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.

Endoplasmic reticulum stress in doxorubicin-induced cardiotoxicity may be therapeutically targeted by natural and chemical compounds: A review.

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.

Increased age, neutrophil-to-lymphocyte ratio (NLR) and white blood cells count are associated with higher COVID-19 mortality.

OBJECTIVE: Coronavirus disease 19 (COVID-19) caused by the highly pathogenic SARS-CoV-2, was first reported from Wuhan, China, in December 2019. The present study assessed possible associations between one-month mortality and demographic data, SpO2, underlying diseases and laboratory findings, in COVID-19 patients. Also, since recent studies on COVID-19, have focused on Neutrophil-to-lymphocyte ratio (NLR) as an independent risk factor of the in-hospital death and a significant prognostic biomarker of outcomes in critically ill patients, in this study, we assessed predictive potential of this factor in terms of one-month mortality. METHODS: Patients admitted to Imam Reza hospital, affiliated to Mashhad University of Medical Sciences, Mashhad, Iran, from March to June 2020, with positive RT-PCR results for SARS-CoV-2, were included in this study. Kaplan-Meier survival analysis and Cox proportional hazard model were used to respectively estimate one-month mortality since admission and determine factors associated with one-month mortality. RESULTS: In this retrospective cohort study, 219 patients were included (137 men and 82 women (mean age 58.2 ± 16 and 57 ± 17.3 years old, respectively)). Hypertension, ischemic heart disease and diabetes were respectively the most common comorbidities. Among these patients, 63 patients were admitted to the ICU and 31 deaths occurred during one-month follow-up. With respect to mean peripheral capillary oxygen saturation (SpO2), 142 patients had SpO2 ≤ 90%. Based on our analysis, older age and increased Neutrophil-to-lymphocyte ratio (NLR), and White blood cells (WBC) count were associated with increased risk of one-month mortality. Patients with SpO2 ≤ 90% had a 3.8-fold increase in risk of one-month death compared to those with SpO2 > 90%, although the difference did not reach a significant level. CONCLUSION: Multivariate analysis introduced age, WBC count, and NLR as predictors of one-month mortality in COVID-19 patients.

A review on pain-relieving activity of berberine.

As isoquinoline alkaloid naturally occurs in Coptis and Berberis species, berberine (BER) has shown anti-oxidant, anti-tumour, anti-bacterial and hepatoprotective activities and beneficial effects against digestive, cardiovascular and neurological conditions. Also, BER antiinflammatory, pain-relieving and anti-cholinesterase activities were widely studied. The present overview discusses the analgesic effects of BER. Based on the literature, BER exerted pain-relieving activity against diabetic and chemotherapy-induced neuropathy, and sciatic nerve injury-induced pain via down-regulation of transient receptor potential vanilloid 1, suppression of NF-κB and modulation of µ and δ opioid receptors. Besides, BER could repress inflammatory markers tumour necrosis factor-α, interleukin-6 and IL-1ß, as well as prostaglandin E2, inducible nitric oxide synthase and cyclooxygenase-2. The modulatory effects of BER on dopamine and N-methyl d-aspartate systems were also noted. Moreover, BER could induce Nrf2 expression but inhibits p38-MAPK and STAT3 phosphorylation. Noteworthy, anti-cholinesterase activity, which may potentially contribute to BER analgesic properties, warrants particular attention.

A review on the protective effects of naringenin against natural and chemical toxic agents.

Naringenin (NRG), as a flavanone from flavonoids family, is widely found in grapefruit, lemon tomato, and Citrus fruits. NRG has shown strong anti-inflammatory and antioxidant activities in body organs via mechanisms such as enhancement of glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity, but reduction of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Furthermore, NRG anti-apoptotic potential was indicated to be mediated by regulating B-cell lymphoma (Bcl-2), Bcl-2-associated X protein (Bax) and caspase3/9. Overall, these properties make NRG a highly fascinating compound with beneficial pharmacological effects. Based on the literature, NRG-induced protective effects against toxicities produced by natural toxins, pharmaceuticals, heavy metals, and environmental chemicals, were mainly mediated via suppression of lipid peroxidation, oxidative stress (through boosting the antioxidant arsenal), and inflammatory factors (e.g., TNF-α, interleukin [IL]-6, IL-10, and IL-12), and activation of PI3K/Akt and MAPK survival signaling pathways. Despite considerable body of evidence on protective properties of NRG against a variety of toxic compounds, more well-designed experimental studies and particularly, clinical trials are required before reaching a concrete conclusion. The present review discusses how NRG protects against the above-noted toxic compounds.

Natural compounds against doxorubicin-induced cardiotoxicity: A review on the involvement of Nrf2/ARE signaling pathway.

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, ß-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.

Mangiferin offers protection against deleterious effects of pharmaceuticals, heavy metals, and environmental chemicals.

Mangiferin (MGF) is a polyphenolic C-glucosyl-xanthone extracted from the mango tree (Mangifera indica). MGF has shown diverse effects such as antioxidant, antiapoptotic, radical scavenging, and chelating properties. MGF also has been shown to modulate inflammatory pathways. In this review, we examined and evaluated the literature dealing with the protective effects of MGF against various chemical toxicities. Our literature review indicated that the MGF-induced protective effects against the toxic effects of pharmaceuticals, heavy metals and environmental chemicals were mainly mediated via suppression of lipid peroxidation, oxidative stress (along with enhancement of the antioxidant enzyme), inflammatory factors (TNF-α, IL-6, IL-10, and IL-12), and activation of PI3K/Akt and the MAPK survival signaling pathway.

Cardioprotective effects of hesperidin on carbon monoxide poisoned in rats.

Carbon monoxide (CO) poisoning causes cardiotoxicity and so far, no definite antidote has been proposed to overcome CO-induced adverse outcomes. Hesperidin, a citrus flavonoid, has shown cardio-protective effects in cardiac ischemia/reperfusion models. This study investigated the protective effects of hesperidin against CO-induced cardiac injury. To induce CO poisoning, rats were exposed to CO at 3000 ppm for 60 min. On the exposure day and the four following days, hesperidin (at three different doses of 25, 50, and 100 mg/kg/day) was administered intraperitoneally. A group of animals received normal saline and served as the control group. The electrocardiogram (ECG) was recorded and evaluated with special focus on S-T segment changes (depression or elevation), T-wave alterations, AV block and ventricular and supraventricular arrhythmias. On day 6 (i.e., the day after the last injection day), the animals were sacrificed and the hearts were harvested and evaluated for necrosis using hematoxylin and eosin staining. In addition, Akt protein expression levels and BAX/BCL2 ratio were determined by western blotting. Our results showed that hesperidin decreased cardiac necrosis. In animals treated with hesperidin 100 mg/kg, Akt protein expression was increased, while the BAX/BCL2 ratio was significantly decreased. ECG changes were reversed in all groups 2 h following CO exposure, regardless of hesperidin administration. Overall, hesperidin decreased the deleterious cardiac effects of CO poisoning in rats.

Knowledge, attitude, and practice of pharmacy and medical students regarding self-medication, a study in Zabol University of Medical Sciences; Sistan and Baluchestan province in south-east of Iran.

BACKGROUND: Self-medication is defined as using medicinal products to treat the disorders or symptoms diagnosed by oneself. Although informed self-medication is one of the ways to reduce health care costs, inappropriate self-treatment can pose various risks including drug side effects, recurrence of symptoms, drug resistance, etc. The purpose of this study was to investigate the knowledge, attitude, and practice of pharmacy and medical students toward self-medication. METHODS: This study was conducted in Zabol University of Medical Sciences in 2018. Overall, 170 pharmacy and medical students were included. A three-part researcher-made questionnaire was designed to address the students' knowledge, attitude, and practice. Statistical analysis was performed in SPSS 25 software. RESULTS: According to the results, 97 (57.1%) students had carried out self-medication within the past 6 months. Overall, the students self-medicated on average 4.2 ± 2.9 times per year. Self-medication was more common in male students (65.4%, P = 0.043). Cold was the most common ailment treated with self-medication (93.2%), and antibiotics (74.4%) were the most commonly used drugs. The primary information sources used by the students were their previous prescriptions (47.4%). Pharmacy students had a higher level of drug information (P < 0.001). There was a statistically significant association between the level of drug information and the tendency for self-medication (P = 0.005). Disease recurrence was the most common negative complication of self-medication. CONCLUSION: There is a need to educate pharmacy and medical students regarding self-medication and its side effects. The high prevalence of self-medication and the overuse of antibiotics can pose a significant risk of drug resistance.

A review of anti-inflammatory, antioxidant, and immunomodulatory effects of Allium cepa and its main constituents.

CONTEXT: Allium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects. OBJECTIVE: Anti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented. METHODS: Databases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory. RESULTS: A. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1ß and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance). CONCLUSIONS: The effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.

Molecular Mechanisms Mediating Adaptation to Exercise.

Several experimental and human studies documented the preventive and therapeutic effects of exercise on the normal physiological function of different body systems during aging as well as various diseases. Recent studies using cellular and molecular (biochemical, proteomics, and genomics) techniques indicated that exercise modifies intracellular and extracellular signaling and pathways. In addition, in vivo or in vitro experiments, particularly, using knockout and transgenic animals, helped to mimic physiological conditions during and after exercise. According to the findings of these studies, some important signaling pathways modulated by exercise are Ca2+-dependent calcineurin/activated nuclear factor of activated T-cells, mammalian target of rapamycin, myostatin/Smad, and AMP-activated protein kinase regulation of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha. Such modulations contribute to cell adaptation and remodeling of muscle fiber type in response to exercise. Despite great improvement in this field, there are still several unanswered questions as well as unfixed issues concerning clinical trials' biases and limitations. Nevertheless, designing multicenter standard clinical trials while considering individual variability and the exercise modality and duration will improve the perspective we have on the mechanisms mediating adaptation to exercise and final outcomes.

Probabilistic carcinogenic and non-carcinogenic risk assessment of heavy metal ingestion through consumption of different walnut cultivars: An Iranian study.

The heavy metal levels in six walnut cultivars from five geographical zones of Iran were measured. An assessment of risks was conducted by calculating the Target Hazard Quotient (THQ) and Incremental Lifetime Cancer Risk (ILCR) by use of the Monte Carlo simulation method. The highest amounts of As and Pb were reported in Farouj samples. Also, the highest levels of Cr, Zn, Cu and Mn were determined in samples collected from Tuyserkan. Accordingly, 50th and 95th ILCRs for general population due to consumption of walnut were 1.03 × 10-4 and 3.11 × 10-4 (for As), 4.10 × 10-6 and 1.1 × 10-5 (for Cr) and 4.71 × 10-9 and 1.05 × 10-8 (for Pb), respectively. In addition, the 50th and 95th centiles of the HIs for walnut ingestion by Iranians were 1.02 and 2.05, respectively, indicating a minor chance of non-cancer effects. Based on the calculated 95% ILCR, dietary exposure to As through the consumption of walnut poses a risk to Iranian consumer health. However, ILCR values of other heavy metals (HMs) were in acceptable ranges (ILCR < 1 × 10-4), representing no toxicological concern for consumers. The most significantly influential parameters were determined by sensitivity analysis during the MCS. According to THQ and ILCR methods, concentration was the most sensitive parameters. For THQ method the concentration effects were ranged from 72.4 to 85.1%. Moreover, for ILCR method the effects of concentration in As, Cr, and Pb were 87.1, 79.1 and 83.54%, respectively.

Application of a neural interface for restoration of leg movements: Intra-spinal stimulation using the brain electrical activity in spinally injured rabbits.

This study aimed to design a neural interface that extracts movement commands from the brain to generate appropriate intra-spinal stimulation to restore leg movement. This study comprised four steps: (1) Recording electrocorticographic (ECoG) signals and corresponding leg movements in different trials. (2) Partial laminectomy to induce spinal cord injury (SCI) and detect motor modules in the spinal cord. (3) Delivering appropriate intra-spinal stimulation to the motor modules for restoration of the movements to those documented before SCI. (4) Development of a neural interface created by sparse linear regression (SLiR) model to detect movement commands transmitted from the brain to the modules. Correlation coefficient (CC) and normalized root mean square (NRMS) error was calculated to evaluate the neural interface effectiveness. It was found that by stimulating detected spinal cord modules, joint angle evaluated before SCI was not significantly different from that of post-SCI (P > 0.05). Based on results of SLiR model, overall CC and NRMS values were 0.63 ± 0.14 and 0.34 ± 0.16 (mean ± SD), respectively. These results indicated that ECoG data contained information about intra-spinal stimulations and the developed neural interface could produce intra-spinal stimulation based on ECoG data, for restoration of leg movements after SCI.

Coronatine elicitation alters chemical composition and biological properties of cumin seed essential oil.

The present experiment evaluated how coronatine (COR) elicitation affects chemical and biological properties of cumin (Cuminum cyminum L.) seed essential oil (CSEO). Following isolation of the EO, its chemical composition was analyzed by gas chromatography-mass spectrometry; also, its bioactivities in terms of antimicrobial/antifungal, cytotoxic (measured by MTT assay) and antioxidant effects (evaluated by DPPH, ß-carotene bleaching (BCB) and TBARS methods) were evaluated. COR-elicitation significantly increased CSEO yield and the level of its chemical components, especially cumin aldehyde which is the main component of CSEO. Results showed that COR-elicitation significantly reduced the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of CSEO against 4 Gram-positive and 3 Gram-negative bacteria and 2 fungi. Moreover, elicitation markedly enhanced the antioxidant and in vitro cytotoxic activity of CSEO. Therefore, COR may be regarded as a useful biotic elicitor for improving EO chemical and biological properties.

Risk factors of premature coronary artery disease in Iran: A systematic review and meta-analysis.

BACKGROUND: The aim of this study was to determine the mean age at which coronary artery disease (CAD) hase decreased in recent years in Iran. This systematic review and meta-analysis compares the prevalence of different risk factors of premature CAD (PCAD) in patients vs healthy individuals. METHODS: Medline, Web of Science, Embase and Scientific Information Database were searched for studies about PCAD risk factors in Iran until 28 October 2017. Observational studies of Iranians, comparing risk factors between patients with PCAD and age- and sex-matched healthy subjects, were included. Fixed-effects and random-effects model were used for pooling data. Odds ratio (OR) with 95% CI and mean difference were used for effect size estimation among studies. RESULTS: Twelve studies were eligible for meta-analysis. Diabetes mellitus (OR: 2.4, 95% CI: 1.9-3.03; P = 0.0001, I2  = 25.5%; P = 0.2), family history of CAD (OR: 2.09, 95% CI: 1.22-3.6; P = 0.007, I2  = 86%; P = 0.0001), dyslipidaemia (OR: 2.05, 95% CI: 1.15-3.64; P = 0.01, I2  = 54%; P = 0.08), smoking (OR: 1.65, 95% CI: 1.11-2.46; P = 0.01, I2  = 77.2%; P = 0.000) and hypertension (OR: 1.35, 95% CI: 1.21 to-1.50; P < 0.001, I2  = 31%, P = 0.1) associated with PCAD. Sensitivity analysis demonstrated that patients with PCAD had significantly lower levels of high-density lipoprotein (HDL) cholesterol and significantly higher levels of triglycerides compared to healthy subjects (MD: -2.56, 95% CI: -3.54 to -1.58, P < 0.001, I2  = 42%, P = 0.01 and MD: 21.17, 95% CI: 14.73-27.62, P < 0.001, I2  = 80.12%, P < 0.001, respectively). It should be noted that although high levels of heterogeneity in LDL and HDL values among the studies were observed, when dyslipidaemia was studied as a binary variable, no significant heterogeneity among studies was observed. CONCLUSION: Diabetes mellitus, family history of CAD, dyslipidaemia, smoking, and hypertension were significantly and positively associated with CAD in young adults compared to healthy age- and sex-matched population in Iran.

Crocin improves renal function by declining Nox-4, IL-18, and p53 expression levels in an experimental model of diabetic nephropathy.

Oxidative damage, inflammation and apoptosis play significant roles in diabetic nephropathy. Previous studies demonstrated anti-inflammatory and anti-oxidative effects of crocin, but there is no evidence about its effects on IL-18, NOX-4, and p53 expression in diabetic kidneys. The aim of this study was to evaluate possible effects of crocin on improving main mechanisms underlying diabetic nephropathy. Male Wistar rats were randomly divided into four separate groups as normal (C), normal treated (CC), diabetic (D), and diabetic treated (DC) (n = 6). Diabetes was induced by a single dose of streptozotocin (40 mg/kg/intravenous). Treated groups received crocin (40 mg/kg, intraperitoneal) for 8 weeks. At the end of the 8th week of the study, all rats were sacrificed and urine, blood and tissue were collected. Levels of urea, uric acid, creatinine and glucose were determined collected sera, and proteinuria was measured in urine samples. Moreover, the contents of malondialdehyde (MDA), nitrate, and glutathione (GLT) as well as catalase (CAT) and superoxide dismutase (SOD) enzymes activities were measured. The expression of NOX-4, IL-18, and p53 at both mRNA and protein levels were also assessed. Hyperglycemia significantly increased proteinuria in diabetic rats (D). Also, depressed antioxidant defense system potency, but increased NOX-4 expression and free radicals production resulting in oxidative stress, were observed. Moreover, expressions of IL-18 (as a marker of inflammation) and p53 (as a marker of apoptosis) were increased. These outcomes were accompanied by enhanced histological damages and renal failure but, treatment with crocin improved these deteriorations, and ameliorated renal function. It potentiated renal cells antioxidant defense system and declined inflammation. Also, crocin lowered apoptosis and improved histological damages in renal cells. Oxidative stress, inflammation and apoptosis are considered three main mechanisms underlying diabetic nephropathy. Treatment with crocin prevented these deleterious effects and improved renal function under diabetic conditions.

Fenofibrate improves renal function by amelioration of NOX-4, IL-18, and p53 expression in an experimental model of diabetic nephropathy.

Among several pathological mechanisms involved in diabetic nephropathy, oxidative stress, inflammation, and apoptosis play a prominent role. Fenofibrate, a peroxisome proliferator-activated receptor-α (PPAR-α) agonist, has markedly improved oxidative stress and inflammatory responses, but there is no evidence about its effects on interleukin-18 (IL-18), NADPH oxidase type 4 (NOX-4), and p53 expression in diabetic kidneys. The aim of this study was to evaluate possible effects of fenofibrate on improving the underlying mechanisms of diabetic nephropathy. Male Wistar rats were randomly divided into four groups namely, normal, normal treated, diabetic and diabetic treated (N = 6). Diabetes was induced by a single dose of streptozotocin (40 mg/kg; IV). Treated animals received fenofibrate for 8 weeks daily (80 mg/kg; po). All groups were sacrificed on day 56 and blood, urine, and tissue samples were collected. Serum levels of urea, uric acid, creatinine, and glucose were assessed. Then, serum levels of malondialdehyde (MDA), nitrate, and glutathione (GLT), as well as the activities of catalase (CAT) and superoxide dismutase (SOD) enzymes were measured. The expression level of NOX-4, IL-18, and p53 proteins at both mRNA and protein levels were evaluated. Diabetes significantly increased albuminuria, free radicals production, inflammation, and apoptosis in non-treated rats while lowered antioxidant capacity. Moreover, diabetes caused histological damages leading to renal failure. Treatment with fenofibrate improved renal function by improving creatinine clearance (P = 0.01) and protein excretion (P = 0.001) and lowering plasma levels of blood urea nitrogen (P = 0.001), creatinine (P = 0.001), and uric acid (P = 0.01). Fenofibrate potentiated antioxidant defense systems by enhancing CAT (P = 0.01) and SOD (P = 0.01) enzymes activities and GLT content (P = 0.01), and reduced oxidative damage by lowering MDA generation (P = 0.02). Fenofibrate also attenuated the expression of NOX-4 (P = 0.05), IL-18 (P = 0.05), and p53 (P = 0.05) at both mRNA and protein levels. In conclusion, treatment with fenofibrate improved renal function by suppression of oxidative stress, attenuation of inflammation, and inhibition of apoptosis.

Oxidative stress induces renal failure: A review of possible molecular pathways.

It has been reported that oxidative stress has a pivotal role in many disorders such as chronic kidney diseases. Free radicals can directly attack cellular elements, trigger intracellular signaling pathways, or induce systemic responses leading to renal damages. In the current review, we evaluated the literature focusing on the main recognized effects of oxidative stress on the pathophysiology of chronic renal disorders. We searched the PubMed-Medline and Scopus databases by using the following key words: oxidative stress, kidney, chronic kidney diseases, and free radicals and found about 200 related articles. Then, we focused on the molecular mechanisms underlying chronic kidney diseases which can be induced by oxidative stress and explored how free radicals stimulate these mechanisms. By reviewing the literature, we found that there are almost nine important molecular pathways through which free radicals influence the renal function. Based on the retrieved data, oxidative stress has an important role in the pathophysiology of chronic kidney diseases. Understanding these pathophysiologic pathways may lead us to find new approaches for the management of these debilitating disorders.

Pesticides and cardiotoxicity. Where do we stand?

Cardiovascular diseases are among the most significant causes of mortality in humans. Pesticides toxicity and risk for human health are controlled at a European level through a well-developed regulatory network, but cardiotoxicity is not described as a separate hazard class. Specific classification criteria should be developed within the frame of Regulation (EC) No 1272/2008 in order to classify chemicals as cardiotoxic, if applicable to avoid long-term cardiovascular complications. The aim of this study was to review the cardiac pathology and function impairment due to exposure to pesticides (i.e. organophosphates, organothiophisphates, organochlorines, carbamates, pyrethroids, dipyridyl herbicides, triazoles, triazines) based on both animal and human data. The majority of human data on cardiotoxicity of pesticides come from poisoning cases and epidemiological data. Several cardiovascular complications have been reported in animal models including electrocardiogram abnormalities, myocardial infarction, impaired systolic and diastolic performance, functional remodeling and histopathological findings, such as haemorrhage, vacuolisation, signs of apoptosis and degeneration.