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Due to the advantages of PVC membrane sensors based on ion carrier over the other analytical methods such as spectrophotometry, mass spectrometry, inductively coupled plasma atomic emission spectrometry, inductively coupled [...], The present paper describes the fabrication of a new polyvinylchloride (PVC) membrane electrode for the determination of Nd(III) ion based on 4-hydroxypyrrolidine-2-carboxylic acid (LHP) as an active material along with sodium tetraphenyl borate (NaTPB) as an anionic additive and acetophenone (AP) as solvent mediator. The optimum composition (%, w/w) of the best performing membrane contained 66 AP, 30 PVC, 2 NaTPB and 3 LHP. The basic analytical parameters of this electrode such as slope characteristics, detection limit, response time, selectivity and pH effect were assessed. The electrode displayed a Nernstian response in terms of slope (20.5 [+ or -] 0.4 mV per decade) and response time (~8 [+ or -] 1 s) over a wide neodymium ion concentration range of [10.sup.-6] to [10.sup.-2] M with a detection limit of 7.5 x [10.sup.-7] M. The potentiometric response of the electrode was constant in the pH range of 3.2-8.9. According to the selectivity coefficients determined by the matched potential method, the interference of many common alkaline, alkaline earth, transition, heavy metals and specially lanthanide ions in determination of Nd(III) ion was very low. The proposed electrode has been successfully used as an indicator electrode in the potentiometric titration of Nd(III) ion with EDTA and applied for determination of Nd(III) ion in mixtures of different ions. Keywords: neodymium, 4-hydroxypyrrolidine-2-carboxylic acid (LHP), PVC membrane, potentiometric, sensor, ion-selective electrode DOI: 10.1134/S1061934818010094

Objective: To compare the anti-arthritic potential of orally administered auraptene (AUR) and umbellliprenin (UMB) in chronic inflammation by exploring the differential effect on regulating TNF-α and IL-17., Methods & Materials: Sixty male rats were divided into ten groups, and after confirming chronic inflammation, the treatment groups received AUR or UMB orally for 9 days. On day 16, histopathological changes were evaluated. Altered serum levels of the inflammatory cytokines TNF-α and IL-17 were examined as the underlying mechanisms., Results: Administering AUR orally at 16 mM/kg caused a significant increase in body weight gain compared to the baseline (p < 0.05), while UMB at a dose of 64 mM/kg significantly reduced edema size (p < 0.01). TNF-α levels were significantly lower in all doses of AUR and UMB treatments compared to the arthritis control group (p < 0.05). Treatment with AUR at all relative doses resulted in a significant decrease in IL-17 levels compared to the arthritis control group (p < 0.05), whereas UMB treatment did not show a significant effect on IL-17 levels., Conclusion: AUR and UMB regulate TNF-α and IL-17 differently; AUR inhibits both, showing broad therapeutic potential, while UMB specifically targets TNF-α, showing a specialized role., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Cisplatin is a widely used chemotherapeutic agent for the treatment of various cancers. However, the clinical use of cisplatin is limited by its cardiotoxic side effects. The primary mechanisms implicated in this cardiotoxicity include mitochondrial dysfunction, oxidative stress, inflammation, and apoptotic. Numerous natural compounds (NCs) have been introduced as promising protective factors against cisplatin-mediated cardiac damage. The current review summarized the potential of various NCs as cardioprotective agents at the molecular levels. These compounds exhibited potent antioxidant and anti-inflammatory effects by interaction with the PI3K/AKT, AMPK, Nrf2, NF-κB, and NLRP3/caspase-1/GSDMD pathways. Generally, the modulation of these signaling pathways by NCs represents a promising strategy for improving the therapeutic index of cisplatin by reducing its cardiac side effects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Isoproterenol (ISO) usage is limited by its potential for cardiotoxicity. We sought to investigate the potential of agmatine in mitigating ISO-induced cardiotoxicity. Agmatine (100 mg/kg/day) was intraperitoneally administered to Wistar rats for 7 days in the presence or absence of cardiotoxicity induced by subcutaneous injection of ISO (85 mg/kg) on the sixth and seventh days. ECG parameters, lactate dehydrogenase (LDH), malondialdehyde (MDA), and creatinine phosphokinase (CPK) were investigated. Changes in cardiac tissue were also investigated using H&E staining. The heart weight/body weight ratio increased in ISO-treated rats. In the agmatine + ISO group, the increased heart rate observed in ISO-treated rats was reversed (317.2 ± 10.5 vs 452.2 ± 10.61, P < 0.001). Agmatine ameliorated the change in PR, RR, and ST intervals and the QRS complex, which was reduced by ISO. Treatment with saline, ISO, and agmatine had no significant effect on papillary muscle stimulation (P > 0.05). The administration of agmatine to ISO-receiving group could mitigate several parameters when compared to ISO-receiving group including increasing papillary muscle contraction (0.83 vs 0.71 N/M 2 respectively, P < 0.01), decreasing LDH levels (660 ng/ml vs 1080 ng/ml, respectively, P < 0.05), decreasing CPK levels (377 U/l vs 642 U/l, respectively, P < 0.05) and decreasing MDA levels (20.32 µM/l vs 46.83 µM/l, P < 0.001). Coadministration of agmatine and ISO is capable of ameliorating ISO cardiotoxicity by antioxidant effects and controlling the hemostasis of calcium in myocytes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiac diseases encompass a wide range of conditions that affect the structure and function of the heart. These conditions are a leading cause of morbidity and mortality worldwide. The serum- and glucocorticoid-inducible kinase 1 (SGK1) is a serine/threonine kinase that plays a significant role in various cellular processes, including cell survival and stress response. Alterations in SGK1 activity can have significant impacts on health and disease. Multiple research findings have indicated that SGK1 is associated with heart disease due to its involvement in cardiac hypertrophy and fibrosis. This article reviews different signaling pathways associated with SGK1 activity in various heart conditions, including the SGK1/NF-κB and PI3K/SGK1 pathways., Competing Interests: Declaration of Competing Interest “Serum and glucocorticoid-regulated kinase 1 (SGK1) as an emerging therapeutic target for cardiac diseases” that we would like to submit for publication as a review paper. All the authors have read, approved and made substantial contributions for the manuscript. None of the original material contained in this manuscript has been previously published nor is currently under review for publication elsewhere. Besides, authors declare no conflict of interests and/or commercial products or companies., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Computational toxicology utilizes computer models and simulations to predict the toxicity of chemicals. Bibliometric studies evaluate the impact of scientific research in a specific field., Methods: A bibliometric analysis of the computational methods used in toxicity assessment was conducted on the Web of Science between 1977 and 2024 February 12., Results: Findings of this study showed that computational toxicology has evolved considerably over the years, moving towards more advanced computational methods, including machine learning, molecular docking, and deep learning. Artificial intelligence significantly enhances computational toxicology research by improving the accuracy and efficiency of toxicity predictions., Conclusion: Generally, the study highlighted a significant rise in research output in computational toxicology, with a growing interest in advanced methods and a notable focus on refining predictive models to optimize drug properties using tools like pkCSM for more precise predictions., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cisplatin is a chemotherapeutic that dose-dependently causes renal complications such as decreased kidney function and acute kidney injury. The endoplasmic reticulum (ER) is responsible for calcium homeostasis and protein folding and plays a major part in cisplatin's nephrotoxicity. The current article reviews how chemical and natural compounds modulate cisplatin-induced apoptosis, autophagy, and inflammation by inhibiting ER stress signaling pathways. The available evidence indicates that natural compounds (Achyranthes aspera water-soluble extract, morin hydrate, fucoidan, isoliquiritigenin, leonurine, epigallocatechin-3-gallate, grape seed proanthocyanidin, and ginseng polysaccharide) and chemicals (Sal003, NSC228155, TUG891, dorsomorphin (compound C), HC-030031, dexmedetomidine, and recombinant human erythropoietin (rHuEpo)) can alleviate cisplatin nephrotoxicity by suppression of ER stress signaling pathways including IRE1α/ASK1/JNK, PERK-eIF2α-ATF4, and ATF6, as well as PI3K/AKT signaling pathway. Since ER and related signaling pathways are important in cisplatin nephrotoxicity, agents that can inhibit the abovementioned signaling pathways may hold promise in alleviating this untoward adverse effect., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Doxorubicin (DOX) is a chemotherapy drug known to induce metabolic changes in the heart, leading to potential heart toxicity. These changes impact various cellular functions and pathways such as disrupting the mechanistic target of rapamycin (mTOR) signaling pathway. The study aimed to investigate the effect of DOX on the mTOR pathway through an in vivo systematic review. Databases were searched on September 11, 2023. We finally included 30 in vivo studies that examined the mTOR expression in cardiac tissue samples. The present study has shown that the PI3K/AKT/mTOR, the AMPK/mTOR, the p53/mTOR signaling, the mTOR/TFEB pathway, the p38 MAPK/mTOR, the sestrins/mTOR, and the KLF15/eNOS/mTORC1 signaling pathways play a crucial role in the development of DOX-induced cardiotoxicity. Inhibition or dysregulation of these pathways can lead to increased oxidative stress, apoptosis, and other adverse effects on the heart. Strategies that target and modulate the mTOR pathways, such as the use of mTOR inhibitors like rapamycin, have the potential to enhance the anticancer effects of DOX while also mitigating its cardiotoxic side effects., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Doxorubicin is a potent chemotherapeutic agent that can cause cardiotoxicity. Many documents (more than 14,000) have been published in the area of doxorubicin-induced cardiotoxicity (DIC) since 1970. A comprehensive bibliographic analysis of author keywords was used to describe better and understand the molecular mechanisms involved in DIC. The objective was to consider the state of the author keywords of research on the molecular mechanisms involved in DIC based on a bibliometrics study of articles published over the past fifty years. A bibliometrics analysis was conducted using VOSviewer with data collected from the Web of Science Core Collection database of over 14,000 documents (from 1970 to July 19, 2023). Using scientific publications retrieved about DIC, author keywords were assessed at the scientific field level. The current study showed that the annual number of DIC-related publications has increased over the past 50 years. The Journal of Clinical Oncology is the leading journal in this field. The top cited DIC document was published in 2004. The top keywords with high frequency were "doxorubicin," "cardiotoxicity," and "adriamycin." According to the results of this study, the most common mechanisms involved in DIC were as follows oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis. The highest occurrences of regulators-related author keywords were "AKT," "Sirt1," and "AMPK." Based on the findings, oxidative stress, apoptosis, inflammation, autophagy, mitophagy, endoplasmic reticulum stress, pyroptosis, and ferroptosis were hot research mechanisms of DIC from 1970 to July 19, 2023., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Doxorubicin (DOX) is commonly used for the treatment of various types of cancer, however can cause serious side effects, including cardiotoxicity. The mechanisms involved in DOX-induced cardiac damage are complex and not yet fully understood. One mechanism is the disruption of cardiac metabolism, which can impair cardiac function. The mammalian target of rapamycin (mTOR) is a key regulator of cardiac energy metabolism, and dysregulation of mTOR signaling has been implicated in DOX-induced cardiac dysfunction. Natural compounds (NCs) have been shown to improve cardiac function in vivo and in vitro models of DOX-induced cardiotoxicity. This review article explores the protective effects of NCs against DOX-induced cardiac injury, with a focus on their regulation of mTOR signaling pathways. Generally, the modulation of mTOR signaling by NCs represents a promising strategy for decreasing the cardiotoxic effects of DOX., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aging is known as a main risk factor in the development of cardiovascular diseases. Naringin (NRG) is a flavonoid compound derived from citrus fruits. It possesses a wide spectrum of pharmacological properties, including antioxidant anti-inflammatory, and cardioprotective. This investigation aimed to assess the cardioprotective effect of NRG against the ischemia/reperfusion (I/R) injury in aged rats. In this study, D-galactose (D-GAL) at the dose of 150 mg/kg/day for 8 weeks was used to induce aging in rats. Rats were orally gavaged with NRG (40 or 100 mg/kg/day), in co-treatment with D-GAL, for 8 weeks. The Langendorff isolated heart was used to evaluate the effect of NRG on I/R injury in aged rats. NRG treatment diminished myocardial hypertrophy and maximum contracture level in aged animals. During the pre-ischemic phase, reduced heart rate was normalized by NRG. The effects of D-GAL on the left ventricular end diastolic pressure (LVDP), the rate pressure product (RPP), and the minimum and maximum rate of left ventricular pressure (±dp/dt) improved by NRG treatment in the perfusion period. NRG also enhanced post-ischemic recovery of cardiac functional parameters (± dp/dt, and RPP) in isolated hearts. An increase in serum levels of the lactate dehydrogenase (LDH), the creatine kinase-MB (CK-MB), and the tumor necrosis factor-alpha (TNF-α) were reversed by NRG in aged rats. It also normalized the D-GAL-decreased the superoxide dismutase (SOD) activity in the heart tissue. NRG treatment alleviated cardiac injury in aged hearts under conditions of I/R. NRG may improve aging-induced cardiac dysfunction through anti-oxidative and anti-inflammatory mechanisms., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arsenic is a toxic metalloid found in the environment in different organic and inorganic forms. Molecular mechanisms implicated in arsenic hepatotoxicity are complex but include oxidative stress, apoptosis, and autophagy. The current study focused on the potential protective capacity of melatonin against arsenic-induced hepatotoxicity. Thirty-six male Wistar rats were allocated into control, arsenic (15 mg/kg; orally), arsenic (15 mg/kg) plus melatonin (10, 20, and 30 mg/kg; intraperitoneally), and melatonin alone (30 mg/kg) groups for 28 days. After the treatment period, the serum sample was separated to measure liver enzymes (AST and ALT). The liver tissue was removed and then histological alterations, oxidative stress markers, antioxidant capacity, the levels of Nrf2 and HO-1, apoptosis (Bcl-2, survivin, Mcl1, Bax, and caspase-3), and autophagy (Sirt1, Beclin-1, and LC3 II/I ratio) proteins, as well as the expression level of miR-34a, were evaluated on this tissue. Arsenic exposure resulted in the enhancement of serum AST, ALT, and substantial histological damage in the liver. Increased levels of malondialdehyde, a lipid peroxidation marker, and decreased levels of physiological antioxidants including glutathione, superoxide dismutase, and catalase were indicators of arsenic-induced oxidative damage. The levels of Nrf2, HO-1, and antiapoptotic proteins diminished, while proapoptotic and autophagy proteins were elevated in the arsenic group concomitant with a low level of hepatic miR-34a. The co-treatment of melatonin and arsenic reversed the changes caused by arsenic. These findings showed that melatonin reduced the hepatic damage induced by arsenic due to its antioxidant and antiapoptotic properties as well as its regulatory effect on the miR-34a/Sirt1/autophagy pathway., (© 2024 Wiley Periodicals LLC.)

Chronic arsenic (As) exposure, mainly as a result of drinking contaminated water, is associated with cardiovascular diseases. Mitochondrial dysfunction, oxidative stress, inflammation, apoptosis, and autophagy have been suggested as the molecular etiology of As cardiotoxicity. Melatonin (Mel) is a powerful antioxidant. Mel improves diabetic cardiomyopathy, cardiac remodeling, and heart failure. Following pre-treatment with Mel (10, 20, or 30 mg/kg/day i.p.), rats were orally gavaged with As (15 mg/kg/day) for 28 days. Electrocardiographic findings showed that Mel decreased the As-mediated QT interval prolongation. The effects of As on cardiac levels of glutathione (GSH) and malondialdehyde (MDA) were reversed by Mel pretreatment. Mel also modulated the Sirt1 and Nrf2 expressions promoted by As. Mel down-regulated autophagy markers such as Beclin-1 expression and the LC3-II/I ratio. Moreover, the cardiac expression of cleaved-caspase-3 and Bax/Bcl-2 ratio was decreased by Mel pretreatment. Reduced expression of miR-34a and miR-144 by As were reversed by Mel. The histopathological changes of cardiac injury associated with As exposure was moderated by Mel. Mel may improve As-induced cardiac dysfunction through anti-oxidative, anti-apoptotic, and anti-autophagic mechanisms., (© 2023 International Union of Biochemistry and Molecular Biology.)

Doxorubicin (DOX) is used as a chemotherapeutic agent in the treatment of solid tumors. Irreversible cardiotoxicity is the major limitation in the clinical use of DOX. Several microRNAs (miRNAs) with diversified functions are identified that participate in exacerbating or suppressing DOX-induced cardiac damage. The miRNAs are small noncoding regulatory RNAs that modify the expression of the native genes. Studies have demonstrated that miRNAs by modifying the expression of proteins such as PTEN, Akt, and survivin can affect DOX-induced cardiac apoptosis. Moreover, miRNAs can modulate cardiac oxidative stress in DOX treatment through the posttranscriptional regulation of Sirt1, p66shc, and Nrf2 expressions. This manuscript has reviewed the regulation of the PI3K/Akt/p53 and the Sirt1/Nrf2 pathways by miRNAs in DOX-induced cardiotoxicity., (© 2022 Wiley Periodicals LLC.)

Arsenic is an abundant element in the earth's crust. In the environment and within the human body, this toxic element can be found in both organic and inorganic forms. Chronic exposure to arsenic can predispose humans to cardiovascular diseases including hypertension, stroke, atherosclerosis, and blackfoot disease. Oxidative damage induced by reactive oxygen species is a major player in arsenic-induced toxicity, and it can affect genes expression, inflammatory responses, and/or nitric oxide homeostasis. Exposure to arsenic in drinking water can lead to vascular endothelial dysfunction which is reflected by an imbalance between vascular relaxation and contraction. Arsenic has been shown to inactivate endothelial nitric oxide synthase leading to a reduction of the generation and bioavailability of nitric oxide. Ultimately, these effects increase the risk of vascular diseases such as hypertension and atherosclerosis. The present article reviews how arsenic exposure contributes to hypertension and atherosclerosis development., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The current study assessed the risk posed to Iranian consumers by oral exposure to a mixture of 20 pesticides and six metals in 96 fruit juice (FJ) samples (3 batches × 4 brands × 8 types of FJs) collected from Iran market. Concentrations of metals and pesticides in FJs were quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) and chromatography-mass spectrometry (GC-MS), respectively. The mean concentration of all pesticides was below the maximum residue limits (MRLs) set by the European Union (EU). The calculated target hazard quotients (THQs) and total hazard index (HI) were <1.0 for all pesticides residue, indicating no risk. For the carcinogenic metals (As, Ni, and Pb), estimated incremental lifetime cancer risks (ILCRs) at the 50th and 95th centiles were respectively 4.25 × 10 -5 and 5.30 × 10 -5 (for As), 2.85 × 10 -5 and 3.71 × 10 -5 (for Ni), and 2.84 × 10 -8 , and 3.97 × 10 -8 (for Pb), indicating no risk. At the 50th and 95th centiles, HI for non-carcinogenic metals (Cd, Hg, and Cr) was <1.0, indicating no risk. Based on sensitivity analyses of the input variables, the concentration of metals and pesticides, and the FJs ingestion rate had significant influential impacts on the calculated THQ and HI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Sepsis is a systemic inflammatory condition caused by an unbalanced immunological response to infection, which affects numerous organs, including the intestines. Lipopolysaccharide (LPS; also known as endotoxin), a substance found in Gram-negative bacteria, plays a major role in sepsis and is mostly responsible for the disease's morbidity and mortality. Berberine is an isoquinoline alkaloid found in a variety of plant species that has anti-inflammatory properties. For many years, berberine has been used to treat intestinal inflammation and infection. Berberine has been reported to reduce LPS-induced intestinal damage. The potential pathways through which berberine protects against LPS-induced intestinal damage by inhibiting NF-κB, suppressing MAPK, modulating ApoM/S1P pathway, inhibiting COX-2, modulating Wnt/Beta-Catenin signaling pathway, and/or increasing ZIP14 expression are reviewed. Abbreviations: LPS, lipopolysaccharide; TLR, Toll-like receptor; MD-2, myeloid differentiation factor 2; CD14, cluster of differentiation 14; LBP, lipopolysaccharide-binding protein; MYD88, myeloid differentiation primary response 88; NF-κB, nuclear factor kappa light-chain enhancer of activated B cells; MAPK, mitogen-activated protein kinase; IL, interleukin; TNFα, tumor necrosis factor-alpha; Caco-2, cyanocobalamin uptake by human colon adenocarcinoma cell line; MLCK, myosin light-chain kinase; TJ, tight junction; IκBα, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha; IBS, irritable bowel syndrome; ERK, extracellular signal-regulated kinase; JNK, c-Jun N-terminal kinase (JNK; GVB, gut-vascular barrier; ApoM, apolipoprotein M; S1P, sphingosine-1-phosphate; VE-cadherin, vascular endothelial cadherin; AJ, adherens junction; PV1, plasmalemma vesicle-associated protein-1; HDL, high-density lipoprotein; Wnt, wingless-related integration site; Fzd, 7-span transmembrane protein Frizzled; LRP, low-density lipoprotein receptor-related protein; TEER, transendothelial/transepithelial electrical resistance; COX-2, cyclooxygenase-2; iNOS, inducible nitric oxide synthase; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor-binding protein; ZIP, Zrt-Irt-like protein; PPAR, peroxisome proliferator-activated receptors; p-PPAR, phosphorylated-peroxisome proliferator-activated receptors; ATF, activating transcription factors; SOD, superoxide dismutase; GSH-Px, glutathione peroxidase; SARA, subacute ruminal acidosis; IPEC-J2, porcine intestinal epithelial cells; ALI, acute lung injury; ARDS, acute respiratory distress syndrome.

Sorting nexins (SNXs) are involved in sorting the protein cargo within the endolysosomal system. Recently, several studies have shown the role of SNXs in cardiovascular pathology. SNXs exert both physiologic and pathologic functions in the cardiovascular system by regulating protein sorting and trafficking, maintaining protein homeostasis, and participating in multiple signaling pathways. SNX deficiency results in blood pressure response to dopamine 5 receptor [D5R] stimulation. SNX knockout protected against atherosclerosis lesions by suppressing foam cell formation. Moreover, SNXs can act as endogenous anti-arrhythmic agents via maintenance of calcium homeostasis. Overexpression SNXs also can reduce cardiac fibrosis in atrial fibrillation. The SNX-STAT3 interaction in cardiac cells promoted heart failure. SNXs may have the potential to act as a pharmacological target against specific cardiovascular diseases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Various factors interfere with the endoplasmic reticulum (ER) function, which is involved in protein folding and calcium homeostasis. ER dysfunction referred to as ER stress triggers cell death by apoptosis and inflammation. Berberine (BBR) is an alkaloid extracted from the family Berberidacea. It has shown multiple pharmacological activities, including anti-inflammatory, antioxidative, anti-apoptotic, antiproliferative, and antihypertensive. It has been reported that BBR can decrease apoptosis and inflammation following different pathological conditions, which might be mediated by targeting ER stress pathways. In this manuscript, we reviewed the protective potential of BBR against several diseases, such as metabolic disorders, cancer, intestinal diseases, cardiovascular, liver, kidney, and central nervous system diseases, in both in vivo and in vitro studies., (© 2022 John Wiley & Sons Ltd.)

Vincristine, an alkaloid extracted from Catharanthus rosea, is a class of chemotherapy drugs that act by altering the function of the microtubules and by inhibiting mitosis. Despite its widespread application, a major adverse effect of vincristine that limits treatment duration is the occurrence of peripheral neuropathy (PN). PN presents with several symptoms including numbness, painful sensation, tingling, and muscle weakness. Vincristine-induced PN involves impaired calcium homeostasis, an increase of reactive oxygen species (ROS), and the upregulation of tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1β) expression. Several potential approaches to attenuate the vincristine-induced PN including the concomitant administration of chemicals with vincristine have been reported. These chemicals have a variety of pharmaceutical properties including anti-inflammation, antioxidant, and inhibition of calcium channels and calcineurin signaling pathways and increased expression of nerve growth factor (NGF). This review summarized several of these compounds and the mechanisms of action that could lead to effective options in improving vincristine-induced peripheral neuropathy (VIPN)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Metabolic syndrome is a multifactorial disorder characterized by hyperglycemia, hyperlipidemia, obesity, and hypertension risk factors. Moreover, metabolic syndrome is the most ordinary risk factor for cardiovascular disease (CVD). Numerous chemical drugs are being synthesized to heal metabolic risk factors. Still, due to their abundant side effects, herbal medicines have a vital role in the treatment of these abnormalities. Ginger ( Zingiber officinale Roscoe , Zingiberaceae) plant has been traditionally used in medicine to treat disorders, including CVD. The unique ginger properties are attributed to the presence of [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol, which through different mechanisms can be beneficial in metabolic syndrome. Ginger has a beneficial role in metabolic syndrome treatment due to its hypotensive, anti-obesity, hypoglycemic, and hypolipidemic effects. It can significantly reduce atherosclerotic lesion areas, VLDL and LDL cholesterol levels, and elevate adenosine deaminase activity in platelet and lymphocytes. Also, it promotes ATP/ADP hydrolysis. In the current article review, the critical properties of ginger and its constituents' effects on the metabolic syndrome with a special focus on different molecular and cellular mechanisms have been discussed. This article also suggests that ginger may be introduced as a therapeutic or preventive agent against metabolic syndrome after randomized clinical trials., Competing Interests: The authors declare not to have any conflicts of interest.

Cardiotoxicity can be a complication of both drugs and a variety of other chemicals that affects morbidity, quality of life, and even mortality. The accumulation of lipids and inflammation have been implicated in the development of cardiotoxicity. The peroxisome proliferator-activated receptors (PPARs), a family of transcription factors, have a role in controlling the cardiac expression of genes involved in lipid and glucose metabolism and the inflammatory response. The different PPAR isoforms, PPARα, PPARγ, and PPARβ/δ, have a role in multiple functions in cardiac tissue. The protective nature of several naturally occurring chemicals (NCs) against cardiotoxicity by targeting PPARα and PPARγ has been reported. The literature related to the ability of several NCs to modulate cardiotoxicity through targeting the AMP-activated protein kinase (AMPK)/the PPARγ coactivator-1 alpha (PGC-1α)/PPARα, the PPARα/the nuclear factor-kappa B (NF-κB), and the PPARγ/the nuclear factor-erythroid 2 related factors 2 (Nrf2)/the heme oxygenase-1 (HO-1)/NF-κB signaling pathways are reviewed., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Doxorubicin (DOX) is a potent antitumor agent with a broad spectrum of activity; however, irreversible cardiotoxicity resulting from DOX treatment is a major issue that limits its therapeutic use. Sirtuins (SIRTs) play an essential role in several physiological and pathological processes including oxidative stress, apoptosis, and inflammation. It has been reported that SIRT1 and SIRT3 can act as a protective molecular against DOX-induced myocardial injury through targeting numerous signaling pathways. Several natural compounds (NCs), such as resveratrol, sesamin, and berberine, with antioxidative, anti-inflammation, and antiapoptotic effects were evaluated for their potential to suppress the cardiotoxicity induced by DOX via targeting SIRT1 and SIRT3. Numerous NCs exerted their therapeutic effects on DOX-mediated cardiac damage via targeting different signaling pathways, including SIRT1/LKB1/AMPK, SIRT1/PGC-1α, SIRT1/NLRP3, and SIRT3/FoxO. SIRT3 also ameliorates cardiotoxicity by enhancing mitochondrial fusion., (© 2021 Wiley Periodicals LLC.)

Cardiac lipotoxicity results from the deleterious effects of excess lipid deposition in cardiomyocytes. Lipotoxic cardiomyopathy involves cardiac lipid overload leading to changes in myocardial structure and function. Cardiac dysfunction has been associated with cardiac lipotoxicity through abnormal lipid metabolism. Lipid accumulation, especially saturated free fatty acids (SFFAs), in cardiac cells can cause cardiomyocyte distress and subsequent myocardial contractile dysfunction. Reducing the excess FAs supply or promoting FA storage is beneficial for cardiac function, especially under a lipotoxic condition. The protective effects of several compounds against lipotoxicity progression in the heart have been investigated. A variety of mechanisms has been suggested to prevent or treat cardiac lipotoxicity, including improvement of calcium homeostasis, lipid metabolism, and mitochondrial dysfunction. Known targets and signaling pathways involving a select group of chemicals that interfere with cardiac lipotoxicity pathogenesis are reviewed., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Ferroptosis, an iron-dependent form of programmed cell death, is characterized by iron overload, increased reactive oxygen species (ROS) generation, and depletion of glutathione (GSH) and lipid peroxidation. Lipophilic antioxidants and iron chelators can prevent ferroptosis. GSH-dependent glutathione peroxidase 4 (GPX4) prevents lipid ROS accumulation. Ferroptosis is thought to be initiated through GPX4 inactivation. Moreover, mitochondrial iron overload derived from the degradation of ferritin is involved in increasing ROS generation. Ferroptosis has been suggested to explain the mechanism of action of organ toxicity induced by several drugs and chemicals. Inhibition of ferroptosis may provide novel therapeutic opportunities for treatment and even prevention of such organ toxicities.

Doxorubicin (DOX) is a potent chemotherapeutic agent; however, the accompanying cardiotoxicity is a significant complication of the usefulness of treatment with DOX. Multiple mechanisms have been suggested for this often fatal side effect, one of which is inflammation. Several pathways with different targets have been reported to result in DOX-induced heart inflammation. Some natural occurring compounds (NCs) have been reported to interact with the DOX-induced cardiotoxicity through targeting one or more of several pathways, including the Nrf2/NF-kB, TLR-4/NF-kB, MAPK/NF-kB, and NLRP3 inflammasome pathways. This article reviews several of these pathways and the potential protective effect of some NCs against the cardiac inflammation induced by DOX., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiac diseases are emerging due to lifestyle, urbanization, and the accelerated aging process. Oxidative stress has been associated with cardiac injury progression through interference with antioxidant strategies and endoplasmic reticulum (ER) function. Hydrogen sulfide (H 2 S) is generated endogenously from l-cysteine in various tissues including heart tissue. Pharmacological evaluation of H 2 S has suggested a potential role for H 2 S against diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, and cardiotoxicity. Nuclear factor E2-related factor 2 (Nrf2) activity is crucial for cell survival in response to oxidative stress. H 2 S up-regulates Nrf2 expression and its related signaling pathway in myocytes. H 2 S also suppresses the expression and activity of ER stress-related proteins. H 2 S has been reported to improve various cardiac conditions through antioxidant and anti-ER stress-related activities., (© 2021 International Union of Biochemistry and Molecular Biology.)

Atrial fibrillation (AF) is the most common type of cardiac rhythm disturbance. At the cellular level, excessive ROS generation during AF is associated with ER stress, which induces an inflammatory response by activating the unfolded protein response (UPR) pathway and the nuclear factor-kappa B (NF-kB) signaling pathway. Activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome has been linked to the pathogenesis of AF through NF-kB activation and inflammatory cytokine secretion. It has been shown that NLRP3 inflammasome activation by endoplasmic reticulum (ER) stress is dependent on NF-kB activation. The anti-inflammatory role of resolvin D1 (RvD1), a pro-resolving mediator derived from omega-3 fatty acids, has demonstrated that the NF-κB/NLRP3 inflammasome pathway in different tissues is attenuated after treatment with RvD1. However, the mechanism of the anti-inflammatory activity of RvD1 in AF has not been clarified. This review suggests that RvD1 may inhibit ER stress-induced NLRP3 inflammasome through suppressing NF-κB in cardiac tissue and, thus ameliorate AF., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Cardiotoxicity is a major adverse effect that can be induced by both therapeutic agents and industrial chemicals. The pathogenesis of such cardiac damage is multifactorial, often injuring the cardiac tissue by generating free radicals, oxidative stress, and/or inflammation. Curcumin (CUR) is a bright yellow chemical produced by Curcuma longa plants. It is the principal curcuminoid of turmeric (Curcuma longa), a member of the ginger family, Zingiberaceae. Administration of CUR has been reported to ameliorate the chemical and drug-induced cardiac injury in several studies. CUR has been suggested to act as an effective candidate against oxidative stress and inflammation in heart tissue via regulation of Nrf2 and suppression of p38 MAPK/NF-κB and NLRP3 inflammasomes. The anti-apoptotic properties of CUR have also been reported to modulate the AMPK, Akt, JNK, and ERK signaling pathways. This review explores the potential protective effects of CUR regarding the detrimental effects often observed in cardiac tissue following exposure to several chemicals including drugs.

Metabolic syndrome (MetS), also known as syndrome X, is a significant risk factor for cardiovascular disease incidence and mortality. Increasing age, obesity, physical inactivity, smoking, and positive family history are the risk factors associated with MetS, which increases the risk of diabetes, cardiovascular disease, hypertension, hyperlipidemia, and obesity. Chemical compounds in the treatment of metabolic complications are associated with a lack of efficacy and severe side effects. Numerous studies have described the importance of herbs and natural products to treat human diseases. Therefore, nowadays, herbs-based diets and herbal medicines are recommended for the management of various diseases. The protective effects of several herbs have been reported against MetS such as rosemary, avocado, and silymarin. Eggplant ( Solanum melongena ) is a rich source of phenolic and alkaloid compounds. It possesses various pharmacological effects, including, anti-oxidant, antidiabetic, antihypertensive, and antihyperlipidemic, which has been supported by numerous investigations. In this review, we evaluated the effects of eggplant on MetS and its complications comprising diabetes, high blood pressure, hyperlipidemia, and obesity. According to these studies, eggplant can control diabetes through the anti-oxidative properties and inhibition of α-amylase and α-glucosidase activity. Also, eggplant has exerted an antihypertensive effect via ACE inhibitory activity. Eggplant may have shown protective effects on hyperlipidemia and obesity via the induction of lipoprotein lipase activity and the reduction of pancreatic lipase activity.Eggplant can be useful in the treatment of MetS and its complications.

Metabolic syndrome is a condition associated with obesity, diabetes, dyslipidemia, and high blood pressure. Recently, the use of phytochemicals is suggested in the control and treatment of metabolic syndrome. The Azadirachta indica (neem) is an evergreen tree belonging to the family of Meliaceae. Multiple studies have been confirmed the anti-diabetic and anti-hypertension, anti-hyperlipidemia, and anti-obesity effects of neem. In this review, we reported the protective effects of neem against the complications of metabolic syndrome with a special focus on mechanisms that are involved. It has been shown that neem can control hyperglycemia and hypertension through over-expression of transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and anti-oxidant effects. Neem also reduced the glucose uptake through up-regulation of glucose transporter 4 (GLUT4) and inhibition of key intestinal enzymes such as glucosidases. Moreover, neem showed anti-hypertensive effects possibility via the block of calcium channels, up-regulation of endothelial nitric oxide synthase (eNOS), and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway. Anti-oxidant effects play an important role in protective mechanisms of neem against metabolic syndrome and its complications.

Cardiotoxicity is the main concern for long-term use of the doxorubicin (DOX). Reactive oxygen species (ROS) generation leads to oxidative stress that significantly contributes to the cardiac damage induced by DOX. The nuclear factor erythroid 2-related factor (Nrf2) acts as a protective player against DOX-induced myocardial oxidative stress. Several natural compounds (NCs) with anti-oxidative effects, were examined to suppress DOX cardiotoxicity such as asiatic acid, α-linolenic acid, apigenin, baicalein, β-lapachone, curdione, dioscin, ferulic acid, Ganoderma lucidum polysaccharides, genistein, ginsenoside Rg3, indole-3-carbinol, naringenin-7-O-glucoside, neferine, p-coumaric acid, pristimerin, punicalagin, quercetin, sulforaphane, and tanshinone IIA. The present article, reviews NCs that showed protective effects against DOX-induced cardiac injury through induction of Nrf2 signaling pathway., (© 2020 John Wiley & Sons Ltd.)

Cardiotoxicity is a critical concern in the use of several cytotoxic drugs. Induction of apoptosis, inflammation, and autophagy following dysregulation of the PI3K/Akt signaling pathway contributes to the cardiac damage induced by these drugs. Several natural compounds (NCs), including ferulic acid, gingerol, salvianolic acid B, paeonol, apigenin, calycosin, rutin, neferine, higenamine, vincristine, micheliolide, astragaloside IV, and astragalus polysaccharide, have been reported to suppress cytotoxic drug-induced cardiac injury. This article reviews these NCs that have been reported to have a protective effect against cytotoxic drug-induced cardiotoxicity through regulation of the PI3K/Akt signaling pathway., (© 2020 Wiley Periodicals LLC.)

Doxorubicin (DOX) is a chemotherapeutic agent with marked, dose-dependent cardiotoxicity that leads to tachycardia, atrial and ventricular arrhythmia, and irreversible heart failure. Induction of the endoplasmic reticulum (ER) which plays a major role in protein folding and calcium homeostasis was reported as a key contributor to cardiac complications of DOX. This article reviews several chemical compounds that have been shown to regulate DOX-induced inflammation, apoptosis, and autophagy via inhibition of ER stress signaling pathways, such as the IRE1α/ASK1/JNK, IRE1α/JNK/Beclin-1, and CHOP pathways., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Rotenone is a widely used organic pesticide; its serious side effect for off-target species is neurotoxicity. The primary mechanism of rotenone toxicity is inhibition of the mitochondrial complex I. Oxidative stress, apoptosis, and reduction of autophagy are key outcomes of the inhibition of complex I. Numerous in vitro and in vivo studies have shown antioxidant, anti-apoptotic, and autophagy enhancement of a variety of natural compounds (NCs). In this manuscript, we reviewed several NCs, which have protective effects against rotenone-induced neurotoxicity., (© 2020 Wiley Periodicals LLC.)

The neuro-protective effects of rubidium and lithium as alkali metals have been reported for different central nervous system dysfunctions including mania and depression. The aim of this study was evaluating as well as comparing the effects of rubidium chloride (RbCl) and lithium chloride (LiCl) on different seizures paradigms in mice and determining the involvement of NMDA receptors and nitrergic pathway. To assess the seizures threshold, animals received intravenous pentylenetetrazole (PTZ, 0.5%; 1 mL/min). Male NMRI mice (6-8 weeks) received intraperitoneal (i.p.) injections of different doses of RbCl and LiCl. Doses greater than 10 mg/kg of RbCl showed a significant anticonvulsant activity 60 min after administration; the anticonvulsant effects of LiCl was observed at the doses more than 5 mg/kg and after 30 min in PTZ-induced seizure threshold. But, RbCl (10, 20 mg/kg, i.p) or LiCl (5, 10 mg/kg, i.p) injection did not induce protection against maximal electroshock (MES) or intraperitoneal injection of PTZ lethal dose (80 mg/kg)-induced seizure models. Pre-treatment with L-NAME (non-selective nitric oxide synthase (NOS) inhibitor, 10 mg/kg; i.p.) and 7-nitroindazole (selective neuronal NOS inhibitor, 30 mg/kg; i.p.) enhanced the anticonvulsive effects of both RbCl (5 mg/kg, i.p.) and LiCl (1 mg/kg, i.p.) in PTZ-induced seizure threshold model. Injection of MK-801 (NMDA receptor antagonist, 0.05 mg/kg; i.p.) before RbCl (5 mg/kg, i.p.; P < 0.001) and LiCl (1 mg/kg, i.p.; P < 0.001) administration increased the anti-seizure activity. But, treatment with L-arginine (precursor of nitric oxide, 100 mg/kg; i.p.) decreased the seizure threshold of both RbCl (20 mg/kg, i.p.; P < 0.001) and LiCl (10 mg/kg, i.p.; P < 0.001). Measurement of nitrite levels in hippocampus of animals revealed a remarkable reduction after treatment with RbCl (20 mg/kg, i.p; P < 0.05) and LiCl (10 mg/kg, i.p; P < 0.01). To conclude, rubidium may protect central nervous system against seizures in PTZ-induced seizures threshold model through NMDA/nitrergic pathways with a similarity to lithium effects in mice., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: Alpha7 nicotinic acetylcholine receptor (α7-nAChR), an emerging pharmacological target for a variety of medical conditions, is expressed in the most mammalian tissues with different effects. So, this study was designed to investigate the expression, localization and effect of α7-nAChR in rat corpus cavernosum (CC)., Methods & Key Findings: Reverse transcription polymerase chain reaction (RT-PCR) revealed that α7-nAChR was expressed in rat CC and double immunofluorescence studies demonstrated the presence of α7-nAChR in corporal neurons. The rat CC segments were mounted in organ bath chambers and contracted with phenylephrine (0.1 μm -300 μm) to investigate the relaxation effect of electrical field stimulation (EFS,10 Hz) assessed in the presence of guanethidine (adrenergic blocker, 5 μm) and atropine (muscarinic cholinergic blocker, 1 μm) to obtain non-adrenergic non-cholinergic (NANC) response. Cumulative administration of nicotine significantly potentiated the EFS-induced NANC relaxation (-log EC50 = 7.5 ± 0.057). Whereas, the potentiated NANC relaxation of nicotine was significantly inhibited with different concentrations of methyllycaconitine citrate (α7-nAChR antagonist, P < 0.05) in preincubated strips. L-NAME (non-specific nitric oxide synthase inhibitor, 1 μm) completely blocked the neurogenic relaxation induced by EFS plus nicotine., Conclusion: To conclude α7-nAChR is expressed in rat CC and modulates the neurogenic relaxation response to nicotine., (© 2017 Royal Pharmaceutical Society.)