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Inhibition of aryl hydrocarbon receptor signaling and induction of NRF2-mediated antioxidant activity by cinnamaldehyde in human keratinocytes.

BACKGROUND: Dioxins and other environmental pollutants are toxic and remain in biological tissues for a long time leading to various levels of oxidative stress. Although the toxicity of these agents has been linked to activation of the aryl hydrocarbon receptor (AHR), no effective treatment has been developed. OBJECTIVE: To explore novel phytochemicals that inhibit AHR activation in keratinocytes. METHODS: Keratinocytes were used in this study because the skin is one of the organs most affected by dioxin and other environmental pollutants. HaCaT cells, which are a human keratinocyte cell lin

Somatosensory and vasomotor manifestations of individual and combined stimulation of TRPM8 and TRPA1 using topical L-menthol and trans-cinnamaldehyde in healthy volunteers.

BACKGROUND: Activation of TRPM8 and TRPA1 receptors generates cold and cold pain sensations, respectively, and is presumably important in clinical pain manifestations, such as cold hyperalgesia. This study investigated the interaction between TRPM8 and TRPA1 receptors through stimulation of glabrous human skin (volar forearm) by topical administration of 40% L-menthol and 10% trans-cinnamaldehyde (CA), individually and in combination. METHODS: Sensory manifestations were assessed in 10 healthy volunteers via a platform of 11 quantitative sensory (thermal and mechanical stimuli) and vasomotor

Cinnamaldehyde ameliorates STZ-induced rat diabetes through modulation of IRS1/PI3K/AKT2 pathway and AGEs/RAGE interaction.

Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder considered to be the most predominant form of diabetes throughout the world. This study aimed to investigate the possible effects of cinnamaldehyde (CIN) on insulin signaling pathways in STZ-induced T2D rat model. T2D was originated by feeding rats with a high-fat diet (HFD) plus 25% fructose solution plus streptozotocin (STZ) (35 mg/kg, i.p.). CIN effects were investigated on fasting blood glucose, insulin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), liver biomarkers, lipid profile, oxidative stress biomarker

The expression of surface markers on dendritic cells as indicators for the sensitizing potential of chemicals.

Novel approaches to testing of skin sensitizing chemicals have made use of immature dendritic cells (DCs) cultured from different hematopoietic progenitors. These cells resemble Langerhans cells (LCs), which are the most potent antigen presenting cells in the skin. Former research has focused on the phenotypic and functional changes of LCs after application of skin sensitizers. But it has proven difficult to isolate sufficient numbers of LCs from skin. This disadvantage is overcome by cultures of immature DCs providing high numbers of reactive cells. The aim of the present investigation was to

Cinnamaldehyde inhibits the progression of gastric cancer by regulating glycolysis through PTP1B/PI3K/AKT/mTOR signaling pathway.

Gastric cancer (GC) is a prevalent malignancy for which novel therapeutic approaches are urgently needed. Cinnamaldehyde (CA), a natural compound with anti-tumor potential, has an unclear mechanism of action in GC. This study aimed to investigate whether CA suppresses GC progression by modulating the PTP1B/PI3K/Akt/mTOR signaling pathway and its downstream glycolytic metabolism. The effects of CA on GC cell proliferation, migration, and invasion were evaluated through functional assays. Western blotting and metabolite detection were employed to analyze its impact on the PTP1B/PI3K/Akt/mTOR pat

The Protective Effects of Sesamin against Cyclophosphamide-Induced Nephrotoxicity through Modulation of Oxidative Stress, Inflammatory-Cytokines and Apoptosis in Rats.

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (

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… CP experiences metabolic activation through liver enzymes and forms 4-hydroxycyclophosphamide that further converts into two metabolites, acrolein and phosphoramide mustard, which is cytotoxic [ 28 ]. … Acrolein is an electrophilic and highly reactive aldehyde that interacts with the antioxidant defense system [ 29 ]. The acrolein can bind with reduced glutathione (GSH) and reduce its renal cell level. …

Charting the Current Landscape and Future Prospects of Cancer Therapy-Related Cardiovascular Toxicity in Cancer Survivors: From Bench to Bedside.

Cardio-oncology represents an emerging interdisciplinary discipline focusing on optimizing oncologic efficacy while mitigating treatment-related cardiovascular complications. The advent of novel anticancer agents such as targeted therapies, immune checkpoint inhibitors, and endocrine therapies has transformed cancer care, significantly improving survival rates. Nevertheless, prolonged patient survivorship has unmasked clinically significant cardiovascular sequelae, termed cancer therapy-related cardiovascular toxicity (CTR-CVT), which manifests as acute manifestations during therapy and delaye

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… , aldophosphamide, and 4-hydroxycyclophosphamide demonstrate intrinsic myocardial injury potential; of these, acrolein (an unsaturated and highly reactive aldehyde) exhibits the most pronounced cardiotoxic profile due to cardiomyocyte-selective vulnerability. 42 , 43 Mechanistically, acrolein induces … Acrolein can cause cardiovascular disease: a review. Cardiovasc Toxicol . 2017;17(3):227–236. doi: 10.1007/s12012-016-9396-5 44. Maeshima T, Honda K, Chikazawa M, et al. …

ДиметилФумарат Аттенуаты циклофосфамидозные повреждения мочевого пузыря и усиление цитотоксичной активности против клеток SH-SY5Y.

Острый кистит, вызванный циститом цилофосфамида (КХ), является изнурительной дисфункцией мочевого пузыря, которая, как правило, наблюдается у больных раком, главным образом в результате окислительных повреждений и воспаления тканей мочевого пузыря. Диметилфумарат (DMF) — эстер фумарной кислоты, утвержденный для лечения множественных склерозов в силу его антиоксидантов и противовоспалительных свойств. Таким образом, мы намеревались изучить многообразное воздействие ДМФ, включая как его потенциальное синергетическое воздействие с ХП на клетки SH-SY5Y, так и его незащищенное воздействие на острый

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… CP‐induced hemorrhagic cystitis originates from acrolein, an urotoxic metabolite accumulating in the bladder. … While the exact urotoxic etiology of acrolein is diverse, oxidative stress and inflammation are major contributors to the development of CP‐induced cystitis [ 33 ]. …

Antioxidant effects of Spirulina platensis (Arthrospira platensis) on cyclophosphamide-induced testicular injury in rats.

Cyclophosphamide (CP) is known to reduce fertility. The protective effects of Spirulina plantesis (SP) against CP-induced testicular toxicity were investigated. Male Wistar rats were categorized into eight groups (n = 7). Four groups of rats were administered CP at a dose of 5 mg in 5 mL distilled water kg-1 per day orally. Two of these groups were received SP (500 and 1000 mg kg-1 per day) orally after CP administration. One of these groups was also received vitamin E (100 mg kg-1 per day) intraperitoneally. A vehicle treated control group, two SP control groups (500 and 1000 mg kg-1 per day)

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… chronic and acute leukemia, lymphomas, multiple myeloma, bone marrow transplantation, rheumatic arthritis and some immune-related diseases. 1 The CP metabolism, by cytochrome p450 in the hepatocytes, generates active alkylating compounds such as 4-hydroxycyclo-phosphamide, aldophosphamide mustard and acrolein … Discussion The CP as an alkylating agent is the main cause of spermatogenesis dysfunction in cancer patients. 35 The CP metabolization by hepatic microsomal cytochrome P450, causes alkylating agents production such as 4-hydroxy-cyclophosphamide, aldophosphamide-mustard and acrolein. 2 Acrolein is a …

Нацеливание SMOX сохраняет оптический нерв Myelin, аксонская целостность и визуальные функции в мультиклерозе.

Множественный склероз (MS) — хроническое неврологическое состояние, затрагивающее молодых людей. Воспаление, обезвоживание и повреждение аксона являются ключевыми патологическими особенностями MS и его животной модели, экспериментального аутоиммунного энцефаломиелита (EAE). Наша предыдущая работа показала, что ингибирование сперматозоидной оксиды (SMOX) MDL72527, селективный необратимый фармакологический ингибитор, значительно сокращенные клинические симптомы, потеря клеток сетчатки (RGC) и воспаление зрительного нерва в мышах EAE. В настоящем исследовании изучался более широкий терапевтически

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… Similarly, elevated levels of acrolein are reported in MS patient samples and animal models [ 40 , 41 ]. … In our previous investigation, we observed changes in acrolein conjugates, a mediator of oxidative damage, in response to SMOX inhibition. It is worthwhile to explore whether acrolein contributes to the upregulation of Gal3 in EAE. These studies are under investigation. …

Study of Liposomes Containing Extract from the Leaves of Protium heptaphyllum (Aubl.) March in Animals Submitted to a Mutagenic Model Induced by Cyclophosphamide.

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage)

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… Cyclophosphamide is oxidized by P450 enzymes in the liver to become pharmacologically active, where it is converted to highly toxic metabolites—acrolein and phosphoramide mustard [ 45 ]—which induce oxidative stress and mutagenesis. … Molecular mechanisms of acrolein toxicity: Relevance to human disease. Toxicol. Sci. 2015;143:242–255. doi: 10.1093/toxsci/kfu233. 63. Nafees S., Rashid S., Ali N., Hasan S.K., Sultana S. …

Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy.

OBJECTIVE: To determine whether dietary compounds targeting NFE2-related factor 2 (Nrf2) activation can be used to attenuate renal damage and preserve renal function during the course of streptozotocin (STZ)-induced diabetic nephropathy. RESEARCH DESIGN AND METHODS: Diabetes was induced in Nrf2(+/+) and Nrf2(-/-) mice by STZ injection. Sulforaphane (SF) or cinnamic aldehyde (CA) was administered 2 weeks after STZ injection and metabolic indices and renal structure and function were assessed (18 weeks). Markers of diabetes including blood glucose, insulin, polydipsia, polyuria, and weight loss

TRPV1-mediated itch in seasonal allergic rhinitis.

BACKGROUND: Patients with allergic rhinitis may be abnormally sensitive to stimulation of the ion channel transient receptor potential vanilloid-1 (TRPV1). AIM OF THE STUDY: To examine effects of various TRP ion channel activators on sensory symptoms in allergic rhinitis prior to and during seasonal allergen exposure. METHODS: Nasal challenges were carried out with the TRPV1-activators capsaicin, anandamide and olvanil. Moreover, challenges were performed with mustard oil (allylisothiocyanate) and cinnamaldehyde as well as menthol, activators of TRPA1 and TRPM8, respectively. Nasal symptoms

Isopentenyl pyrophosphate is a novel antinociceptive substance that inhibits TRPV3 and TRPA1 ion channels.

Transient receptor potential ion channels (TRPs) expressed in the periphery sense and electrically transduce noxious stimuli to transmit the signals to the brain. Many natural and synthetic ligands for the sensory TRPs have been found, but little is known about endogenous inhibitors of these TRP channels. Recently, we reported that farnesyl pyrophosphate, an endogenous substance produced in the mevalonate pathway, is a specific activator for TRPV3. Here, we show that isopentenyl pyrophosphate (IPP), an upstream metabolite in the same pathway, is a dual inhibitor for TRPA1 and TRPV3. By using C

Transient receptor potential ankyrin 1 is expressed by inhibitory motoneurons of the mouse intestine.

BACKGROUND & AIMS: Transient receptor potential ankyrin (TRPA) 1, an excitatory ion channel expressed by sensory neurons, mediates somatic and visceral pain in response to direct activation or noxious mechanical stimulation. Although the intestine is routinely exposed to irritant alimentary compounds and inflammatory mediators that activate TRPA1, there is no direct evidence for functional TRPA1 receptors on enteric neurons, and the effects of TRPA1 activation on intestinal function have not been determined. We characterized expression of TRPA1 by enteric neurons and determined its involvement

Personal and ambient exposures to air toxics in Camden, New Jersey.

Personal exposures and ambient concentrations of air toxics were characterized in a pollution "hot spot" and an urban reference site, both i … maldehyde air pollution in summer. Personal concentrations of toluene (25.4 +/- 13.5 microg/m3) and acrolein (1.78 +/- 3.7 microg/m3) in Waterfront South were found to be higher than those in the Copewood-Davis neighborhood (13.1 +/- 15.3 microg/m3 for toluene and 1.27 +/- 2.36 microg/m3 for acrolein). However, personal concentrations for most of the other …

Oxidative Stress Linking Obesity and Cancer: Is Obesity a 'Radical Trigger' to Cancer?

Obesity is on the rise worldwide, and consequently, obesity-related non-communicable diseases are as well. Nutritional overload induces metabolic adaptations in an attempt to restore the disturbed balance, and the byproducts of the mechanisms at hand include an increased generation of reactive species. Obesity-related oxidative stress causes damage to vulnerable systems and ultimately contributes to neoplastic transformation. Dysfunctional obese adipose tissue releases cytokines and induces changes in the cell microenvironment, promoting cell survival and progression of the transformed cancer

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… Acrolein is another product of lipid peroxidation that has cancerogenic effects. Interchange DNA and protein DNA crosslinks formed as an acrolein effect were connected to cancers in several organs such as the liver, lung, and bladder [ 89 , 90 ]. … Interestingly, acrolein has the ability to interact with the lysine residues of H4’s newly formed histones that interfere with chromatin assembly [ 91 ]. 4. …

[Molecular Mechanisms of Huangjing Zanyu Capsule in Treating Oligoasthenospermia: A Study Based on AMPK-Mediated Mitophagy].

OBJECTIVE: To investigate the molecular mechanism of Huangjing Zanyu Capsule (HJZY), a new class-Ⅲ traditional Chinese medicine for the treatment of male infertility developed by Wang Qi, an academician of the Chinese Academy of Engineering, based on AMPK-mediated mitophagy in the treatment of oligoasthenospermia. METHODS: Acrolein (ACR) was used to treat GC-2spd(ts) mouse spermatocytes to establish a cell model of oligoasthenospermia. The optimal ACR concentration and exposure time for subsequent modeling were determined by CCK8 cell viability assay. After successful modeling, the cells were…

Связь между окисляющим стрессом, митохондриальной дисфункцией, железным метаболизмом и микроглией в множестве склерозов: обзор нарации.

В последние годы в патогенезе множественного склероза особое внимание уделяется митохондриальным процессам, влияющим на начало заболевания. Окисляющий стресс будет одним из последствий митохондриальной дисфункции, и его воздействие на ткани мозга хорошо описано. Микроглия, как макрофаж мозга, имеет важную функцию в удалении нежелательных метаболитов, а также железа, который является усилителем окислительного стресса. Существуют новшества с точки зрения связи между этими процессами, которые в большей степени перенаправляют исследования на сам процесс нейродегенерации, с тем чтобы больше не дела

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… In the presence of reduced metals and ascorbate, malonaldehyde, acrolein 4-hydroxy-2-nonenal and 4-hydroxy-2-hexenal are formed, which have a long half-life and can diffuse to distant sites. … Abbreviations: ↑—increased, ↓—decreased, NT—Nitrotyrosine, HNE—acrolein 4-hydroxy-2-nonenal, MDA—malonaldehyde, SOD—superoxide dismutase, CAT—catalase, NADH-2s—NADP quinone oxidoreductase and HO- heme oxygenase, UA—uric acid, GSH—glutathione, GR—glutathione reductase, GSHPx—glutathione peroxidase, NO …

Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, s

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… The chemical is activated by the hepatic P-450 cytochrome and its metabolites phosphoramide mustard and acrolein are linked to its antineoplastic and other toxic side effects [30] , [31] . CPA has been recommended to be used as a positive control chemical in genetic toxicity tests [32] , [33] . … In the first pathway, CPA is catalyzed by cytochrome P–4502 B and P-4502C enzymes to form the DNA cross- linking agent, phosphoramide mustard, and the toxic metabolite, acrolein (AC). …