Oxidative Medicine and Cellular Longevity

Hyperoxia is essential to manage in preterm infants but causes injury to immature kidney. Previous study indicates that hyperoxia causes oxidative damage to neonatal kidney and impairs renal development. However, the underlying mechanisms by which neonatal hyperoxia effects on immature kidney still need to be elucidated. Tight junction, among which the representative proteins are claudin-4, occludin, and ZO-1, plays a crucial role in nephrogenesis and maintaining renal function. Inflammatory cytokines are involved in the pleiotropic regulation of tight junction proteins. Here, we investigated how neonatal hyperoxia affected the expression of key tight junction proteins and inflammatory factors (IL-6 and TNF-α) in the developing rat kidneys and elucidated their correlation with renal injury. We found claudin-4, occludin, and zonula occludens-1 (ZO-1) expression in proximal tubules was significantly downregulated after neonatal hyperoxia. The expression of these tight junction proteins was positively correlated with that of IL-6 and TNF-α, while claudin-4 expression was positively correlated with injury score of proximal tubules in mature kidneys. These findings indicated that impaired expression of tight junction proteins in kidney might be a potential mechanism of hyperoxia-induced nephrogenic disorders. It provides new insights to further study oxidative renal injury and development disorders and will be helpful for seeking potential therapeutics for hyperoxia-induced renal injury in the future.

Cancer is a major disease burden worldwide. In recent years, in addition to surgical resection, radiotherapy and chemotherapy are recognized as the most effective methods for treating solid tumors. These methods have been introduced to treat tumors of different origins and stages clinically. However, due to insufficient blood flow and oxygen (O₂) supply in solid tumors, hypoxia is caused, leading to decreased sensitivity of tumor cells and poor therapeutic effects. In addition, hypoxia will also lead to resistance to most anticancer drugs, accelerate malignant progress, and increase metastasis. In solid tumors, adequate O₂ supply and adequate delivery of anticancer drugs are essential to improve radiotherapy and chemotherapy sensitivity. In recent decades, the researches on relieving tumor hypoxia have attracted researchers’ extensive attention and achieved good results. However, as far as we know, there is no detailed review of the researches on alleviating tumor hypoxia. Therefore, in this contribution, we hope to give an overview of the researches on methods to improve tumor hypoxia environment and summarize their effect and application in tumor therapy, to provide a methodological reference for the research and development of new antitumor agents.

Ferroptosis is a recently discovered iron-dependent form of oxidative programmed cell death distinct from caspase-dependent apoptosis. In this study, we investigated the effect of ferroptosis in neomycin-induced hair cell loss by using selective ferroptosis inhibitor liproxstatin-1 (Lip-1). Cell viability was identified by CCK8 assay. The levels of reactive oxygen species (ROS) were determined by DCFH-DA and cellROX green staining. The mitochondrial membrane potential () was evaluated by TMRM staining. Intracellular iron and lipid peroxides were detected with Mito-FerroGreen and Liperfluo probes. We found that ferroptosis can be induced in both HEI-OC1 cells and neonatal mouse cochlear explants, as evidenced by Mito-FerroGreen and Liperfluo staining. Further experiments showed that pretreatment with Lip-1 significantly alleviated neomycin-induced increased ROS generation and disruption in in the HEI-OC1 cells. In parallel, Lip-1 significantly attenuated neomycin-induced hair cell damage in neonatal mouse cochlear explants. Collectively, these results suggest a novel mechanism for neomycin-induced ototoxicity and suggest that ferroptosis inhibition may be a new clinical intervention to prevent hearing loss.

Autism has been associated with a low antioxidant defense mechanism, while honey has been known for decades for its antioxidant and healing properties. Determination of stingless bee honey (KH) effects on antioxidant enzyme activities and oxidative damage in Autism Lymphoblastoid Cell Line (ALCL) was performed. ALCL and its normal sibling pair (NALCL) were cultured in RPMI-1640 medium at 37°C and 5% CO₂. ALCL was treated with 400 μg/mL KH (24 h), and oxidative stress marker, malondialdehyde (MDA), and antioxidant enzyme activities (catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured via enzyme-linked immunosorbent assay (ELISA), while deoxyribonucleic acid (DNA) damage was determined via comet assay. Low SOD activity () and high MDA level () were observed in ALCL compared to NALCL. Higher grade (Grades 2 and 3) of DNA damage was highly observed () in ALCL compared to NALCL, whereas lower grade (Grades 0 and 1) DNA damage was highly detected () in NALCL compared to ALCL. KH treatment caused a significant increase in SOD and GPx activities () in ALCL compared to untreated ALCL. Correspondingly, KH treatment reduced the Grade 2 DNA damage () in ALCL compared to untreated ALCL. CAT activity showed no significant difference between all three groups, while the MDA level showed no significant difference between treated and untreated ALCL. In conclusion, KH treatment significantly reduced the oxidative stress in ALCL by increasing the SOD and GPx antioxidant enzyme activities, while reducing the DNA damage.

The formation of reactive oxygen species (ROS) by the myeloid cell NADPH oxidase NOX2 is critical for the destruction of engulfed microorganisms. However, recent studies imply that ROS, formed by NOX2⁺ myeloid cells in the malignant microenvironment, exert multiple actions of relevance to the growth and spread of neoplastic cells. By generating ROS, tumor-infiltrating myeloid cells and NOX2⁺ leukemic myeloid cells may thus (i) compromise the function and viability of adjacent cytotoxic lymphocytes, including natural killer (NK) cells and T cells, (ii) oxidize DNA to trigger cancer-promoting somatic mutations, and (iii) affect the redox balance in cancer cells to control their proliferation and survival. Here, we discuss the impact of NOX2-derived ROS for tumorigenesis, tumor progression, regulation of antitumor immunity, and metastasis. We propose that NOX2 may be a targetable immune checkpoint in cancer.

In the present study, we investigated the potential of opuntiol, isolated from Opuntia ficus-indica, against UVA radiation-mediated inflammation and skin photoaging in experimental animals. The skin-shaved experimental mouse was subjected to UVA exposure at the dosage of 10 J/cm² per day for ten consecutive days (cumulative UVA dose: 100 J/cm²). Opuntiol (50 mg/kg b.wt.) was topically applied one hour before each UVA exposure. UVA (100 J/cm²) exposure induces epidermal hyperplasia and collagen disarrangement which leads to the photoaging-associated molecular changes in the mouse skin. Opuntiol pretreatment prevented UVA-linked clinical macroscopic skin lesions and histological changes in the mouse skin. Further, opuntiol prevents UVA-linked dermal collagen fiber loss in the mouse skin. Short-term UVA radiation (100 J/cm²) activates MAPKs through AP-1 and NF-κB p65 transcriptional pathways and subsequently induces the expression of inflammatory proteins and matrix-degrading proteinases in the mouse skin. Interestingly, opuntiol pretreatment inhibited UVA-induced activation of iNOS, VEGF, TNF-α, and COX-2 proteins and consequent activation of MMP-2, MMP-9, and MMP-12 in the mouse skin. Moreover, opuntiol was found to prevent collagen I and III breakdown in UVA radiation-exposed mouse skin. Thus, opuntiol protects mouse skin from UVA radiation-associated photoaging responses through inhibiting inflammatory responses, MAPK activation, and degradation of matrix collagen molecules.