KI or KIO3 without/with melatonin (5 mM). As melatonin was not effective against KI-induced LPO, in the next step only KIO3 was used. Homogenates were incubated in presence of KIO3 (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25 mM) without/with melatonin or 17ß-estradiol. Five experiments were performed with different concentrations of melatonin (5.0; 2.5; 1.25; 1.0; 0.625 mM) and one with 17ß-estradiol (1.0 mM). Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. KIO3 increased LPO with the strongest damaging effect (MDA + 4-HDA level: ≈1.28 nmol/mg protein, p < 0.05) revealed at concentrations of around 15 mM, thus corresponding to physiological iodine concentrations in the thyroid. Melatonin reduced LPO (MDA + 4-HDA levels: from ≈0.97 to ≈0,76 and from ≈0,64 to ≈0,49 nmol/mg protein, p < 0.05) induced by KIO3 at concentrations of 10 mM or 7.5 mM. Conclusion: Melatonin can reduce very strong oxidative damage to membrane lipids caused by KIO3 used in doses resulting in physiological iodine concentrations in the thyroid.

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Ethanol Extract of Maclura tricuspidata Fruit Protects SH-SY5Y Neuroblastoma Cells against H2O2-Induced Oxidative Damage via Inhibiting MAPK and NF-κB Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms22136946 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6946

Author(s):

Weishun Tian ◽

Suyoung Heo ◽

Dae-Woon Kim ◽

In-Shik Kim ◽

Dongchoon Ahn ◽

...

Keyword(s):

Oxidative Stress ◽

Free Radical ◽

Oxidative Damage ◽

Cell Damage ◽

Antioxidant Properties ◽

Radical Scavenging ◽

Biologically Active ◽

Mitogen Activated Protein Kinase ◽

Protective Effects ◽

Neuroprotective Effects

Free radical generation and oxidative stress push forward an immense influence on the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Maclura tricuspidata fruit (MT) contains many biologically active substances, including compounds with antioxidant properties. The current study aimed to investigate the neuroprotective effects of MT fruit on hydrogen peroxide (H2O2)-induced neurotoxicity in SH-SY5Y cells. SH-SY5Y cells were pretreated with MT, and cell damage was induced by H2O2. First, the chemical composition and free radical scavenging properties of MT were analyzed. MT attenuated oxidative stress-induced damage in cells based on the assessment of cell viability. The H2O2-induced toxicity caused by ROS production and lactate dehydrogenase (LDH) release was ameliorated by MT pretreatment. MT also promoted an increase in the expression of genes encoding the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). MT pretreatment was associated with an increase in the expression of neuronal genes downregulated by H2O2. Mechanistically, MT dramatically suppressed H2O2-induced Bcl-2 downregulation, Bax upregulation, apoptotic factor caspase-3 activation, Mitogen-activated protein kinase (MAPK) (JNK, ERK, and p38), and Nuclear factor-κB (NF-κB) activation, thereby preventing H2O2-induced neurotoxicity. These results indicate that MT has protective effects against H2O2-induced oxidative damage in SH-SY5Y cells and can be used to prevent and protect against neurodegeneration.

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Four Novel Dammarane-Type Triterpenoids from Pearl Knots of Panax ginseng Meyer cv. Silvatica

Molecules ◽

10.3390/molecules24061159 ◽

2019 ◽

Vol 24 (6) ◽

pp. 1159 ◽

Cited By ~ 1

Author(s):

Zeng Qi ◽

Zhuo Li ◽

Xuewa Guan ◽

Cuizhu Wang ◽

Fang Wang ◽

...

Keyword(s):

Oxidative Stress ◽

Inflammatory Response ◽

Oxidative Damage ◽

Cigarette Smoke ◽

Panax Ginseng ◽

Inflammatory Reaction ◽

A549 Cells ◽

Protective Effects

Panax ginseng Meyer cv. Silvatica (PGS), which is also known as “Lin-Xia-Shan-Shen” or “Zi-Hai” in China, is grown in forests and mountains by broadcasting the seeds of ginseng and is harvested at the cultivation age of 15–20 years. In this study, four new dammarane-type triterpenoids, ginsengenin-S1 (1), ginsengenin-S2 (2), ginsenoside-S3 (3), ginsenoside-S4 (4), along with one known compound were isolated from pearl knots of PGS. Ginsengenin-S2 significantly alleviated oxidative damage when A549 cells were exposed to cigarette smoke (CS) extract. In addition, ginsengenin-S2 could inhibit the CS-induced inflammatory reaction in A549 cells. Protective effects of ginsengenin-S2 against CS-mediated oxidative stress and the inflammatory response in A549 cells may involve the Nrf2 and HDAC2 pathways.

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Protective effects of a cocktail of lactic acid bacteria on microcystin-LR-induced hepatotoxicity and oxidative damage in BALB/c mice

RSC Advances ◽

10.1039/c7ra03035e ◽

2017 ◽

Vol 7 (33) ◽

pp. 20480-20487 ◽

Cited By ~ 1

Author(s):

Jichun Zhao ◽

Fengwei Tian ◽

Qixiao Zhai ◽

Ruipeng Yu ◽

Hao Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Lactic Acid ◽

Lactic Acid Bacteria ◽

Oxidative Damage ◽

Protective Effects ◽

And Oxidative Stress

The aim of this study was to investigate the effects of mixed lactic acid bacteria (LAB) against microcystin-LR-exposed hepatotoxicity and oxidative stress in BALB/c mice.

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Melatonin reduces oxidative damage in mouse granulosa cells via restraining JNK-dependent autophagy

Reproduction ◽

10.1530/rep-18-0002 ◽

2018 ◽

Vol 155 (3) ◽

pp. 307-319 ◽

Cited By ~ 7

Author(s):

Yan Cao ◽

Ming Shen ◽

Yi Jiang ◽

Shao-chen Sun ◽

Honglin Liu

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

Mammalian Cells ◽

Therapeutic Strategies ◽

Oxygen Species ◽

Protective Effects ◽

Follicular Atresia ◽

Direct Role ◽

Jnk Pathway

Oxidative stress-induced granulosa cell (GCs) injury is believed to be a common trigger for follicular atresia. Emerging evidence indicates that excessive autophagy occurs in mammalian cells with oxidative damage. N-acetyl-5-methoxytrypamine (melatonin) has been shown to prevent GCs from oxidative injury, although the exact mechanism remains to be elucidated. Here, we first demonstrated that the suppression of autophagy through the JNK/BCL-2/BECN1 signaling is engaged in melatonin-mediated GCs protection against oxidative damage. Melatonin inhibited the loss of GCs viability, formation of GFP-MAP1LC3B puncta, accumulation of MAP1LC3B-II blots, degradation of SQSTM1 and the expression of BECN1, which was correlated with impaired activation of JNK during oxidative stress. On the other hand, blocking of autophagy and/or JNK also reduced the level of H2O2-induced GCs death, but failed to further restore GCs viability in the presence of melatonin. Particularly, the suppression of autophagy provided no additional protective effects when GCs were pretreated with JNK inhibitor and/or melatonin. Importantly, we found that the enhanced interaction between BCL-2 and BECN1 might be a responsive mechanism for autophagy suppression via the melatonin/JNK pathway. Moreover, blocking the downstream antioxidant system of melatonin using specific inhibitors further confirmed a direct role of melatonin/JNK/autophagy axis in preserving GCs survival without scavenging reactive oxygen species (ROS). Taken together, our findings uncover a novel function of melatonin in preventing GCs from oxidative damage by targeting JNK-mediated autophagy, which might contribute to develop therapeutic strategies for patients with ovulation failure-related disorders.

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Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration

F1000Research ◽

10.12688/f1000research.19598.1 ◽

2019 ◽

Vol 8 ◽

pp. 1067 ◽

Cited By ~ 1

Author(s):

Faith A. Kwa ◽

Nabeela K. Dulull ◽

Ute Roessner ◽

Daniel A. Dias ◽

Thusitha W. Rupasinghe

Keyword(s):

Oxidative Stress ◽

Mass Spectrometry ◽

Hydrogen Peroxide ◽

Fatty Acids ◽

Cell Proliferation ◽

Fatty Acid ◽

Oxidative Damage ◽

Disease Progression ◽

Protective Effects ◽

Retinal Cells

Background: Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients’ quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection. Methods: The in vitro oxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry. Results: Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolamine lipids. Conclusions: We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD.

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Partially Hydrolyzed Guar Gum Attenuates d-Galactose-Induced Oxidative Stress and Restores Gut Microbiota in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms20194861 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4861 ◽

Cited By ~ 1

Author(s):

Xiaoyan Liu ◽

Chenxuan Wu ◽

Dong Han ◽

Jun Liu ◽

Haijie Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Oxidative Damage ◽

Guar Gum ◽

Telomerase Activity ◽

Sirtuin 1 ◽

Protective Effects ◽

Rat Serum ◽

Oxidative Damages ◽

Partially Hydrolyzed Guar Gum

Partially hydrolyzed guar gum (PHGG) has received considerable attention for its various bioactive functions. The injection of d-galactose can cause aging-related injury which is usually resulted from oxidative stress on tissues and cells. In this study, d-galactose (200 mg/kg/day) was injected into rats, and the protective effects of PHGG (500, 1000, and 1500 mg/kg/day) against oxidative damages, as well as its probiotic functions, were analyzed. The results showed that PHGG treatment at a concentration of 1500 mg/kg/day greatly reduced the levels of lactic acid, nitric oxide, inducible nitric oxide synthase, advanced glycation end products, and increased the telomerase activity, by 7.60%, 9.25%, 12.28%, 14.58%, and 9.01%, respectively. Moreover, PHGG significantly elevated the activities of antioxidant enzymes and decreased the content of malondialdehyde in rat serum and brain. The oxidative damage was also significantly alleviated in the liver and hippocampus and the expressions of brain-derived neurotrophic factor and choline acetyltransferase also increased. Furthermore, PHGG treatment could significantly regulated the expression of sirtuin 1, forkhead box O1, and tumor protein p53 in the hippocampus. It also increased the levels of organic acids and improved the composition of intestinal microbiota. These findings demonstrated that PHGG treatment could effectively alleviate the oxidative damage and dysbacteriosis.

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After In Vitro Digestion, Jackfruit Flake Affords Protection against Acrylamide-Induced Oxidative Damage

Molecules ◽

10.3390/molecules24183322 ◽

2019 ◽

Vol 24 (18) ◽

pp. 3322 ◽

Cited By ~ 1

Author(s):

Daofeng Qu ◽

Chu Liu ◽

Mengxue Jiang ◽

Lifang Feng ◽

Yuewen Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Oxidative Damage ◽

High Performance ◽

In Vitro Digestion ◽

Protective Effects ◽

Physical Damage ◽

Before And After ◽

High Content Analysis ◽

High Level

Some studies have demonstrated that acrylamide (AA) was correlated with oxidative stress, resulting in physical damage. The jackfruit flake was an immature pulp that contained a high level of antioxidant activity. This study aimed to assess the defensive efficacy of jackfruit flake in AA-induced oxidative stress before and after simulated gastrointestinal digestion. Our results indicate that the total polyphenol content of Jackfruit flake digest (Digestive products of jackfruit flake after gastrointestinal, JFG) was diminished; however, JFG had raised the relative antioxidant capacity compared to Jackfruit flake extract (JFE). Additionally, the results of High Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) implied that a proportion of compounds were degraded/converted into other unknown and/or undetected metabolites. Further, by high content analysis (HCA) techniques, JFG markedly reduced cytotoxicity and excessive production of reactive oxygen species (ROS) in cells, thereby alleviating mitochondrial disorders. In this study, it may be converted active compounds after digestion that had preferable protective effects against AA-induced oxidative damage.

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