Oxygen, Volume 4, Issue 1 (March 2024) – 7 articles

The mitochondrial electron transport chain (mETC) contains molecular targets of volatile general anesthetics (VGAs), which places individuals with mETC mutations at risk for anesthetic complications, as exemplified by patients with Leigh syndrome (LS). The Drosophila melanogaster homozygous mutant for ND-23, which encodes a subunit of mETC Complex I, replicates numerous characteristics of LS, including neurodegeneration, shortened lifespan, behavioral anesthetic hypersensitivity, and toxicity. The anesthetic phenotype of toxicity (lethality) is also observed in flies homozygous for mutations in other Complex I subunits. By contrast, mutations conferring sensitivity have not yet been identified for subunits of Complexes II–V. Furthermore, anesthetic phenotypes are thought to be recessive; that is, risk is not conferred by heterozygous mutations. However, at older ages, exposure of heterozygous mutant ND-23 flies to the VGA isoflurane in 75% oxygen (hyperoxia) results in toxicity. It is also unknown whether combinations of heterozygous mutations in different subunits of the mETC can result in anesthetic toxicity. Here, we show that, following exposure to isoflurane in hyperoxia, flies carrying heterozygous mutations in two Complex I subunits, ND-23 and ND-SGDH (NADH dehydrogenase (ubiquinone) SGDH subunit), had a level of anesthetic toxicity that exceeded the added toxicities of the individual heterozygous mutations. In addition, we show that flies heterozygous for two different alleles of the Complex II gene SdhB were susceptible to isoflurane/hyperoxia-induced anesthetic toxicity. Finally, a mutation in the SdhC subunit of Complex II of Caenorhabditis elegans resulted in isoflurane-induced mortality, supporting the role of Complex II in anesthetic toxicity. These data expand the landscape of mutations in the mETC that increase sensitivity to anesthetic toxicity. Full article

The objective of this study was to determine the optimal conditions for the recovery of bioactive and antioxidant compounds in aqueous solutions of Cistus creticus leaves and then employ the optimal extract for the enrichment of yogurt samples. The optimal conditions were established by a response surface methodology and were determined to be a liquid-to-solid ratio of 48 mL/g at 76 °C for 41 min. The optimum extract yielded TPC 157.17 mg GAE/g dw and TFC 2.38 mg QE/g dw, while FRAP and DPPH values were 1258.52 and 933.67 μmol AAE/g dw, respectively. HPLC-DAD was utilized to identify and quantify specific polyphenols, like myricetin rhamnoside, in the extract. The optimal extract was then added to yogurt desserts during their preparation at three different concentrations to study how the physicochemical characteristics of the yogurt, as well as the antioxidant capacity added during enrichment, were affected. Statistical analysis of the results was carried out in order to obtain more valid data. It seems that the most suitable concentration for yogurt fortification was 0.1% w/v of the extract as, at this concentration, the yogurts exhibited higher antioxidant capacity, and their physicochemical characteristics were improved. Full article

On the thirty-fifth anniversary of the first description of O₂-sensitive K⁺ channels in the carotid body chemoreceptors O₂ sensing remains a salient issue in the literature. Whereas much has been learned about this subject, important questions such as the identity of the specific K⁺ channel subtype(s) responsible for O₂ sensing by chemoreceptors and the mechanism(s) by which their activities are altered by hypoxia have not yet been definitively answered. O₂ sensing is a fundamental biological process necessary for the acute and chronic responses to varying environmental O₂ levels which allow organisms to adapt to hypoxia. Whereas chronic responses depend on the modulation of hypoxia-inducible transcription factors which determine the expression of numerous genes encoding enzymes, transporters and growth factors, acute responses rely mainly on the dynamic modulation of ion channels by hypoxia, causing adaptive changes in cell excitability, contractility and secretory activity in specialized tissues. The most widely studied oxygen-sensitive ion channels are potassium channels, but oxygen sensing by members of both the calcium and sodium channel families has also been demonstrated. Given the explosion of information on this topic, in this review, we will focus on the mechanisms of physiological oxygen chemotransduction by PO₂-dependent K⁺ channels, with particular emphasis on their function in carotid body chemoreceptor cells (CBCC) and pulmonary artery smooth muscle cells (PASMC), highlighting areas of consensus and controversy within the field. We will first describe the most well-established concepts, those reproduced in multiple laboratories, and then discuss selected observations or questions that remain unresolved, and that limit our progress in this field. Full article

Produced by photosynthesis, oxygen (O₂) is a fundamentally important gas in biological systems, playing roles as a terminal electron receptor in respiration and in host defence through the creation of reactive oxygen species (ROS). Hydrogen (H₂) plays a role in metabolism for some organisms, such as at thermal vents and in the gut environment, but has a role in controlling growth and development, and in disease states, both in plants and animals. It has been suggested as a medical therapy and for enhancing agriculture. However, the exact mode of action of H₂ in biological systems is not fully established. Furthermore, there is an interrelationship between O₂ and H₂ in organisms. These gases may influence each other’s presence in solution, and may both interact with the same cellular components, such as haem prosthetic groups. It has also been suggested that H₂ may affect the structures of some proteins, such as globins, with possible effects on O₂ movement in organisms. Lastly, therapies may be based on supplying O₂ and H₂ together, such as with oxyhydrogen. Therefore, the relationship regarding how biological systems perceive and respond to both O₂ and H₂, and the interrelationship seen are worth considering, and will be discussed here. Full article

Background: Sepsis is a severe and life-threatening condition triggered by a dysregulated response to infection, leading to organ failure and, often, death. The syndrome is expensive to treat, with survivors frequently experiencing reduced quality of life and enduring various long-term disabilities. The increasing understanding of RNA, RNA biology, and therapeutic potential offers an unprecedented opportunity to develop innovative therapy. Objective: This study is a scoping review focusing on pre-clinical studies of microRNA (miRNA)-based therapies for sepsis. Methodology: A scoping review. The search strategy identified papers published in PubMed until 15 October 2023, using the keywords (microRNA) AND (sepsis) AND (animal model). Inclusion criteria included papers that used either gain- or loss-of-function approaches, excluding papers that did not focus on microRNAs as therapy targets, did not include animal models, did not show organ failure-specific assessments, and focused on microRNAs as biomarkers. The PRISMA-ScR guideline was used in this study. Results: A total of 199 articles were identified that featured the terms “microRNA/miRNA/miR”, “Sepsis”, and “animal model”. Of these, 51 articles (25.6%) employed miRNA-based therapeutic interventions in animal models of sepsis. Of these, 15 studies extended their inquiry to include or reference human clinical data. Key microRNAs of interest and their putative mechanisms of action in sepsis are highlighted. Conclusions: The body of work examined herein predominantly addresses various dimensions of sepsis-induced organ dysfunction, supporting the emerging role of miRNAs as potential therapeutic candidates. However, nearly 5% of papers on miR-based therapy have been retracted over the past 5 years, raising important concerns regarding the quality and complexity of the biology and models for assessing therapeutic potential. Full article

A member of the Verbenaceae family, Aloysia citrodora, or lemon verbena, is a medicinal herb with antioxidant compounds. The aim of this study was to develop a green, optimized method for the bioactive compound (carotenoids, ascorbic acid, and polyphenols) extraction from lemon verbena leaves through response surface methodology (RSM). The bioactive compound recovery was shown to be significantly affected by the extraction technique (both with pulsed electric field and ultrasound-assisted extraction), along with an extraction solvent, based on partial least squares analysis. Consequently, the maximum polyphenol yield required a double-assisted extraction with a relatively low extraction duration (60 min) at a high temperature (80 °C), with a moderate-polarity extraction solvent (50% v/v ethanol). With the optimized method, the total polyphenol content (TPC) was measured at 175.03 mg gallic acid equivalents/g, whereas chromatographic analysis revealed that verbascoside was the most prevalent polyphenol (132.61 mg/g). The optimum extract provided a high antioxidant capacity through the measurements of FRAP (1462.17 μmol ascorbic acid equivalents (AAE)/g), DPPH (1108.91 μmol AAE/g), and H₂O₂ (1662.93 μmol AAE/g). Total carotenoids were measured at 499.61 μg/g, with ascorbic acid at 8.36 μg/g. Correlation analyses revealed a negative correlation of the latter compound with color coordinates. This study highlights the potential of lemon verbena leaves to be used in pharmaceutical and food industries. Full article