Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe最新文献

In contemporary society, humans are susceptible to various radiation-borne hazards, including exposure to therapeutic modalities using low-linear energy transfer (low-LET) radiations (X-rays and γ-rays), natural high-LET radiation sourced from cosmic rays, as well as nuclear accidents such as the Fukushima Daiichi Nuclear Power Plant incident. Therefore, this threat incites an imminent necessity to develop novel radioprotective agents against a wide range of LET radiation and elucidate the underlying molecular mechanisms. This study aimed at assessing the radioprotectivity of Piceatannol (PIC), a potent antioxidant polyphenol present in abundance in passion fruit, by investigating its effects on radiation-induced reactive oxygen species (ROS) production and the consequent DNA double-strand break (DSB) capacity and cellular senescence. Specifically, total ROS was evaluated by DCFDA staining, mitochondrial superoxide by MitoSOX staining, DSB by γ-H2AX immunostaining, and cellular senescence by Senescence-associated-β-galactosidase staining.

The results demonstrated that PIC administration prior to exposure to both X-ray and high-LET radiation impeded radiation-induced DSB by suppressing ROS production. Interestingly, post-irradiation PIC treatment did not alter ROS levels but enhanced the efficiency of Ataxia Telangiectasia Mutated (ATM)-mediated DSB repair. Additionally, post-irradiation PIC treatment diminished senescence-associated beta-galactosidase levels, indicating that it hinders cellular senescence.

Conclusively, PIC exerts radioprotective effects against a wide range of LET radiation. The study findings validate the potential application of PIC not only as a radical scavenger but also as a novel DSB repair-activating radioprotective agent.

Phytochemicals are bioactive compounds derived from plants, renowned for their therapeutic potential. This study explores their pivotal roles in therapy and drug development, focusing on their interactions with crucial Signaling pathways and biological processes. Phytochemicals such as curcumin from turmeric, resveratrol from grapes, and epigallocatechin gallate (EGCG) from green tea, exert their effects primarily by modulating key pathways like PI3K/AKT, MAPK-ERK, Wnt, and Hedgehog, which are integral to cellular functions and disease progression. Phytochemicals like curcumin demonstrate potent anticancer activities by inhibiting proteins involved in cell proliferation, inducing apoptosis, and suppressing angiogenesis. Phytochemicals such as resveratrol also exhibit anti-inflammatory properties by targeting cytokine production and oxidative stress pathways, thereby alleviating chronic inflammatory conditions implicated in various diseases. Their (eg. EGCG's) antioxidant capabilities help neutralize free radicals and reduce oxidative damage, contributing to cellular health and longevity. Moreover, phytochemicals play a pivotal role in metabolic disorders such as diabetes and obesity by regulating glucose metabolism, lipid profiles, and insulin sensitivity. They also show promise in neurodegenerative diseases by protecting neuronal cells, enhancing cognitive functions, and potentially mitigating neuroinflammation and oxidative stress. For instance, berberine, an alkaloid found in several plants, shows promise in regulating glucose levels and improving insulin sensitivity. Additionally, ginsenosides from ginseng are known to protect neuronal cells, enhance cognitive functions, and potentially mitigate neuroinflammation and oxidative stress in neurodegenerative diseases. Despite their promising therapeutic benefits, challenges remain, particularly in ensuring bioavailability and standardization of phytochemical extracts for clinical use. Advances in screening techniques and formulation strategies aim to enhance their efficacy and integration into modern therapeutic approaches. Their multifaceted roles in modulating cellular processes underscore their importance as potential alternatives or complements to traditional pharmacotherapies, driving innovation in drug development and personalized medicine.

Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the absence of two such cysteine-rich Cx₉C-Cx₁₀C proteins, cytochrome c oxidase subunit 12 (Cox12) or cytochrome c oxidase assembly factor 6 (Coa6), Saccharomyces cerevisiae cells become sensitive under the oxidative and nitrosative stress. Interestingly, knockout of COX12 generates a significant amount of endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) as evidenced by FACS analysis. Moreover, cellular redox status, redox-active enzymes glutathione reductase, catalase, S-nitroso glutathione reductase, and protein nitration were significantly affected in Cox12 null cells. Further, we found that an overexpression of COX12 partially protects mitochondrial respiratory subunit Sdh2 under oxidative and nitrosative stress. Taken together, we provide proof of evidence that cysteine-rich proteins in the IMS dynamically control the cellular redox milieu and actively prevent reactive nitrogen and oxygen species generation.

Cervical cancer, a major global health issue and the fourth most common cancer among women, is strongly linked to Human Papillomavirus (HPV) infection. Emerging evidence indicates that oxidative stress plays a critical role in the carcinogenesis of cervical tissue. This study investigates the relationship between oxidative stress markers—specifically oxysterols, lipid oxidation, and protein carbonylation—and the progression of cervical neoplasia.

Oxysterols, which are elevated in various inflammatory diseases and cancers, were measured in cervicovaginal fluid samples using LC-MS/MS. The targeted oxysterols included 27-hydroxycholesterol (27-OHC), 7β-hydroxycholesterol (7β-OHC), 7-ketocholesterol (7-KC), and 7α,27-dihydroxycholesterol (7α,27-diOHC). Among these, 7α,27-dihydroxycholesterol was significantly increased in correlation with the severity of neoplastic stages. In parallel, protein carbonylation, an indicator of cellular oxidative stress, was assessed. Results revealed higher levels of protein carbonylation in neoplastic samples compared to non-neoplastic controls. These modifications were further analysed through redox proteomics to identify the specific proteins affected.

The study demonstrates that elevated lipid oxidation and protein carbonylation in cervicovaginal secretions are linked to the development and progression of cervical cancer. Identifying these biomarkers may improve screening strategies, enabling the identification of individuals at increased risk for cervical neoplasia and guiding timely interventions.

Chromium (Cr) is one of the most prevalent and potentially hazardous heavy metal found in the environment that can cause carcinogenic, genotoxic, and organ-specific irreversible complications. The most severe adverse outcome of Cr on humans involves oxidative stress. Melatonin was evidenced to alleviate such stress with various mechanisms including antioxidative potential and metal chelation. Male Wistar rats were divided into 4 groups and treated for 14 days. The first group (control) was treated with vehicle; the second group was orally administered with melatonin (20 mg/kg b.w./day); the third group was injected with sodium dichromate dihydrate (5 mg/kg bw, s.c. every alternate day); and the fourth group was administered with melatonin, 30 min before Cr administration. The treatment of rats with Cr (VI) was found to affect the metabolic pathways by altering the activities of enzymes possibly through uncompetitively binding with them. The current study also demonstrated that melatonin efficiently preserved the glucose levels and blood lipid profile. Moreover, melatonin was further found to protect the activities of glycolytic, Krebs’ cycle, and ETC enzymes. Further, melatonin pre-treatment reduced the production of $O_2^{.-}$ anion free radical and Ca²⁺ overload to protect the mitochondria at the ultrastructural level and reduced DNA damage to some extent. Therefore, this research strongly recommends melatonin as a therapeutic molecule against Cr-induced oxidative stress-mediated liver, heart, and kidney disorders.

Background

Targeting mitochondrial oxidative stress can be a promising strategy for the prevention of hepatocellular carcinoma (HCC). In the current study, we investigated the modulatory effect of mitochondria-targeted antioxidant, mitoQ against N-nitrosodiethylamine (NDEA)-induced hepatic damage in mouse.

Methods

BALB/c mice were administered NDEA (10 mg/kg b. w., single dose, intraperitoneally) and the hepatoprotective effect of mitoQ was studied by administering mitoQ (0.125 mg/kg b. w., orally once a week) to the animals. The administration of mitoQ started two weeks prior the NDEA administration. The animals were sacrificed 24 h following NDEA administration after which the blood samples and hepatic tissues were collected. Serum was used for the estimation of liver injury markers and hepatic tissues were analyzed for histopathological changes, antioxidant defense status, mitochondrial functional status, level of mitochondrial reactive oxygen species (mtROS) and mitochondrial lipid peroxidation (mtLPO).

Results

MitoQ treatment to the NDEA-challenged group normalized liver injury markers, level of mtROS and mtLPO. MitoQ treatment also improved the status of mitochondrial antioxidant defense system, mitochondrial complex enzymes.

Conclusion

Our findings indicate that mito-Q significantly protected against NDEA-induced hepatic damage by modulating mitochondrial function and redox status which may be one of the causes of its purported chemopreventive effect.

Congenital heart disease (CHD) represents a prevalent and diverse set of clinical conditions with significant morbidity and mortality. A recent meta-analysis indicates elevated oxidative stress levels in CHD patients compared to healthy controls. This review aims to elucidate the precise role of oxidative stress and its contributors in CHD. A systematic search of English-language publications on PubMed and the TRIP database yielded 29 reports analyzing oxidative stress markers in peripheral blood samples from pediatric and adult CHD populations. Only studies comparing oxidative stress markers either against controls, within CHD groups, or assessing oxidative stress markers over time evaluating the effect of an antioxidant treatment were included, followed by bias risk assessment. The different markers assessing oxidative stress in CHD were summarized, with scrutiny on potential influencing factors. Although findings are inconclusive overall, factors like cyanosis, genetic predispositions, and metabolic status emerge as important contributors. Additionally, multiple studies suggest a correlation between oxidative stress and CHD severity. Notably, no antioxidant therapies have been evaluated for reducing oxidative stress in CHD patients to date. Further research is imperative for a comprehensive understanding of CHD pathophysiology, particularly the heightened vulnerability of the right ventricle (RV) to heart failure (HF). Such insights could facilitate the development of tailored therapies for RV-related HF and dedicated antioxidant treatments, crucial for enhancing survival rates in this patient population.

It is well known that phyto-constituents possess hepatoprotective properties. The radical scavenging potential of catechin has received substantial research. The goal of the current study was to assess the beneficial effect of Catechin to safeguard rats from liver damage caused by isoniazid and rifampicin. In this investigation, Wistar rats were employed. Administration of isoniazid (100 mg/kg) with rifampicin (100 mg/kg) for 21 days caused hepatocellular injury. The dosages of catechin used were 25, 50, and 100 mg/kg body weight. Blood was drawn at the end of the study, and biochemical tests were performed to determine the enzyme levels. Restoration of AST, ALT, and ALP was brought about by catechin administration (25, 50, and 100 mg/kg body weight). The administration lead to in a restoration of the SOD and catalase levels. The expression of TNF-α, IL-1β, IL-6, MDA, and nitric oxide decreased. The findings prove that catechin had a significant hepatoprotective impact. The hepatoprotective action of catechin might be mediated by the radical scavenging and cytokine suppressing effects.

Prediabetes is a metabolic disorder marked by blood sugar levels that are elevated than usual but not yet high enough to be classified as type 2 diabetes. It is known that raised oxidative stress and insufficient antioxidant status play a role in the pathogenesis of type 1 and type 2 diabetes. In this study, we aimed to measure total oxidative stress and antioxidant status in prediabetic patients and compare them with healthy volunteers. Subjects with prediabetes according to their HbA1c and blood sugar levels in their routine tests were included in the study. The control group consisted of healthy volunteers who visited our clinics for routine health screening and had no health problems. TAS and TOS levels of the groups were compared. Mean TAS and median TOS values ​​were significantly different among study and control groups (p < 0.001 for both). Blood TOS level was a reliable risk factor of prediabetes, taking into account TAS, weight, triglycerides, and GFR. Higher oxidative stress and lower antioxidant levels were found in prediabetic patients compared to healthy ones. Diabetes development and related complications can be prevented by interventions for these markers in serum.