Hesperidin neuroprotective effects against carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats.

Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Occupational respiratory disorders in Iran: a review of prevalence and inducers.

The link between occupational respiratory diseases (ORD) and exposure to harmful factors that are present in the workplace has been well shown. Factors such as physical activity, age and duration of occupational exposure playing important roles in ORD severity, should be identified in the workplace, their effects on workers health should be studied, and ultimately, exposure to them must be minimized. We carried out a literature review by searching PubMed, Scopus, and Web of Science databases to retrieve studies published from 1999 until the end of April 2023 reporting the prevalence and inducers of ORD in Iran. In Iranian workers, several ORD such as interstitial lung disease, silicosis, occupational asthma, pulmonary inflammatory diseases, chronic obstructive pulmonary diseases, and lung cancers have been reported. It was indicated that ORD mainly occur due to repeated and prolonged exposure to noxious agents in the workplace. We also extracted the prevalence of ORD in different regions of Iran from the retrieved reports. Based on our literature review, the prevalence of ORD among Iranian workers highlights the importance of regular assessment of the risk of exposure to noxious agents in the workplace to develop measures for preventing potential adverse effects.

Hormetic effects of curcumin on oxidative stress injury induced by trivalent arsenic in isolated rat hepatocytes.

Objective: Arsenic (As) poisoning is a worldwide public health problem. Arsenic can cause cancer, diabetes, hepatic problems, etc. Hence, we investigated possible hepatoprotective properties of curcumin against As3+-induced liver damages in freshly isolated rat hepatocytes. Materials and Methods: Isolation of hepatocytes was done by the two-step liver perfusion method using collagenase. The EC50 concentration of As3+ was used in toxicity assessments and curcumin (2, 5, and 10 µM) was added 15 min before As3+ addition to isolated hepatocytes. Curcumin impact was assessed in terms of cytotoxicity, lipid peroxidation induction, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Results: As3+ significantly increased cytotoxicity, malondialdehyde and ROS levels and induced mitochondrial membrane damage and hepatocyte membrane lysis after 3 hr incubation. Curcumin 2 µM significantly prevented lipid peroxidation induction, ROS formation, and mitochondrial membrane damage; while curcumin 5 µM had no apparent effect on these parameters, curcumin 10 µM potentiated them. Conclusion: Curcumin only at low doses could ameliorate oxidative stress injury induced by As3+ in isolated rat hepatocytes.

Pharmacological effects of Safranal: An updated review.

Safranal (a monoterpene aldehyde) is the major volatile component of saffron which is responsible for the saffron unique odor. Several studies have shown the pharmacological activities of safranal including anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, nephroprotective, gastrointestinal protective, etc. This study was designed to review the pharmacological and medical effects of safranal and up-to-date previous knowledge. Moreover, some patents related to the pharmacological effects of safranal were gathered. Therefore, electronic databases including Web of Sciences, Scopus, and Pubmed for pharmacological effects and US patent, Patentscope, and Google Patent for patents were comprehensively searched by related English keywords from 2010 to June 2022. According to our review, most of the studies are related to the safranal effects on CNS such as antianxiety, analgesic, anticonvulsant, antiischemic, anti-tremor, memory enhancement and its protective effects on neurodegenerative disorders such as Alzheimer's, Parkinson and Huntington diseases. Other effects of safranal are antiasthmatic, antihypertensive, antiaging, anticataract, etc. Moreover, the protective effects of this agent on metabolic syndrome and diabetic nephropathy have been shown. Different mechanisms including anti-oxidant, anti-inflammatory, muscle relaxation, antiapoptotic, and regulatory effects on the genes and proteins expression related to signaling pathways of oxidative stress, inflammation, apoptosis, proliferation, etc. are involved in safranal pharmacological effects. Some patents for the prevention and/or treatment of different diseases such as liver cancer, sleep disorder, depression, cognitive disorder, obesity and PMS were also included. Based on the documents, safranal is considered a promising therapeutic agent although more clinical studies are needed to verify the beneficial effects of safranal in humans.

Reproductive Toxicity of Nanoparticles: A Comprehensive Review.

The unique characteristics of nanoparticles (NPs) have captivated scientists in various fields of research. However, their safety profile has not been fully scrutinized. In this regard, the effects of NPs on the reproductive system of animals and humankind have been a matter of concern. In this article, we will review the potential reproductive toxicity of various types of NPs, including carbon nanomaterials, dendrimers, quantum dots, silica, gold, and magnetic nanoparticles, reported in the literature. We also mention some notable cases where NPs have elicited beneficial effects on the reproductive system. This review provides extensive insight into the effects of various NPs on sperm and ovum and the outcomes of their passage through blood-testis and placental barriers and accumulation in the reproductive organs.

Probabilistic risk assessment of exposure to multiple mycotoxins in consumers of packaged and unpackaged spices in Iran.

The current study assessed the risk posed to Iranian consumers by oral exposure to a mixture of ten mycotoxins in 138 packaged and unpackaged spices collected from the Iran market. Concentrations of mycotoxins in samples were quantified by liquid chromatography, tandem mass spectrometry with triple quadrupole, and ion trap. Probabilistic health risks of oral exposure to these mycotoxins for Iranians were assessed under percent tolerable daily intake (TDI) and cancer risk scenarios. Mean concentrations of mycotoxins in both packaged and unpackaged spice samples showed statistically significant variation among different spice samples. Based on a Monte Carlo simulation model, at the 50th, 80th, and 95th centiles, oral consumption of the analyzed samples poses no carcinogenic risk for exposure to aflatoxin. Moreover, in both packaged and unpackaged samples, while the percent TDIs for ochratoxin A, deoxynivalenol, zearalenone, patulin, fumonisin B1, and fumonisin B2 were below 1.0 at the 50th, 80th, and 95th centiles, the value was above 1.0 for aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 at each of these centiles.

A New Nonlinear Autoregressive Exogenous (NARX)-based Intra-spinal Stimulation Approach to Decode Brain Electrical Activity for Restoration of Leg Movement in Spinally-injured Rabbits.

Introduction: This study aimed at investigating the stimulation by intra-spinal signals decoded from electrocorticography (ECoG) assessments to restore the movements of the leg in an animal model of spinal cord injury (SCI). Methods: The present work is comprised of three steps. First, ECoG signals and the associated leg joint changes (hip, knee, and ankle) in sedated healthy rabbits were recorded in different trials. Second, an appropriate set of intra-spinal electric stimuli was discovered to restore natural leg movements, using the three leg joint movements under a fuzzy-controlled strategy in spinally-injured rabbits under anesthesia. Third, a nonlinear autoregressive exogenous (NARX) neural network model was developed to produce appropriate intra-spinal stimulation developed from decoded ECoG information. The model was able to correlate the ECoG signal data to the intra-spinal stimulation data and finally, induced desired leg movements. In this study, leg movements were also developed from offline ECoG signals (deciphered from rabbits that were not injured) as well as online ECoG data (extracted from the same rabbit after SCI induction). Results: Based on our data, the correlation coefficient was 0.74±0.15 and the normalized root means square error of the brain-spine interface was 0.22±0.10. Conclusion: Overall, we found that using NARX, appropriate information from ECoG recordings can be extracted and used for the generation of proper intra-spinal electric stimulations for restoration of natural leg movements lost due to SCI.

Exposure to anesthetic gases in the operating rooms and assessment of non-carcinogenic risk among health care workers.

Health care workers employed operating room in hospital and health centers are unavoidably exposed to inhaling toxic gases, including isoflurane and sevoflurane. Chronic contact with these gases increases the risk of spontaneous abortion, congenital anomalies and cancers. Risk assessment is an important tool in predicting the possible risk to personnel's health. Therefore, this study was conducted with the aim of determining the concentration of isoflurane and sevoflurane gas in the air of the operating room and estimating the non-carcinogenic risk caused by them. In this descriptive-cross-sectional study, according to the occupational method (OSHA 103), 23 samples (isoflurane and sevoflurane) were collected in the air of operating rooms of four selected hospitals in Ahvaz city by using SKC sampling pumps and sorbent tube (Anasorb 747). The samples were determined by used to gas chromatography with a flame ionization detector (GC/FID). Statistical analysis, including the Kruskal-Wallis test, was used to compare the average concentration of anesthetic gases, and the one-sample t-test was used to compare the average with the standard level. In all analyses, the significance level was 0.05, which was performed by SPSS version 22 software. Result of this study showed that the average concentration of isoflurane in private and general hospitals were 23.636 and 17.575 ppm, respectively. Also, the average level of sevoflurane were 1.58 and 7.804 ppm. According to the results the mean amount of anesthetic gases was within the range recommended by Iran's Occupational and Environmental Health Center and the permissible threshold limit provided by ACGIH. In addition, non-cancer risks from occupational exposure to isoflurane and sevoflurane in selected private and general hospitals were acceptable (HQ < 1). Although the results show that overall occupational exposure to anesthetic gases is less than acceptable but long-term exposure to anesthetic gases may endanger the health of operating room staffs. Therefore, it is recommended to implement some technical controls, including regular inspection of ventilation systems, the use of advanced ventilation systems with high cleaning power, continuous control of anesthesia devices in terms of leakage, and periodic training of related staff.

Oral Nicorandil effectively attenuates the incidence of contrast-induced nephropathy in patients undergoing cardiac catheterization: a randomized, controlled, open-label clinical trial.

PURPOSE: The contrast-induced nephropathy (CIN) rate is increasing globally and can increase the rate of mortality and long-term problems. This study aims to determine the effect of Nicorandil on preventing CIN among patients undergoing cardiac catheterization. METHODS: In a controlled randomized open-labeled clinical trial, all included patients undergoing cardiac catheterization due to coronary problems and possessing at least two risk factors of contrast nephropathy were divided into two groups of intervention and control. The intervention group received oral Nicorandil and normal saline, while the control group was treated with intravenous normal saline. Serum creatinine was measured before and 48 h after the procedure, and patients were assessed regarding CIN. RESULTS: In this study, 172 patients entered each group; 41.86% and 45.34% were male in the control and Nicorandil groups. We showed that the incidence of CIN was meaningfully lower in the Nicorandil group (12, 7%) than in the control group (34, 19.8%, P = 0.001). Additionally, the incidence of CIN was notably lower in the female patients in the Nicorandil (85.7%) than in the control group (14.3%, P = 0.001); however, these numbers were not significantly different among men (64.0% and 36.0%, respectively, P = 0.850). After the injection of the contrast agent, the serum levels of blood urea nitrogen (P = 0.248), creatinine (P = 0.081), and glomerular filtration rate (P = 0.386) showed no significant differences between the control and Nicorandil groups. Multivariate regression analysis showed that Nicorandil significantly lowered the odds of CIN [odds ratio (OR) = 0.299, 95% confidence interval (CI) 0.149-0.602; P = 0.001] after adjustment for baseline creatinine (OR = 1.404, 95% CI 0.431-4.572; P = 0.574). CONCLUSION: Our results indicate that pre-procedural treatment with Nicorandil may be effective against CIN in contrast to agent-exposed patients.

Natural compounds regulate the PI3K/Akt/GSK3ß pathway in myocardial ischemia-reperfusion injury.

The PI3K/Akt/GSK3ß pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3ß) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3ß regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3ß pathway in cardioprotective effects of natural products against MIRI.Abbreviations: Akt: protein kinase B; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; Bad: bcl2-associated agonist of cell death; Bax: bcl2-associated x protein; Bcl-2: B-cell lymphoma 2; CK-MB: Creatine kinase-MB; CRP: C-reactive-protein; cTnI: cardiac troponin I; EGCG: Epigallocatechin-3-gallate; Enos: endothelial nitric oxide synthase; ER: endoplasmic reticulum; ERK ½: extracellular signal­regulated protein kinase ½; GSK3ß: glycogen synthase kinase-3; GSRd: Ginsenoside Rd; GSH: glutathione; GSSG: glutathione disulfide; HO-1: heme oxygenase-1; HR: hypoxia/reoxygenation; HSYA: Hydroxysafflor Yellow A; ICAM-1: Intercellular Adhesion Molecule 1; IKK-b: IκB kinase; IL: interleukin; IPoC: Ischemic postconditioning; IRI: ischemia-reperfusion injury; JNK: c-Jun N-terminal kinase; Keap1: kelch-like ECH-associated protein- 1; LDH: lactate dehydrogenase; LVEDP: left ventricular end diastolic pressure; LVP: left ventricle pressure; LVSP: left ventricular systolic pressure; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde; MIRI: myocardial ischemia-reperfusion injury; MnSOD: manganese superoxide dismutase; mPTP: mitochondrial permeability transition pore; mtHKII: mitochondria-bound hexokinase II; Nrf-1: nuclear respiratory factor 1; Nrf2: nuclear factor erythroid 2-related factor; NO: nitric oxide; PGC-1α: peroxisome proliferator­activated receptor γ coactivator­1α; PI3K: phosphoinositide 3-kinases; RISK: reperfusion injury salvage kinase; ROS: reactive oxygen species; RSV: Resveratrol; SOD: superoxide dismutase; TFAM: transcription factor A mitochondrial; TNF-α: tumor necrosis factor-alpha; VEGF-B: vascular endothelial growth factor B.

Mechanisms of Arsenic Exposure-Induced Hypertension and Atherosclerosis: an Updated Overview.

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.

Assessment of Carcinogenic and Non-carcinogenic Risk of Exposure to Metals via Consumption of Coffee, Tea, and Herbal Tea in Iranians.

In the current study, we assessed health risk posed to Iranian consumers through exposure to metals via oral consumption of coffee, tea, and herbal tea of various trademarks collected from Iran market. Level of As, Cd, Cr, Cu, Fe, Hg, Ni, and Pb in 243 samples was quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES). The metal levels in coffee samples from different trademarks of a specific country had statistically similar levels of metals; however, metal levels differed significantly among brand names form different countries. Metal levels in tea samples differed significantly between domestic and imported products, while different trademarks of similar countries did not show significant variations in this respect. Metal level in herbal tea samples did not show significant variations among different trademarks. Nevertheless, it should be highlighted that mean concentrations of metals statistically differed among different herbal tea samples. Deterministic hazard quotients (HQs) were <1.0 for all non-carcinogenic metals and total hazard index (HI) values indicated no risk; however, probabilistic assessment calculated HI values >1. In both deterministic and probabilistic scenarios, carcinogenic metals As and Ni had an estimated incremental lifetime cancer risk (ILCR) of medium level while that of Pb indicated no cancer risk. Sensitivity analysis showed that the concentration of metals had the most significant effect on non-carcinogenic and carcinogenic risks.

A review of mechanisms underlying the protective effects of natural compounds against arsenic-induced neurotoxicity.

Arsenic (As) is a toxic metalloid that is widely distributed in the earth's crust. People are continuously exposed to this toxicant in their food and drinking water. Inorganic arsenic occurs in two oxidation states, arsenite 3+ (iAs3+) and arsenate 5+ (iAs5+). The most toxic form is its trivalent form which interferes with the electron transfer cycle and induces overproduction of reactive oxygen species, leading to depletion of the antioxidant defense system, as well as altering fatty acid levels and mitochondrial action. Since arsenic crosses the blood-brain barrier, it can damage cells in different regions of the brain, causing neurological disorders through the induction of oxidative stress, inflammation, DNA damage, and cell death. Hydroxytyrosol, taurine, alpha-lipoic acid, ellagic acid, and thymoquinone have been shown to effectively alleviate arsenic-induced neurotoxicity. The protective effects are the result of the anti-oxidative and anti-inflammatory properties of the phytochemicals and in particular their anti-apoptotic function via the Nrf2 and PI3/Akt/SIRT1 signaling pathways.

Probabilistic risk assessment of exposure to multiple metals and pesticides through consumption of fruit juice samples collected from Iranian market.

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.

Induction of JAK2/STAT3 pathway contributes to protective effects of different therapeutics against myocardial ischemia/reperfusion.

Insufficiency in coronary blood supply results in myocardial ischemia and consequently, various clinical syndromes and irreversible injuries. Myocardial damage occurs as a result of two processes during acute myocardial infarction (MI): ischemia and subsequent reperfusion. According to the available evidence, oxidative stress, excessive inflammation reaction, reactive oxygen species (ROS) generation, and apoptosis are crucial players in the pathogenesis of myocardial ischemia/reperfusion (IR) injury. There is emerging evidence that Janus tyrosine kinase 2 (JAK2) signal transducer and activator of the transcription 3 (STAT3) pathway offers cardioprotection against myocardial IR injury. This article reviews therapeutics that exert cardioprotective effects against myocardial IR injury through induction of JAK2/STAT3 pathway.

Effects of gallic acid on intraperitoneal adhesion bands in rats.

Objective: Gallic acid (GA) is an organic acid that possesses anti-inflammatory effects as it inhibits the production of metalloproteinases, tissue plasminogen activator, growth factors and adhesion molecules. Since formation of abdominal surgery-induced adhesion bands is accompanied by inflammation, angiogenesis and cell proliferation, in the current study, we assessed potential beneficial properties of GA against adhesion bands formation in rats. Materials and Methods: Thirty-six adult male rats were assigned into six groups of six animals. After induction of anesthesia, peritoneal injury was induced using a standard method and animals received either GA (10, 25, 50 and 100 mg/kg), or normal saline, while a group of rats remained intact. Seven days after the surgery, animals were decapitated and samples were collected for pathology evaluations. Also, lipid peroxidation (TBARS) and tumor necrosis factor alpha (TNF-α) levels were determined in serum samples. Results: Our results showed that GA significantly reduced lipid peroxidation in serum samples but had no effect on TNF-α levels. Furthermore, microscopic and macroscopic injuries reduced significantly in GA-treated animals. Conclusion: Since GA reduced adhesion bands formation at microscopic and macroscopic levels, it could be considered a treatment against adhesion bands formation.