Free Radical Research

Curcumin, an extensively studied phytochemical compound, has gained attention for its potential therapeutic applications across a spectrum of diseases. Its notable attributes include its relatively high tolerability within the human body and its perceived absence of adverse side effects. This review article presents a comprehensive overview of the antioxidant effects exhibited by complexes formed by curcumin and curcumin derived ligands with metals like Mn, Cu, Fe, Zn, Ga and In, which leads to toxic effects beyond a certain limit, based on both experimental and theoretical findings...

In the model system of DOPC (1,2- d iole o yl-sn-glycero-3- p hospho c holine) liposomes exposed to peroxyl radicals generated by the azoinitiator AAPH, cemtirestat (CMTI-SH) inhibited lipid peroxidation more efficiently than the natural antioxidant glutathione. In the concentrations 100 to 500 µM, both CMTI-SH and GSH induced distinct lag phases in the initial stages of lipid peroxidation yet GSH produced consistently shorter induction periods (about twice) than equimolar CMTI-SH. Moreover, concentration dependence of lipid peroxidation inhibition measured at the 80th minute, revealed about three times higher IC50 value for GSH compared to CMTI-SH...

Immense gains in understanding of mechanisms and effects of lipid oxidation have been achieved in the nearly 90 years over which lipid oxidation has been an active research focus. Even so, the substantial questions still being raised about lipid oxidation in this special issue show clearly that missing pieces remain and must be considered for full accounting of this important reaction in any system. In this context, epoxides are spotlighted as a critical overlooked product of lipid autoxidation - underestimated in analysis, underestimated in presence as a functionally active and competitive intermediate and product of lipid oxidation, and underestimated in potential contributions to impact of lipid oxidation on other molecules and cell functions...

Chronic obstructive pulmonary disease (COPD) is defined by inflammation and emphysema. Sirtuins (SIRT) are NAD+ -dependent histone deacetylases that regulate oxidative stress and inflammation. The present work investigates the modulatory role of SIRT-2 in experimental COPD model. Insilico comparative assessment of SIRT-2 inhibitors (AK-7 and AGK-2) by ADMET and molecular docking revealed AK-7 as suitable candidate for invivo application. COPD in mice was established by cigarette smoke (CS) exposure for 2 months...

Coordination of metal ions by the tetrapyrrole ring of porphyrin-based photosensitizers (PSs) affects their photophysical properties and consequently, their photodynamic activity. Diamagnetic metals increase the singlet oxygen quantum yield while paramagnetic metals have the opposite effect. Since singlet oxygen is considered the main cell-damaging species in photodynamic therapy (PDT), the nature of the chelated cation would directly affect PDT efficacy. This expectation, however, is not always supported by experimental results and numerous exceptions have been reported...

This study aimed to evaluate the protective role of N-acetylcysteine (NAC) in cells and mice exposed to formaldehyde. For the in vitro study, J774A.1 macrophages cells were incubated for 8, 16 and 24 h with formaldehyde or NAC to assess cell viability and reactive oxygen species (ROS). In the in vivo study, C57BL/6 mice ( n  = 48) were divided into 6 groups: control (CG), vehicle (VG) that received saline by orogastric gavage, a group exposed to formaldehyde 1% (FG) and formaldehyde exposed groups that received NAC at doses of 100, 150 and 200 mg/Kg (FN100, FN150 and FN200) for a period of 5 days...

NADPH oxidase 4 (NOX4) inhibition has been reported to mitigate diabetes induced beta-cell dysfunction and improve survival in vitro , as well as counteract high fat diet induced glucose intolerance in mice. We investigated the anti-diabetic effects of the selective NOX4 inhibitor GLX7013159 in vivo in athymic diabetic mice transplanted with human islets over a period of 4 weeks.The GLX7013159-treated mice achieved lower blood glucose and water consumption throughout the treatment period. Furthermore, GLX7013159 treatment resulted in improved insulin and c-peptide levels, better insulin secretion capacity, as well as in greatly reduced apoptotic rates of the insulin-positive human cells, measured as co-localization of insulin and cleaved caspase-3...

Mitophagy is a critical intracellular event during the progression of diabetic nephropathy (DN). Our previous study demonstrated that germacrone has anti-ferroptotic properties and is a potential therapeutic agent for DN. However, the relationship among germacrone, mitophagy, and ferroptosis in DN remains unclear. In this study, the data confirmed that germacrone ameliorates high glucose (HG)-induced ferroptosis through limiting Fe (2+) content and lipid reactive oxygen species (ROS) accumulation in human kidney 2 (HK-2) cells...

Age-related macular degeneration (AMD) is one of an increasing number of diseases that causes irreversible impairment and loss of vision in the elderly. AMD occurs by oxidative stress-mediated apoptosis of retinal pigment epithelium cells. The onset of AMD may be positively correlated with the exposure to blue light. We screened food-derived carotenoids for cytoprotective action against blue light irradiation using human ARPE-19 retinal pigment epithelium cells. This study revealed that blue light irradiation triggered apoptosis and oxidative stress in all- trans -retinal (atRAL)-exposed ARPE-19 cells by generating singlet oxygen (1 O2 ), leading to significant cell death...

A new approach to attenuating pathological inflammatory reactions by buffering the eicosanoid pathways with oxidation-resistant hexadeuterated arachidonic acid (D-ARA) is discussed. Enzymatic processing of ARA, released by phospholipase A2, by lipoxygenases, cyclooxygenases, and cytochromes yields a wide range of bioactive eicosanoids, including pro-inflammation, pro-angiogenesis and pro-thrombosis species that, when produced in excess, are an underlying cause of pathology. Conversely, some products of ARA oxidation possess pro-resolving properties...

Individuals with sickle cell disease (SCD) are at greater risk of rhabdomyolysis, a potentially life-threatening condition resulting from the breakdown of skeletal muscle fibers. Acute kidney injury (AKI) is one of the most severe complications of rhabdomyolysis. Chronic kidney and cardiovascular disease, which account for SCD mortality, are long-term consequences of AKI. Although SCD elevates the risks of rhabdomyolysis-induced sudden death, the mechanisms that underlie rhabdomyolysis-induced AKI in SCD are unclear...

To investigate the cross-sectional and longitudinal correlation between serum superoxide dismutase (SOD) levels and thyroid function with obesity before and after laparoscopic sleeve gastrectomy (LSG). Patients with morbid obesity ( n  = 219, 112 males and 107 females) who underwent LSG were selected and they were subdivided into normal levels of SOD (NSOD, n  = 112) and high levels of SOD (HSOD, n  = 107) according to the median value of SOD levels (183 U/mL)...

Oxidative stress is believed to be a major cause of injury after cardiac arrest (CA). While the effects of ROS generated within tissues have been extensively investigated, the potential of plasma-generated ROS in contributing to CA pathology has not been examined. We utilized Amplex Red (AR) to measure the real time-generation of ROS in isolated plasma from human CA patients. We first used post-CA rat plasma to identify interfering factors for AR oxidation, and then applied this knowledge to analyze human plasma samples, accounting for the identified confounders...

Myocardial ischemia/reperfusion injury (MIRI) is the principal cause of death and occurs after prolonged blockage of the coronary arteries. Diabetes represents one of the main factors aggravating myocardial injury. Restoring blood flow is the first intervention against a heart attack, although reperfusion process could cause additional damage, such as the overproduction of reacting oxygen species (ROS). In recent years, açaí berry has gained international attention as a functional food due to its antioxidant and anti-inflammatory proprieties; not only, this fruit has shown glucose-lowering effects...

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 15 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60 , DMBA, and Fullerene C60 +DMBA. The rats in the DMBA and Fullerene C60 +DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60 , DMBA and Fullerene C60 +DMBA groups were administered with Fullerene C60 (1...

The presence of hydrogen peroxide along with ferrous iron produces hydroxyl radicals that preferably oxidize polyunsaturated fatty acids (PUFA) to alkyl radicals (L•). The reaction of L• with an oxygen molecule produces lipid peroxyl radical (LOO•) that collectively trigger chain reactions, which results in the accumulation of lipid peroxidation products (LOOH). Oxygenase enzymes, such as lipoxygenase, also stimulate the peroxidation of PUFA. The production of phospholipid hydroperoxides (P-LOOH) can result in the destruction of the architecture of cell membranes and ultimate cell death...

Inflammation is a defensive immune response to external stimuli. However, uncontrolled inflammation may cause potential damage to the host. Therefore, timely control of uncontrolled inflammation is particularly important. Previous studies have found that small molecules with antioxidant activity, such as peroxidase mimic enzymes, can inhibit the development of inflammation. DhHP-6 is a new peptide mimic of peroxidase previously designed by our laboratory. Here, we explored its anti-inflammatory activity in vitro and in vivo ...

Accumulating evidence attributes the role of aldose reductase (AR) in modulating ROS and inflammation which are the main factor responsible for cancer progression and drug resistance. Epalrestat is the only AR inhibitor being used in Asian countries. It did not make it to the markets of the USA and Europe due to marginal efficacy as an antioxidant and anti-inflammatory agent owing to difficulty reaching intracellular targets. In our previous studies, we attempted to synthesize the epalrestat analogs and reported that the compound 4-((Z)-5-((Z)-2-Cyano-3-phenylallylidene)-4-oxo-2-thioxothiazolidin-3-yl) benzoic acid named as NARI-29 has potent AR inhibition compared to epalrestat...

AbstractsBesides the profound role of proprotein convertase subtilisin/kexin type-9 (PCSK-9) in LDL-C regulation, its association with other metabolic complications cannot be disregarded. The co-existence of redox imbalance and inflammatory cascades has greatly reflected the etiology of hyperglycemia. Therefore, we studied the association of PCSK-9 with inflammation and oxidative stress biomarkers to predict its role in the prognosis of diabetes and its associated complications in the Indian population. This pilot study examined a total of n = 187 subjects: healthy controls (HC; n = 50), diabetic without complication (T2DM; n = 49), diabetic nephropathy (T2DM-N; n = 43), and diabetic dyslipidemic (T2DM-DL; n = 45) subjects...

Ferroptosis is a novel form of cell death, manifested by iron-dependent, non-apoptotic manner resulting from the intracellular accumulation of large clusters of reactive oxygen species (ROS) and lipid peroxides due to abnormal iron metabolism. Since the liver is the main organ of human body for storing iron, it is essential to perform in-depth investigation on the role and mechanistic basis of ferroptosis in the context of divergent liver diseases. We previously summarized the emerging role of ferroptosis among various liver diseases, however, the past few years have been a surge in research establishing ferroptosis as the molecular basis or treatment option...