Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Application of melatonin-mediated modulation of drought tolerance by regulating photosynthetic efficiency, chloroplast ultrastructure, and endogenous hormones in maize

Background Melatonin played an essential role in numerous vital life processes of animals and captured the interests of plant biologists because of its potent role in plants as well. As far as its possible contribution to photoperiodic processes, melatonin is believed to act as a growth regulator and a direct free radical scavenger/indirect antioxidant. The objective of this study to identify a precise melatonin concentration for a particular application method to improve plant growth requires identification and clarification. Methods This work establishes unique findings by optimizing melatonin concentration in alleviating the detrimental effects of drought stress in maize. Maize plants were subjected to drought stress (40–45% FC) after treatments of melatonin soil drenching at different concentrations (50, 100, and 150 µM) to consider the changes of growth attribute, chlorophyll contents, photosynthetic rate, relative water content (RWC), chloroplast ultrastructure, endogenous hormonal mechanism, and grain yield. Results Our results showed that the application of melatonin treatments remarkably improved the plant growth attributes, chlorophyll contents, photosynthetic rate, RWC, hormonal mechanism, and grain yield plant−1 under drought conditions at a variable rate. Conclusion Our current findings hereby confirmed the mitigating potential of melatonin application 100 µM for drought stress by maintaining plant growth, hormone content, and grain yield of maize. We conclude that the application of melatonin to maize is effective in reducing drought stress tolerance. Graphical Abstract

Single-Atom Fe-Anchored Nano-Diamond With Enhanced Dual-Enzyme Mimicking Performance for H2O2 and Glutathione Detection

Glutathione (GSH) is an important antioxidant and free radical scavenger that converts harmful toxins into harmless substances and excretes them out of the body. In the present study, we successfully prepared single-atom iron oxide-nanoparticle (Fe-NP)-modified nanodiamonds (NDs) named Fe-NDs via a one-pot in situ reduction method. This nanozyme functionally mimics two major enzymes, namely, peroxidase and oxidase. Accordingly, a colorimetric sensing platform was designed to detect hydrogen peroxide (H2O2) and GSH. Owing to their peroxidase-like activity, Fe-NDs can oxidize colorless 3,3′,5,5′-tetramethylbenzidine (TMB) into blue with sufficient linearity at H2O2 concentrations of 1–60 μM and with a detection limit of 0.3 μM. Furthermore, using different concentrations of GSH, oxidized TMB can be reduced to TMB, and the color change from blue to nearly colorless can be observed by the naked eye (linear range, 1–25 μM; detection limit, 0.072 μM). The established colorimetric method based on oxidase-like activity can be successfully used to detect reduced GSH in tablets and injections with good selectivity and high sensitivity. The results of this study exhibited reliable consistency with the detection results obtained using high-performance liquid chromatography (HPLC). Therefore, the Fe-NDs colorimetric sensor designed in this study offers adequate accuracy and sensitivity.

Pterostilbene Alleviates Chlorpyrifos-Induced Damage During Porcine Oocyte Maturation

Chlorpyrifos (CPF), a widely used organophosphate pesticide, is reported to severely impair mammalian reproductive system. Pterostilbene (PTS), an effective free radical scavenger, is considered as beneficial for mammalian reproduction. However, the toxicity of CPF on oocyte maturation and whether PTS can eliminate the detrimental effect of CPF on oocytes remain unclear. Here, porcine oocytes were applied to investigate the potential effect and possible mechanism of CPF and PTS during oocyte maturation. This work demonstrated that CPF significantly delayed the meiotic progression and decreased the polar body extrusion by disturbing spindle assembly and chromosome alignment and causing DNA damage in oocytes (p < 0.05). And, CPF significantly impaired oocyte cytoplasmic maturation by inducing the high level of reactive oxygen species and decreasing glutathione content (p < 0.05). Moreover, CPF significantly triggered embryo apoptosis and reduced the blastocyst rate and cell number following parthenogenetic activation (p < 0.05). Whereas CPF-exposed oocytes were treated with PTS, these defects caused by CPF were obviously rescued, and oocyte maturation and subsequent embryonic development were also significantly ameliorated (p < 0.05). In conclusion, these results revealed that CPF exerted the toxic effect on porcine oocytes, while PTS effectively alleviated CPF-induced damage on oocytes. This work provides a potential strategy to protect oocyte maturation in mammalian species.

Safranal Effect against Cyclophosphamide-Induced Liver Injury

The liver is the primary organ for drug metabolism, elimination, Cyclophosphamid is the classical alkylating agent nitrogen mustard, its metabolism into two cytotoxic metabolites, and increase reactive oxygen species that is make liver toxicity. Safranal as the most abundant chemical in saffron essential oil, it have anti-oxidant, anti-inflammatory, antiapoptic and free radical scavenger activity. The aim of study is to assess the protective effects of safranal on the cyclophosphamide-induce liver toxicity in rat model. This occur by using five different groups of rats; control group, treatment group, cyclophosamide group (intraperitoneal i.p), cyclophosamide and (50mg and 100mg) oral safranal treatment groups. This study showed this protective by decreasing liver parameter enzyme (aminotransferase enzyme) and MDA level, increases glutathione and NRF2

Naringenin Release to Biomembrane Models by Incorporation into Nanoparticles. Experimental Evidence Using Differential Scanning Calorimetry

Naringenin (4′,5,7-trihydroxyflavanone-7-rhamnoglucosideor naringenin-7-rhamnoglucoside), a flavonoid present in large quantities in citrus, has different beneficial effects on human health as an antioxidant, free radical scavenger, anti-inflammatory, carbohydrate metabolism promoter, and immune system modulator. Different studies have shown that this substance also has a hypoglycemic and antihypertensive effect, reduces cholesterol and triglycerides, and plays an important protective role in the heart tissue; moreover, it provides neuroprotection against various neurological disorders such as Parkinson’s disease and unpredictable chronic stress-induced depression. Despite these advantages, Naringenin is poorly absorbed, and the small percentage absorbed is rapidly degraded by the liver, as a result losing its activity. Several approaches have been attempted to overcome these obstacles, among them, nanotechnology, with the use of Drug Delivery Systems (DDS) as Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC). DDS can, in fact, improve the drug bioavailability. The aim of this study was to develop and characterize SLN and NLC containing Naringenin and to evaluate the ability of these nanoparticles to release Naringenin at the cell level using biomembrane models represented by Multilamellar Vesicles (MLV). These studies were performed using Differential Scanning Calorimetry, a powerful technique to detect the interaction of drugs and delivery systems with MLV. It was shown that Naringenin could be better incorporated into NLC with respect to SLN and that Naringenin could be released by NLC into the biomembrane model. Therefore, suggesting the administration of Naringenin loaded into nanoparticles could help avoid the disadvantages associated with the use of the free molecule.

Application of a free radical scavenger edaravone in patients with subarachnoid hemorrhage (review)

Background. The free radical scavenger edaravon helps to reduce the area of ischemic injury and improve the long-term effects of stroke and is therefore widely used in the treatment of ischemic stroke. However, the role of edaravone in the treatment of patients with subarachnoid hemorrhage has not yet been clarified. The purpose was to investigate the feasibility and effectiveness of the use of the free radical scavenger xavron (edaravon) in the treatment of patients with subarachnoid hemorrhage. Materials and methods. A search was conducted for studies and systematic reviews for the keywords: “acute stroke”; “subarachnoid hemorrhage”, “hemorrhagic transformation”, “edaravon” in the Google Scholar database published between 2003 and 2021. Results. The use of edaravone in patients with subarachnoid hemorrhage was accompanied by the activation of anti-inflammatory and reduction of pro-inflammatory peptides, activation of anti-apoptotic mechanisms, reduction of lipid peroxidation, oxidative trauma, the permeability of the brain swelling. Conclusions. The main effects of edaravon (xavron) have been found to reduce neurological deficits, accelerate the recovery of neurological disorders, and improve functional outcomes. Thus, the introduction of edaravone in patients with subarachnoid hemorrhage has been proven to be reliably effective and safe.

Celastrol and Melatonin Modify SIRT1, SIRT6 and SIRT7 Gene Expression and Improve the Response of Human Granulosa-Lutein Cells to Oxidative Stress

An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.

Evaluation of Betulinic Acid Effects on Pain, Anxiety, Catalepsy, and Oxidative Stress in Animal Model of Parkinson’s Disease.

BackgroundParkinson’s disease (PD) is known by motor impairments. Betulinic acid (BA) is a natural active compound with potent antioxidant activity. The present study addresses the question whether BA affects motor dysfunctions, pain, anxiety and molecular changes in the rat model of PD.MethodsRight medial forebrain bundle (MFB) was lesioned by injection of 6-OHDA in Male Wistar rats. BA (0.5, 5 & 10 mg/kg) and L-dopa (20 mg/kg) were administrated for 7 days. rigidity, anxiety, analgesia and memory, were assessed by bar test, open-field, elevated plus-maze (EPM), tail-flick and shuttle box. Additionally, the malondialdehyde (MDA), Superoxide dismutase (SOD), glutathione peroxidase (GPx) activity as well as Brain-derived neurotrophic factor (BDNF) and Interleukin 10 (IL10) levels in the brain tissue were measured.ResultsTreatment with BA significantly reversed the 6-OHDA-induced motor complication in the bar test, but it modified anxiety like behavior neither in open-field nor in EPM, it only decreased the time spent in open arms. Moreover no significant changes were found in the tail-flick between treatment and sham groups. On the other hand, the level of MDA & IL10 were decreased, and the activity of GPx, levels of SOD & BDNF in the rats brains were increased.ConclusionOur results showed that BA could affect as a potent natural free radical scavenger which removes brain tissue oxidants in PD. It can account a possible promise as a good therapeutic agent for motor and non-motor complications in PD.