Antioxidant activity and protective effect of propolis against carbon tetrachloride-induced liver and kidney injury by modulation of oxidative parameters

Background and Aim: Propolis has a protective effect against cellular damage caused by toxic agents such as drugs, metals, xenobiotics, and chemicals. The aim of this study was to investigate the antioxidant activity and the effect of ethanolic extract of propolis on carbon tetrachloride (CCl4)-induced oxidative stress on kidney and liver injury in rat. Materials and Methods: The study quantified phenol, flavone, and flavonol in propolis and assessed antioxidant activity using 2, 2-diphenyl-1-picrylhydrazyl, ferric reducing antioxidant power, and molybdate. The investigators used four groups of rats to study the effect of propolis on CCl4-induced toxicity. Propolis extract was given orally (500 mg/kg) for 12 days, and CCl4 (1 mL/kg) was administered intraperitoneally on day 5 of the experiment. Blood and tissue samples of the liver and kidney were collected on day 13 to measure biochemical and oxidative parameters. The parameters included malondialdehyde (MDA), protein carbonyl formation (PCO), advanced oxidation protein products (AOPP), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), and ascorbic acid (AA). Biochemical parameters included liver enzymes, blood urea (BU), creatinine, and uric acid (UA). Results: CCl4 decreased antioxidant agents, including CAT, GPx, GSH, and AA in the liver and kidney tissues. The oxidative agents' levels, including MDA, PCO, and AOPP, increased by CCl4 compared to the control group. CCl4 increased liver enzymes, UA, BU, and creatinine in the blood samples. Propolis significantly alleviated liver and kidney function, improved antioxidant parameters, and decreased levels of oxidative agents. Conclusion: The data showed for the 1st time that Moroccan propolis has a protective effect against CCl4-induced kidney and liver toxicity by maintaining the activity of the antioxidant defense system, which was most likely due to its antioxidant activity.

Synthesis, Antioxidant activity and Structure-Activity Relationship of gallic hydrazones Analogues

A series of gallic acid hydrazones were designed and synthesized as new potential anti-oxidant agents. Most of these compounds are potent antioxidants. The strongest compounds are 11 and 15 (EC50: 6.42 μg·mL−1, 6.86 μg·mL−1, DPPH) and (EC50: 12.85μg·mL−1, 12.49μg·mL−1ABTS), more potent than the positive control Trolox. Furthermore, the promising compounds 11 and 15 exhibited very low cytotoxic activity against HEK293 cell (IC50 >56.4 µM). The SAR study revealed that the pattern of hydroxyl, methoxy and methyl substituents on the gallic hydrazones framework can increase the antioxidant properties of the prototype compounds. Moreover, the results also showed that the activity increased with the number of the groups and increased following hydroxyl > methoxy > methyl. Overall, the present study suggests that the designed compounds may serve as lead molecules for developing novel anti-oxidative agents in food industry.

Oxidative Stress as a Therapeutic Target in Amyotrophic Lateral Sclerosis: Opportunities and Limitations

Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) and Lou Gehrig’s disease, is characterized by a loss of the lower motor neurons in the spinal cord and the upper motor neurons in the cerebral cortex. Due to the complex and multifactorial nature of the various risk factors and mechanisms that are related to motor neuronal degeneration, the pathological mechanisms of ALS are not fully understood. Oxidative stress is one of the known causes of ALS pathogenesis. This has been observed in patients as well as in cellular and animal models, and is known to induce mitochondrial dysfunction and the loss of motor neurons. Numerous therapeutic agents have been developed to inhibit oxidative stress and neuroinflammation. In this review, we describe the role of oxidative stress in ALS pathogenesis, and discuss several anti-inflammatory and anti-oxidative agents as potential therapeutics for ALS. Although oxidative stress and antioxidant fields are meaningful approaches to delay disease progression and prolong the survival in ALS, it is necessary to investigate various animal models or humans with different subtypes of sporadic and familial ALS.

Kinetics and Mechanistic Studies of Photochemical and Oxidative Stability of Galaxolide

Studies on kinetics of galaxolide (HHCB) degradation under influence of UV, simulated sunlight and some advanced oxidation processes (H2O2, UV/H2O2, and Vis/H2O2) were conducted. Galaxolide appeared to be a photolabile compound. The first-order kinetics model was assumed for all studied processes. It was observed that basic pH favored HHCB degradation. The influence of natural matrices (river water and artificial sweat) on direct photolysis of HHCB was examined. It was stated that the process of the photodegradation proceeded slower at the presence of each matrix. HHCB lactone was identified using the GC-MS technique. The recorded chromatograms showed that apart from the lactone, other degradation products were formed that we could not identify. In order to deeper understand the HHCB degradation process, DFT calculations were performed. The results pointed out that OH radicals play a key role in HHCB decomposition, which mainly proceeds via H abstractions as well as OH additions. It follows from the calculations that the visible light is sufficient to initiate the advanced oxidation processes (AOPs) under the oxidative conditions, whereas UV irradiation is needed to start decay with no oxidative agents.

Illékony nitritszármazékok („popperek”) által okozott methaemoglobinaemia

Összefoglaló. A methaemoglobinaemia az oxigén szállítására képtelen methemoglobin szintjének kóros emelkedését jelenti a vérben, ami jelentős szöveti oxigénhiányt okozhat, súlyos, akár életveszélyes tünetekhez vezethet. Methaemoglobinaemiát számos, oxidáló hatású exogén anyag idézhet elő, ezek közé tartoznak a partidrogként használt alkil-nitritek, az ún. „popperek” is. A „poppereket” korábban „alacsony rizikójú” drogként tartották számon, azonban számos esetet közöltek, amikor súlyos, időnként fatális kimenetelű methaemoglobinaemiát okoztak. A folyadékok gőzének belélegzése euforizáló, szexuálisvágy-fokozó és simaizom-lazító hatású, ezért a „popperek” igen népszerűek a homo- és biszexuális férfiak körében, de fiatal felnőttek és tinédzserek is használják. A folyadékok szájon át való fogyasztása különösen veszélyes. A szerzők két esetet ismertetnek, amelyekben a „popperek” használatát követően methaemoglobinaemia alakult ki. Mindkét betegnél, a jó általános állapot mellett, centrális és perifériás cyanosis tüneteit észlelték. Az alkalmazás módja (inhaláció/lenyelés), a methaemoglobinaemia súlyossága (16,4% és 57%) és a terápia eltérő volt a két betegnél. Az első beteg oxigén adása és tüneti kezelés mellett gyógyult, a másodiknál antidotum (metilénkék) adására is szükség volt. Mindketten panaszmentesen távoztak a kórházból. A szerzők célja az volt, hogy felhívják a figyelmet az illékony alkil-nitrit-származékok által okozott methaemoglobinaemiára, annak felismerésére, kezelésére, és bemutassák azok kevésbé ismert szövődményeit is. Orv Hetil. 2021; 162(8): 306–313. Summary. Methemoglobinemia means the abnormally elevated level of methemoglobin in the blood, which is incapable of oxygen transport, accordingly it can cause significant tissue hypoxia, leading to severe or even life-threatening clinical symptoms. Several exogen oxidative agents can induce methemoglobinemia, including alkyl-nitrites which are also used as party drugs, the so-called ‘poppers’. The ‘poppers’ were previously considered ‘low-risk’ drugs, however, several cases have been published when they caused severe, sometimes fatal methemoglobinemia. Inhaling vapours from liquids has euphoric, smooth-muscle relaxing and aphrodisiac effects, therefore ‘poppers’ are extremely popular among gay and bisexual men but also used by young adults and teenagers. Oral consumption of the fluids is particularly dangerous. The authors present two cases when methemoglobinemia developed after ‘poppers’ usage. Both patients were in good general condition and symptoms of central and peripheral cyanosis were detected. The method of application (inhalation/ ingestion), the severity of methemoglobinemia (16,4% and 57%) and the treatment were different in the two patients. The first patient recovered with inhalation of oxygen and symptomatic treatment; the second patient required administration of antidote (methylene blue). Both patients left the hospital without complaints. The authors’ aim was to attract attention to methemoglobinemia caused by volatile alkyl-nitrites, its recognition, treatment and to present their lesser-known complications. Orv Hetil. 2021; 12(8): 306–313.

Remodeling of oxygen-transporting tracheoles drives intestinal regeneration and tumorigenesis

The Drosophila tracheal system, as the functional equivalent of mammalian blood vessels, responds to hypoxia and transports oxygen throughout the body. Although the signaling pathways involved in tracheal development and the hypoxic response are well-studied, how adult tracheae interact with their target tissues is largely unknown. Here we show that the tracheae that serve the adult intestine are dynamic and respond to enteric infection, oxidative agents, and the development of gut tumors with increased terminal branching. Increased tracheation is necessary for efficient damage-induced intestinal stem cell (ISC)-mediated midgut regeneration and sufficient to drive ISC proliferation in the absence of damage. Gut damage or tumors induce Hif-1α/Sima, which, in turn, stimulates tracheole branching via the FGF(Brachless/Bnl)/FGFR(Breathless/Btl) signaling cascade. Bnl/Btl signaling is required both in the intestinal epithelium and the tracheal system for efficient damage-induced tracheal remodeling and ISC proliferation. We show that chemical or Pseudomonas-generated ROS directly affect the trachea and are necessary for branching and intestinal regeneration. Similarly, tracheole branching and the resulting increase in oxygen supply are essential for tumor growth in the midgut. Thus, we have identified a novel mechanism of visceral tracheal-intestinal tissue communication, whereby oxidative damage and tumors induce neo-tracheogenesis in adult Drosophila. This process is reminiscent of cancer-induced neo-angiogenesis in mammals.

Diapause Termination and Postdiapause in Lygus hesperus (Heteroptera: Miridae)

The western tarnished plant bug, Lygus hesperus Knight, overwinters as a diapausing adult in response to short day lengths. Once environmental conditions are favorable, the bugs revert to an active reproductive state. To determine the impact on life-history traits of diverting resources toward diapause rather than oogenesis during early adulthood, diapausing and nondiapausing L. hesperus females were reared from the same cohorts. Body mass, ovarian maturation, ovipositional activity, and survivorship were monitored starting either at the time of release from diapause-inducing conditions or at adult eclosion for diapausers and nondiapausers, respectively. Females that had gone through 2 wk of diapause were larger and able to mobilize the resources necessary for oogenesis faster than nondiapausers, initiating oogenesis and ovipositing sooner and at a faster initial rate. However, lifetime egg production and average daily rates were similar for both groups. Postdiapausers lived longer than nondiapausers by an average of 19 d, which is five more than the 2-wk period when they were reproductively senescent. Overall, the results indicate that short-term diapause does not have a negative impact on life history. Furthermore, the extra endogenous resources stored during diapause may be able to enhance the alacrity with which the female can take advantage of improved environmental conditions and may prolong life by shielding the females against environmental stressors such as temperature extremes, oxidative agents, or food deficits.

Vulnerabilities of the SARS-Cov-2 Virus to Proteotoxicity – Opportunity for Repurposed Chemotherapy of COVID-19 Infection

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 Coronavirus, has produced an urgent requirement and search for improved treatments whilst effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: Reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. We examined activated arginine residues in functional domain with predicted low pKa by neighboring group interaction in the SARS-CoV-2. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-COV and MERS. We also screened and identified drugs, which increase cellular MG concentration to virucidal levels and found two antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel were the best candidate for repurposing. Our findings provide evidence of potential vulnerability of SARS-CoV2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.