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Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases. Causes of age-related macular degeneration Age-related macular degeneration (AMD) is a leading cause of blindness in older people. A polymorphism in complement factor H (CFH) has been strongly associated with the disease, but the mechanism of the association has been unclear. Here it is shown that CFH binds specifically to the lipid peroxidation product, malondialdehyde, which builds up in AMD as a result of oxidative stress. Malondialdehyde and malondialdehyde-modified proteins induce inflammatory responses; CFH neutralizes this inflammatory potential both in vitro and in the mouse retina. A common CFH polymorphism associated with AMD leads to impaired binding to malondialdehyde, potentially explaining why homozygous individuals with this polymorphism have a 6–7-fold increased risk of developing the condition.

Melatonin (MT; N-acetyI-5-methoxytryptamine) is an amine hormone involved in abiotic stress resistance. Previous studies have confirmed that melatonin can promote seed germination, mediate physiological regulation mechanisms, and stimulate crop growth under stress. However, the osmotic regulation mechanism by which exogenous melatonin mediates salt tolerance in cotton is still largely unknown. To investigate the effect of salt stress on melatonin concentration in germinating cotton seeds, we analyzed melatonin content over time during seed germination under different treatments. Melatonin content reached its minimum at day 6, while cotton germination rates peaked at day 6, indicating melatonin content and seed germination are correlated. Then we investigated the effects of 10-100 μM melatonin treatments on membrane lipid peroxides and osmotic adjustment substances during cotton seed germination under salt stress. Salt stress led to electrolyte leakage (EL) as well as accumulations of hydrogen peroxide (H2O2), malondialdehyde (MDA), organic osmotic substances (i.e., proline, soluble sugars), and inorganic osmotic substances (i.e., Na+, Cl-). Meanwhile, the contents of melatonin, soluble proteins, and K+ as well as the K+/Na+ balance decreased, indicating that salt stress inhibited melatonin synthesis and damaged cellular membranes, seriously affecting seed germination. However, melatonin pretreatment at different concentrations alleviated the adverse effects of salt stress on cotton seeds and reduced EL as well as the contents of H2O2, MDA, Na+, and Cl-. The exogenous application of melatonin also promoted melatonin, soluble sugar, soluble proteins, proline, and K+/Na+ contents under salt stress. These results demonstrate that supplemental melatonin can effectively ameliorate the repression of cotton seed germination by enhancing osmotic regulating substances and adjusting ion homeostasis under salt stress. Thus, melatonin may potentially be used to protect cotton seeds from salt stress, with the 20 μM melatonin treatment most effectively promoting cotton seed germination and improving salt stress tolerance.

Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play crucial roles in diverse fundamental biological processes. However, to date no study has reported miRNA-mediated regulation of ferroptosis. Here we show that miR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells. Ectopic expression of miR-137 suppressed SLC1A5, resulting in decreased glutamine uptake and malondialdehyde (MDA) accumulation. Meanwhile, antagomir-mediated inactivation of endogenous miR-137 increased the sensitivity of melanoma cells to erastin- and RSL3-induced ferroptosis. Importantly, knockdown of miR-137 increased the antitumor activity of erastin by enhancing ferroptosis both in vitro and in vivo. Collectively, these data indicate that miR-137 plays a novel and indispensable role in ferroptosis by inhibiting glutaminolysis and suggest a potential therapeutic approach for melanoma.

Acrylamide (ACR) is extensively used in industrial areas and has been demonstrated to induce neurotoxicity via oxidative stress and apoptosis. In this study, we assessed the probable protective effects of thymoquinone (TQ), an active constituent of Nigella sativa, against ACR-induced neurotoxicity. ACR (50 mg/kg, i.p., for 11 days) and TQ (2.5, 5 and 10 mg/kg, i.p., for 11 days) were administered to rats. On 12th day, gait score was examined and rats were sacrificed. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were determined in sciatic nerve. Furthermore, western blotting was conducted. The exposure of rats to ACR caused severe gait disabilities. The MDA and GSH contents were increased and decreased, respectively. ACR decreased P-ERK/ERK ratio and myelin basic protein (MBP) content, but significantly increased P-JNK/JNK, P-P38/P38, Bax/Bcl-2 ratios and caspase 3 and 9 levels. Concurrently administration of TQ (5 and 10 mg/kg) with ACR, prevented gait abnormalities and meaningfully reduced MDA and elevated the GSH contents. Furthermore, TQ (5 mg/kg) elevated the P-ERK/ERK ratio and MBP content while reduced the P-JNK/JNK, P-P38/P38 ratios and apoptotic markers. MAP kinase and apoptosis signaling pathways were involved in ACR-induced neurotoxicity in rat sciatic nerve and TQ significantly reduced ACR neurotoxicity. TQ afforded neuroprotection, in part, due to its anti-oxidative stress and anti-apoptotic mechanisms.

An excellent pre-column fluorescent derivatization reagent N-acetylhydrazine acridone for the quantitative determination of malondialdehyde was synthesized. Malondialdehyde was derivatized at 80 °C for 30 min in the presence of trichloroacetic acid. The separation of the derivative was performed on an Agilent ZORBAX SB-C18 column in conjunction with gradient elution. The excitation and emission wavelengths were 370 nm and 420 nm, respectively. The developed method demonstrated good linear relationship in the range of 0.02 pmol to 2.5 pmol (r = 0.9998). The calculated limit of detection and limit of quantification were 2.5 fmol and 8.3 fmol, respectively. The analytical precisions of the method were in the range of 1.36–2.27% (intra-day) and 2.36–3.92% (inter-day) respectively. The method was sensitive, specific and simple. It was successfully implemented to analysis the malondialdehyde in rat prostate.

Background Tungsten inert gas (TIG) welding represents one of the most widely used metal joining processes in industry. It has been shown to generate a large majority of particles at the nanoscale and to have low mass emission rates when compared to other types of welding. Despite evidence that TIG fume particles may produce reactive oxygen species (ROS), limited data is available for the time course changes of particle-associated oxidative stress in exposed TIG welders. Methods Twenty non-smoking male welding apprentices were exposed to TIG welding fumes for 60 min under controlled, well-ventilated settings. Exhaled breathe condensate (EBC), blood and urine were collected before exposure, immediately after exposure, 1 h and 3 h post exposure. Volunteers participated in a control day to account for oxidative stress fluctuations due to circadian rhythm. Biological liquids were assessed for total reducing capacity, hydrogen peroxide (H 2 O 2 ), malondialdehyde (MDA), and 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations at each time point. A linear mixed model was used to assess within day and between day differences. Results Significant increases in the measured biomarkers were found at 3 h post exposure. At 3 h post exposure, we found a 24 % increase in plasma-H 2 O 2 concentrations ([95%CI: 4 % to 46 %], p  = 0.01); a 91 % increase in urinary-H 2 O 2 ([2 % to 258 %], p  = 0.04); a 14 % increase in plasma-8-OHdG ([0 % to 31 %], p  = 0.049); and a 45 % increase in urinary-8-OHdG ([3 % to 105 %], p  = 0.03). Doubling particle number concentration (PNC) exposure was associated with a 22 % increase of plasma-8-OHdG at 3 h post exposure ( p  = 0.01). Conclusion A 60-min exposure to TIG welding fume in a controlled, well-ventilated setting induced acute oxidative stress at 3 h post exposure in healthy, non-smoking apprentice welders not chronically exposed to welding fumes. As mass concentration of TIG welding fume particles is very low when compared to other types of welding, it is recommended that additional exposure metrics such as PNC are considered for occupational risk assessments. Our findings highlight the importance of increasing awareness of TIG welding fume toxicity, especially given the realities of welding workplaces that may lack ventilation; and beliefs among interviewed welders that TIG represents a cleaner and safer welding process.

Ferroptosis is an iron-dependent regulated necrosis. This study aims to evaluate the contribution of ferroptosis to ischemia or reperfusion injury, and lay a basis for precise therapy of myocardial infarction. The Sprague-Dawley (SD) rat hearts were subjected to ischemia for different duration or the hearts were treated with 1 h-ischemia plus different duration of reperfusion. The myocardial injury was assessed by biochemical assays and hematoxylin & eosin (HE) staining. The ferroptosis was evaluated with the levels of acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), iron, and malondialdehyde. Iron chelator (deferoxamine) was applied to verify the contribution of ferroptosis to ischemia and reperfusion injury. The results showed that ischemic injury (infarction and CK release) was getting worse with the extension of ischemia, but no significant changes in ferroptosis indexes (ACSL4, GPX4, iron, and malondialdehyde) in cardiac tissues were observed. Differently, the levels of ACSL4, iron, and malondialdehyde were gradually elevated with the extension of reperfusion concomitant with a decrease of GPX4 level. In the ischemia-treated rat hearts, no significant changes in myocardial injury were observed in the presence of deferoxamine, while in the ischemia/reperfusion-treated rat hearts, myocardial injury was markedly attenuated in the presence of deferoxamine concomitant with a reduction of ferroptosis. Based on these observations, we conclude that ferroptosis occurs mainly in the phase of myocardial reperfusion but not ischemia. Thus, intervention of ferroptosis exerts beneficial effects on reperfusion injury but not ischemic injury, laying a basis for precise therapy for patients with myocardial infarction.

Anthropogenic activities are a major source for contaminating the agricultural soil with heavy metals, which can affect physiological and metabolic processes in plants. Among the heavy metals, chromium (Cr) is the most toxic pollutant that negatively affects plants’ metabolic activities, growth, and yield. Chromium reduces the plant growth and development by influencing the photosynthetic performance and antioxidant enzyme activities. This study was designed to examine the promotive role of exogenously applied glycinebetaine (GB) on plant morphophysiological and biochemical attributes in cauliflower ( Brassica oleracea botrytis L.) under Cr toxicity. Four levels (0, 10, 100, and 200 μM) of Cr were tested under the application of GB (1 mM). The results delineated that Cr stress caused a considerable reduction in plant growth, photosynthetic pigment, gas exchange parameters, and biomass production. At high concentration (200 μM), chromium stress decreased the plant height (57%), root length (32%), number of leaves (45%), and leaf area (29%) as compared with controls. Due to Cr stress, the electrolyte leakage and accumulation of malondialdehyde and hydrogen peroxide increased both in the roots and leaves of cauliflower, whereas antioxidative enzyme activities (SOD, CAT, and POD) decreased both in the roots and leaves of cauliflower due to Cr stress. At 200 μM of chromium treatment, root dry weight, stem dry weight, leaf dry weight, and flower dry weight declined up to 43%, 40%, 53%, and 72%, respectively. With the application of GB, dry biomass of plant increased significantly as compared with no GB treatment under chromium stress. As Cr level increased in growth media, its concentration also increased in all plant parts including roots, stem, leaves, and flowers. However, GB application efficiently alleviated the Cr toxic effects on cauliflower and maintained higher plant growth, biomass production, photosynthetic attributes, and gas exchange traits as compared with their respective controls. Exogenously applied GB decreased oxidative stress and improved antioxidative enzyme activities as compared with treatments without GB application. Furthermore, Cr concentrations taken by plants were decreased due to GB application. These findings suggest that GB can play a positive role to maintain plant morphology and photosynthetic attributes under Cr toxic conditions in cauliflower.

This mini review is devoted to a specific issue: the role of malondialdehyde (MDA)—a secondary product of free radical lipid peroxidation—in the molecular mechanisms of the formation of primary atherosclerotic vascular wall lesions. The principal difference between this review and the available literature is that it discusses in detail the important role in atherogenesis not of “oxidized” LDL (i.e., LDL particles containing lipohydroperoxides), but of LDL particles chemically modified by the natural low-molecular weight dicarbonyl MDA. To confirm this, we consider the data obtained by us earlier, indicating that “atherogenic” are not LDL oxidized as a result of free radical lipoperoxidation and containing lipohydroperoxy derivatives of phospholipids in the outer layer of particles, but LDL whose apoprotein B-100 has been modified due to the chemical reaction of terminal lysine residue amino groups of the apoB-100 with the aldehyde groups of the MDA (Maillard reaction). In addition, we present our original data proving that MDA injures endothelial glycocalyx that suppress the ability of the endothelium to control arterial tone according to changes in wall shear stress. In summary, this mini review for the first time exhaustively discloses the key role of MDA in atherogenesis.