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Multidrug pain control can be beneficial in relieving pain and limiting narcotic use in renal colic. The purpose of this study was to evaluate the effects of adding dexamethasone to ketorolac on pain control in acute renal colic.One hundred twenty patients with renal colic were randomized into comparison and intervention groups to investigate the effect of 8 mg of dexamethasone with 30 mg ketorolac administered immediately after the patient's admission. The primary outcome was pain intensity based on the visual analog scale (VAS), which was assessed at the baseline and after 30 and 60 min of drugs treatment. Also, grade of vomiting and narcotic or antiemetic requirement were measured at the baseline and after the 60-min intervention.A total of 120 patients were included in the final analysis, with 60 patients (50%) randomized to the comparison group (just ketorolac) and 60 (50%) randomized to the intervention group (ketorolac + dexamethasone). There were no significant demographic differences between groups (P0.05 for all). Differences in VAS scores were significantly lower in the intervention group after 30 min of drug administration (P = 0.009, compared with the control). However, there was not a significant difference in the median VAS score between groups at the baseline and end of the study (P0.05). At the end of the study, the percent of patients who need to narcotics (35% vs. 58%, P = 0.01) and/or antiemetic (12% vs. 28%, P = 0.022) were significantly lower in the intervention group compared with the controls.In comparison with the patients who just received ketorolac, adding dexamethasone provided improved pain control after 30 min of therapy. Furthermore, it decreased opioid requirements and decreased an antiemetic need at the end of the study. Dexamethasone should be considered an important multimodal adjunct for controlling pain and nausea in renal colic.

As statins decrease the progression of sepsis and its related mortality, this study aimed to evaluate the effect of atorvastatin on survival and symptom improvement in hospitalized patients with COVID-19. This randomized controlled trial was performed on 156 hospitalized patients with COVID-19 in Bojnourd city in 2021. Patients were randomly divided into comparison (standard therapy: hydroxychloroquine + Kaletra®) and intervention groups (atorvastatin 20 mg, SD, plus standard therapy). The main outcomes were the rate of symptom improvement, duration of hospitalization, need for intubation, and mortality rate. In this study, seven patients died, two patients (2.6%) in the comparison group and five (6.6%) in the intervention group. The mean hospitalization days (p = 0.001), the pulse rate (p = 0.004), and the frequency of hospitalization in the ICU ward (18.4% vs. 1.3%) were longer and greater in the intervention group. The remission probability in the comparison group was greater (p = 0.0001). The median hospitalization days in the intervention group was longer (p 0.001) and remission in the comparison group occurred 1.71 times sooner (hazard ratio = 1.70, 95% confidence interval = 1.22-2.38, p = 0.002). Totally, adding atorvastatin to the standard regime in this study increased hospitalization days and imposed negative effects on symptom improvement in hospitalized patients with COVID-19.

The main adverse effect of doxorubicin is cardiotoxicity. Oxidative stress and apoptosis induction have been suggested as mechanisms involved in its cardiotoxicity. In this study, cardioprotective effects of alpha-mangostin against doxorubicin-induced cardiotoxicity have been investigated in rats. Forty-two rats were divided as follows: Control, doxorubicin (2 mg/kg every 48 hr), alpha-mangostin (200 mg/kg), alpha-mangostin (50, 100, 200 mg/kg) + doxorubicin (2 mg/kg every 48 hr), and vitamin E (200 IU/kg) + doxorubicin (2 mg/kg every 48 hr). Alpha-mangostin was administered by gavage for 19 days, while doxorubicin (12 days) and vitamin E (19 days) were injected intraperitoneally. Doxorubicin decreased heart rate, increased electrocardiogram signal components duration and reduced systolic and diastolic arterial blood pressure, and caused histological damage in the heart of rats. Doxorubicin decreased heart weight and heart/body weight ratio, as well as elevated creatine phosphokinase isoenzyme and lactate dehydrogenase. Doxorubicin increased malondialdehyde, inflammatory biomarkers, and caspases 3 and 9 and decreased reduced glutathione content in heart tissue but co-administration of alpha-mangostin (100 mg/kg) restored all doxorubicin toxic effects. Results show that alpha-mangostin has protective effects against doxorubicin-induced cardiotoxicity by antioxidant, antiinflammatory, and antiapoptotic effects that may ameliorate doxorubicin cardiotoxicity in human chemotherapy without reduction in its anticancer effect.

Olanzapine, an atypical antipsychotic medication, has been associated with weight gain and metabolic toxicity, especially in long term usage. Carnosic acid (CA), a major constituent of rosemary extract, has been shown to improve metabolic abnormalities. In this experiment, the effect of CA on olanzapine-induced obesity and metabolic toxicity has been evaluated. Female Wistar rats were divided into six groups. (1) control; (2) olanzapine (5 mg/kg/day, IP); (3, 4 and 5) olanzapine (5 mg/kg/day, IP) plus CA (5, 10 and 20 mg/kg/day, gavage) and (6) CA (20 mg/kg/day, gavage). Bodyweight and food intake were measured during the study. After 14 days, mean systolic blood pressure (MSBP), glycemia, serum lipid profile, the serum concentration of leptin, insulin, AMPK, P-AMPK, and P-ACC liver protein levels were evaluated. The mean weight in the group received olanzapine increased by 4.8 g at the end of the study. The average food intake was increased by olanzapine. Olanzapine increased triglyceride, fasting blood glucose (FBG), and leptin levels. It increased MSBP and down-regulated P-AMPK/AMPK ratio and P-ACC protein levels. CA (three doses) decreased body weight gain and reduced average food intake at 10 and 20 mg/kg. CA especially at the highest dose decreased the changes in lipid profile, FBG, leptin level, and MSBP. P-AMPK/AMPK and P-ACC protein levels were increased by carnosic acid. In conclusion, the activation of AMPK by CA can be proposed as a key mechanism against olanzapine-induced metabolic toxicity where the activation of AMPK increases fat consumption and regulates glucose hemostasis in the liver.

This study was designed to assess bisphenol A (BPA)-induced vascular toxicity, the effectiveness of green tea extract and epigallocatechin gallate (EGCG) against BPA toxicity, and possible underlying mechanisms. In isolated rat aorta, contractile and relaxant responses as well as malondialdehyde levels were evaluated. Cell viability and effects on the protein levels of apoptotic (bax, bcl2, and caspase-3), autophagic (LC3), and cell adhesion molecules were calculated using the MTT method and western blotting in human umbilical vein endothelial cells (HUVECs). BPA increased aorta MDA levels (p < .0001) and decreased vascular responses to KCl [20 and 40 mM (p < .0001), 80 mM (p < .001)], phenylephrine [10-8 , 10-6 , and 10-5 M (p < .001), 10-7 and 10-4 M (p < .0001)], and acetylcholine [10-6 M (p < .01), 10-5 and 10-4 M (p < .0001)]. In HUVECs, BPA enhanced the levels of LC3A/B, bax/bcl2 ratio, cleaved caspase-3, and vascular cell adhesion molecule-1. Green tea extract, EGCG, and vitamin E co-treatment with BPA diminished the toxic effects of BPA. These findings provide evidence that green tea extract and EGCG possess beneficial effects in preventing BPA-induced vascular toxicity through increasing the antioxidant activities and the regulation of signaling pathways.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is the reason for this ongoing pandemic infection diseases termed coronavirus disease 2019 (COVID-19) that has emerged since early December 2019 in Wuhan City, Hubei Province, China. In this century, it is the worst threat to international health and the economy. After 4 months of COVID-19 outbreak, there is no certain and approved medicine against it. In this public health emergency, it makes sense to investigate the possible effects of old drugs and find drug repositioning that is efficient, economical, and riskless process. Old drugs that may be effective are from different pharmacological categories, antimalarials, anthelmintics, anti-protozoal, anti-HIVs, anti-influenza, anti-hepacivirus, antineoplastics, neutralizing antibodies, immunoglobulins, and interferons. In vitro, in vivo, or preliminary trials of these drugs in the treatment of COVID-19 have been encouraging, leading to new research projects and trials to find the best drug/s. In this review, we discuss the possible mechanisms of these drugs against COVID-19. Also, it should be mentioned that in this manuscript, we discuss preliminary rationales; however, clinical trial evidence is needed to prove them. COVID-19 therapy must be based on expert clinical experience and published literature and guidelines from major health organizations. Moreover, herein, we describe current evidence that may be changed in the future.

Introduction: The present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of TLR4 and pro-inflammatory cytokine in rats. Methods: Male Wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. TLR4 and MyD 88 expression and levels tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured in the heart and serum. Results: Oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (LDL) (263 ± 13 ng/dL) than the cholesterol-fed animals (98 ± 8 ng/dL; P Conclusion: These findings suggest that cardiac TLR4 is preferentially upregulated by oxidized cholesterol in rats. Oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.

Doxorubicin (DOX) is an anticancer medicine that may trigger cardiomyopathy. Rosmarinic acid (RA) has shown antioxidant, anti-inflammatory, and anticancer effects. This investigation assessed the cardioprotective effect of RA on DOX-induced-toxicity in both in vivo and in vitro experiments. Male rats were randomized on 7 groups: (1) control, (2) DOX (2 mg/kg, per 48 h, 12d, i.p), (3) RA (40 mg/kg, 12d, i.p.), (4-6) RA (10, 20, 40 mg/kg, 16d, i.p.)+ DOX, (7) Vitamin E (200 mg/kg, per 48 h, 16d, i.p.) + DOX and then indices of cardiac function were estimated. Also, DOX and rosmarinic acid effects were examined on MCF7 cells (breast cancer cells line) to clarify that both cardiotoxicity and anticancer effects were analyzed. DOX increased heart to body weight ratio, RRI, QA, STI, QRS duration and voltage, attenuated HR, blood pressure, Max dP/dt, Min dP/dt, LVDP, enhanced MDA, declined GSH amount, and caused fibrosis and necrosis in cardiac tissue. Administration of RA ameliorated the toxic effects of DOX. In vitro studies showed that RA did not affect the cytotoxic effect of DOX. RA as an antioxidant, anti-inflammatory, and cardioprotective compound could be a promising compound to help minimize DOX-induced cardiotoxicity.

OBJECTIVES: Despite advances in our understanding of metabolic syndrome (MetS) and the treatment of each of its components separately, currently there is no single therapy approved to manage it as a single condition. Since multi-drug treatment increases drug interactions, decreases patient compliance and increases health costs, it is important to introduce single therapies that improve all of the MetS components. EVIDENCE ACQUISITION: We conducted a PubMed, Scopus, Google Scholar, Web of Science, US FDA, utdo.ir and clinicaltrial.gov search, gathered the most relevant preclinical and clinical studies that have been published since 2010, and discussed the beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors to prevent and treat different constituent of the MetS as a single therapy. Furthermore, the pharmacology of DPP-4 inhibitors, focusing on pharmacodynamics, pharmacokinetics, drug interactions and their side effects are also reviewed. RESULTS: DPP-4 inhibitors or gliptins are a new class of oral anti-diabetic drugs that seem safe drugs with no severe side effects, commonly GI disturbance, infection and inflammatory bowel disease. They increase mass and function of pancreatic β-cells, and insulin sensitivity in liver, muscle and adipose tissue. It has been noted that gliptin therapy decreases dyslipidemia. DPP-4 inhibitors increase fatty oxidation, and cholesterol efflux, and decrease hepatic triglyceride synthase and de novo lipogenesis. They delay gastric emptying time and lead to satiety. Besides, gliptin therapy has anti-inflammatory and anti-atherogenic impacts, and improves endothelial function and reduces vascular stiffness. CONCLUSION: The gathered data prove the efficacy of DPP-4 inhibitors in managing MetS in some levels beyond anti-diabetic effects. This review could be a lead for designing new DPP-4 inhibitors with greatest effects on MetS in future. Introducing drugs with polypharmacologic effects could increase the patient’s compliance and decrease the health cost that there is not in multi-drug therapy. [Figure: see text]

The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg-1 ·day-1 , gavage) plus resveratrol (25, 50, and 100 mg·kg-1 ·day-1 , i.p.) or GSE (3, 6, 12 mg·kg-1 ·day-1 , i.p.) or vitamin E (200 IU/kg/every other day, i.p.). After 2 months, mean systolic blood pressure, serum lipid profile, glycaemia, and fat index were examined. By enzyme-linked immunosorbent assay, the serum concentrations of insulin, leptin, adiponectin, and paraoxonase 1, and by real-time polymerase chain reaction as well as western blotting, key liver elements in cholesterol hemostasis (LDLR, CYP7A1, ABCG5 and 8) and insulin signaling (p-Akt/Akt and p-PI3K/PI3K) were measured. BPA increased mean systolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol and reduced paraoxonase1 and the hepatic expression of both ABCG5 and ABCG8. It increased the body fat index, leptin, adiponectin, insulin, and glycaemia level and decreased the hepatic protein expression of p-Akt/Akt and p-PI3K/PI3k. GSE, resveratrol, or vitamin E coadministration along with BPA restored the detrimental effects of BPA in some levels. Herein, the predisposing effects of BPA-induced metabolic syndrome were restored by GSE and resveratrol, linked to the regulation of insulin signaling, ABCG8 expression, and their antioxidant properties.

Ginseng, Panax ginseng, has been used for various diseases and proven its great efficacy in managing central nervous system diseases.This article covers the therapeutic potential of patents on ginseng and its active constituents to develop therapies for neurodegenerative and neurological disorders, since 2010. The literature review was provided using multiple search engines including Google Patent, Espacenet and US Patent in the field of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, cognitive, and neurological disorders.The gathered data represented outstanding merits of ginseng in treatment of neurodegenerative and neurological disorders. These effects have been mediated by neurogenesis, anti-apoptotic and antioxidant properties, inhibition of mitochondrial dysfunction, receptor-operated Ca

Aims During heart ischemia, the lack of oxygen in the myocardial cells causes pH and ion disturbances and cell death through opening mitochondrial permeability transition pores (mPTP). Considering the inhibitory effects of mitochondrial ATP-dependent potassium channels (mt-KATP) on these pores and anti-ischemic effects of morin, we hypothesized that it may exert its positive effects via activating mt-KATP as well as its anti-oxidative effects. Main methods Isolated rat hearts were perfused by Krebs-Henseleit solution enriched with the morin (0.25, 0.5 and 1 mg/L) or 5-hydroxydecanoate (5-HD, a mt-KATP blocker;100 μM) or both as needed 5 min before starting regional ischemia till the first 10 min of the reperfusion period. The reperfusion was developed with Krebs-Henseleit solution 60 or 120 min respectively for biochemical evaluations (lactate dehydrogenase and malondialdehyde level) or the assessment of myocardial infarct size. During the experiments, hemodynamic functions were recorded and cardiac arrhythmias were determined. Key findings Our findings demonstrated that morin reduced the infarct size. Also, morin perfusion could remarkably prevent the malondialdehyde over-production during ischemia. Total ventricular ectopic beats had the same significant changes as the malondialdehyde level, in both ischemia and reperfusion phases. Morin could also relatively improve the ischemia-induced hemodynamic dysfunction. All mentioned protective effects of morin were reversed by concomitant perfusion of 5-HD. Significance Morin has protective effects against ischemic hearts through anti-oxidative effects. It also suggests a link between the cardioprotective effects of morin and mt-KATP. However, additional studies are required to prove this preliminary hypothesis.

Drug resistance is worldwide health care crisis which decrease drug efficacy and developing toxicities. Effective resistance detection techniques could alleviate treatment cost and mortality associated with this crisis. In this review, the conventional and modern analysis methods for monitoring of drug resistance are presented. Also, various types of emerging rapid and sensitive techniques including electrochemical, electrical, optical and nano-based methods for the screening of drug resistance were discussed. Applications of various methods for the sensitive and rapid detection of drug resistance are investigated. The review outlines existing key issues in the determination which must be overcome before any of these techniques becomes a feasible method for the rapid detection of drug resistance. In this review, the roles of nanomaterials on development of novel methods for the monitoring of drug resistance were presented. Also, limitations and challenges of conventional and modern methods were discussed.

The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the protective role of grape seed extract (GSE) and resveratrol were investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of GSE and resveratrol. Then, BPA was added to the cells and cell viability and effects on the protein level of cell adhesion molecules were measured through MTT and western blotting. Animals were randomly divided into control, GSE (3 and 12 mg·kg-1 ·day-1 ip), resveratrol (100 mg·kg-1 ·day-1 ip), BPA (35 mg·kg-1 ·day-1 , gavage), BPA plus GSE (3, 6, and 12 mg·kg-1 ·day-1 ip), BPA plus resveratrol (25, 50, and 100 mg·kg-1 ·day-1 ip), and BPA plus vitamin E (200 IU/kg per every other day ip). After 2 months, contractile and relaxant responses were evaluated on the isolated aorta. BPA increased the level of aorta malondialdehyde (p < 0.001) and decreased vascular responses to KCl (p < 0.01), phenylephrine (p < 0.001), and acetylcholine (p < 0.01). In HUVECs, BPA (IC50 : 220 μM) increased protein level of vascular cell adhesion molecule (p < 0.05) and cleaved capase3 (p < 0.001). GSE, resveratrol, and vitamin E cotreatment restored toxic effects of BPA in some levels. BPA vascular toxicity was attributed to lipid peroxidation and endothelial dysfunction. The protective role of GSE and resveratrol against BPA-endothelial dysfunction could be attributed to their potent antioxidant properties.

Many scientific articles proved that green tea (GT), Camellia sinensis, has a great potential to manage central nervous system, cardiovascular, and metabolic diseases and treat cancer and inflammatory disorders. However, it is important to consider that "natural" is not always "safe." Some relevant articles reported side effects of GT, detrimental effects on health. The aim of this study is to provide a classified report about the toxicity of GT and its main constituents in acute, subacute, subchronic, and chronic states. Furthermore, it discusses on the cytotoxicity, genotoxicity, mutagenicity, carcinogenicity, and developmental toxicity of GT and its main constituents. The most important side effects have been reported hepatotoxicity and gastrointestinal disorders specially while consumed on an empty stomach. GT and its main components are not major teratogen, mutagen, or carcinogen substances. However, there is limited data in using them during pregnancy, and they should be used with caution in pregnancy, breast-feeding, and susceptible people. Because GT and its main components have a wide variety of drug interactions, consideration should be taken in coadministration of them with narrow therapeutic indexed drugs. Furthermore, they evoke selective cytotoxicity on cancerous cells that could engage them as an adjuvant substance in cancer therapy.

Background: Coronary artery disease is a leading cause of death worldwide. The present study has been designed to investigate efficacy of methanolic extract of Scrophularia subuphylla (S. subuphylla) on ischemia and reperfusion-induced myocardial injury in isolated rat heart. Methods: The isolated male Wistar rat hearts (n= 5) were perfused by Krebs-Henseleit solution enriched with the extract (0, 1, 5, and 10 μg/ml), using the langendorff method. After 15 minutes stabilization, the hearts were subjected to 30 minutes regional ischemia and then 120 minutes reperfusion. Results: Administration of the extract did not improve any of cardiac markers of flow rate, heart rate and developed pressure. Number, percentage and duration of arrhythmias were not affected by any concentrations of the extract. However, the concentration of 1 and 5 µg/ml increased the VT duration compared to control group (P

Licorice (Glycyrrhiza glabra) has been considered as an herbal drug since ancient time. Nowadays, it is a well-known spice that possesses worth pharmacological effects. However, some relevant articles have revealed negative impacts of licorice in health. By considering the great wishes in using herbal medicine, it is important to show adverse effects of herbal medicine in health. At present, there are misunderstandings toward the safety of herbal medicines. Herein, we gathered scientific research projects on the toxicity effects of licorice and glycyrrhizin to highlight their safety. In this regards, we categorized our findings about the toxicity effects of licorice and glycyrrhizin in acute, sub-acute, sub-chronic, and chronic states. Besides, we discussed on the cytotoxicity, genotoxicity, mutagenicity, and carcinogenicity of licorice and glycyrrhizin as well as their developmental toxicity. This review disclosed that G. glabra and glycyrrhizin salts are moderately toxic. They need to be used with caution during pregnancy. G. glabra and glycyrrhizin possess selective cytotoxic effects on cancerous cells. The most important side effects of licorice and glycyrrhizin are hypertension and hypokalemic-induced secondary disorders. Licorice side effects are increased by hypokalemia, prolonged gastrointestinal transient time, decreased type 2 11-beta-hydroxysteroid dehydrogenase activities, hypertension, anorexia nervosa, old age, and female sex. Copyright © 2017 John Wiley & Sons, Ltd.

Background: Rosmarinic acid is a polyphenolic compound with considerable antioxidant activities. We aimed to investigate its cardioprotective effects against isoproterenol-induced myocardial infarction (MI) in rats. Methods: Male Wistar rats were assigned to 5 groups of control, isoproterenol, and treatments with 10, 20, 40 mg/kg of rosmarinic acid. Myocardial infarction was induced by subcutaneous injection of isoproterenol (100 mg/kg) once daily for 2 days. Rosmarinic acid was injected intraperitoneally once daily for 4 days, from the day of isoproterenol injection. In the fifth day the animals were anesthetized and hemodynamic and electrocardiographic parameters were recorded. After collecting the blood samples, the hearts were removed, weighed immediately to measure the cardiac enlargement, and kept for further histological studies. Lactate dehydrogenase and malondialdehyde were measured in the heart tissues for evaluating the damages and lipid peroxidation, respectively. Results: Rosmarinic acid revealed a considerable antioxidant activity in vitro, with IC50 of 6.43µg/ml. Isoproterenol induced cardiac arrhythmias, myocardial damage and cardiac enlargement. Rosmarinic acid significantly reduced peripheral neutrophil percentage and inhibited isoproterenol-induced ST-segment elevation and R-amplitude depression in the infarcted hearts. It also significantly increased the mean arterial pressure and heart rate and decreased the left ventricular end diastolic pressure. The ventricular contractility was considerably improved by rosmarinic acid. Histopathological evaluations showed that rosmarinic acid significantly diminished the post-MI necrosis and fibrosis in the myocardium and inhibited the cardiac edematous. Conclusion: It is deducible from the results that rosmarinic acid improves the cardiac performance and inhibits post-MI myocardial depression, probably due to its anti-oxidative activity.

Background: The upward desire in using traditional medicine as a remedy for treatment of different diseases has led the scientists to be thoughtful on plants as alternative sources of conventional drugs. Methods: Herein, anti-inflammatory effects of Marrubium vulgare methanolic extract was evaluated in carrageenan- induced paw edema in rats through examining paw thickness, histological studies and myeloperoxidase activity (MPO). The antioxidant activity of M. vulgare extract and its phenolic and flavonoids content were evaluated by folin-Ciocalteau, and aluminum chloride colorimetric assay, separately. Results: The results showed that M. vulgare alleviated paw inflammation as indexed by reduction paw thickness (p

Toxins are natural or chemical poisonous substances with severe side effects on health. Humans are generally exposed by widespread toxic contaminations via air, soil, water, food, fruits and vegetables. Determining a critical antidote agent with extensive effects on different toxins is an ultimate goal for all toxicologists. Traditional medicine is currently perceived as a safe and natural approach against toxins. In this regard, we focused on the protective effects of green tea (Camellia sinensis) and its main components such as catechin, epicatechin, epicatechin gallate, gallocatechin, epigallocatechin and epigallocatechin gallate as a principal source of antioxidants against both natural and chemical toxins. This literate review demonstrates that protective effects of green tea and its constituents were mainly attributed to their anti-oxidative, radical scavenging, chelating, anti-apoptotic properties and modulating inflammatory responses. Although, some studies reveal they have protective effects by increasing toxin metabolism and neutralizing PLA2, proteases, hyaluronidase and l-amino acid oxidase enzymes.

Diabetic nephropathy as a deleterious complication of diabetes mellitus and an important cause of end-stage renal failure is characterized by changes in the molecular and cellular levels. Cell-cell communication via the gap and tight junctions are involved in the pathogenesis of diseases such as diabetes and kidney failure. Studying cell junctions including gap junctions, tight junctions, and anchoring junctions within the nephron can be used as an early sign of diabetic nephropathy. Furthermore, cell junctions may be an upcoming target by pharmacological methods to improve treatments of diabetic nephropathy and pave the way to introduce promising therapeutic strategies based on cell-cell communications effects and its translation into clinical studies for the treatment of diabetic nephropathy.

The objective of this study was to improve the therapeutic efficacy of methylprednisolone acetate (MPA) in the treatment of rheumatoid arthritis (RA) by incorporating the drug into the hydroxyapatite (HAp) nanoparticles. The nanoparticles were synthesized using a chemical precipitation technique and their size and morphology were evaluated by dynamic light scattering and scanning electron microscopy (SEM). The solid-state behavior of the nanoparticles was also characterized by operating X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The Brunauer–Emmett–Teller and Barrett–Joyner–Halenda N2 adsorption/desorption analyses were also performed to determine the surface area, Vm (the volume of the N2 adsorbed on the one gram of the HAp when the monolayer is complete) and the pore size of the samples. Furthermore, the therapeutic efficacy of the prepared nanoformulation on the adjuvant induced arthritic rats was assessed. HAp mesoporous nanoparticles with a particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 44.53% were obtained. The specific surface area of HAp as well as the Vm values were decreased after the drug loading process. The nanoformulation revealed the slower drug release profile compared to the pure drug. The MTT assay indicated that the MPA-loaded nanoparticles had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines compared to the pure drug. Interestingly, the in vivo study confirmed that the drug-loaded nanoparticles could considerably decrease the paw volume and normalize the hematological abnormalities in the arthritic rats.

Background: Hesperidin is a flavonoid and has strong anti-oxidant and anti-inflammatory activities. The aim of the present study is to investigate the effects of hesperidin on ischemic/reperfusion (I/R) induced injuries and arrhythmias. Methods: Male Wistar rats were anesthetized and then the hearts were removed and cannulated immediately to a langendorff apparatus and prepared for the left coronary artery ligation. The hearts were perfused with Krebs-Henseleit Buffer Solution (KHBS; control) or KHBS plus hesperidin (1, 2.5 & 5µg/ml; treated groups) 5 minutes before coronary occlusion, during the ischemia, and reperfusion period. After reperfusion, double staining strategy (Evans blue and TTC) were used. The percentage of infarct size was determined by Image-j software. Arrhythmia in control group and treated groups were analyzed and compared. Lactate concentration was measured in samples at the end of stabilization, 30 minute after ischemia, and 60 minute after reperfusion. Western blotting was performed for evaluation of pAMPK at the end of the ischemia in the heart tissues. Results: The results demonstrated that hesperidin caused a significant reduction in ventricular ectopic beats (VEBs) number during ischemia and reperfusion phase (p

The current study was aimed to investigate the anti-inflammatory effect of triamcinolone acetonide-loaded hydroxyapatite (TA-loaded HAp) nanocomposites in the arthritic rat model. The HAp nanocomposites were synthesized through a chemical precipitation method and the drug was subsequently incorporated into the nanocomposites using an impregnation method. The physicochemical properties as well as cytotoxicity of the prepared nanoformulation were examined as well. To evaluate the therapeutic efficacy of the prepared nanoformulation, the various parameters such as paw volume, haematological parameters and histological studies were assessed in the arthritic rats. The nanocomposites with the particle size of 70.45 nm, pore size of 2.71 nm and drug loading of 41.94% were obtained in this study. The specific surface area (aBET) as well as the volume of nitrogen adsorbed on one gram of HAp to complete the monolayer adsorption (Vm) were decreased after the drug loading process. The prepared nanoformulation revealed the slower drug release profile compared to the pure drug. Furthermore, the obtained data from MTT assay showed that the TA-loaded nanocomposites had a lower cytotoxic effect on NIH-3T3 and CAOV-4 cell lines as compared to the pure drug. Furthermore, TA-loaded HAp nanocomposites demonstrated favorable effects on the paw volume as well as the haematological and histopathological abnormalities in the adjuvant-induced arthritic rats. Therefore, TA-loaded HAp nanocomposites are potentially suggested for treatment of rheumatoid arthritis after further required evaluations.

Sepsis-induced myocardial dysfunction is a serious organ complication. In the present study, we investigated the effect of metformin on myocardial dysfunction and TLR4 activity in LPS-induced sepsis. Male Wistar rats were randomly divided into 3 groups (n=6): control received normal saline (0.5ml), LPS group received lipopolysaccharide (0.5mg/kg; i.p), and metformin treated group received LPS (0.5mg/kg)+metformin (100mg/kg; i.p). 9h later the hemodynamic parameters were recorded, blood samples were collected, and the hearts were removed and weighted. The concentration of TNF-α, content of MYD88, the phosphorylation of AMPK, and the rate of TLR4 expression in the heart were assessed. In the animals treated with metformin, the preservation of left ventricular function was associated with the reduction of myeloperoxidase activity (31%, P

Activation of AMP‑activated protein kinase (AMPK) has been indicated to produce an anti‑inflammatory effect through the suppression of toll‑like receptor (TLR) activity. In the present study, the investigation was designed to identify the effect of A‑769662, a direct activator of AMPK on lipopolysaccharide (LPS)‑induced acute lung and heart inflammation in rats. To induce inflammation, an intraperitoneal injection of LPS (0.5 mg/kg) was administered to Wistar rats. The inflammatory parameters and AMPK phosphorylation were then measured 9 h later. For the treatment group, A‑769662 (10 mg/kg) was administrated intraperitoneally immediately prior to LPS injection. The results demonstrated that A‑769662 attenuated the LPS‑induced acute inflammation in the heart and lung tissue, as indicated by the significant reduction in myeloperoxidase activity (P

Rat aorta assay provides a low cost and rapid platform, especially for preclinical in vivo models. The signaling pathways of the analog on the vessels could be evaluated separately on the endothelium or smooth muscle cells by rings of the rat aorta in vitro. The rat aorta is used for angiogenesis modeling to integrate the benefits of the both in vivo and in vitro models. These explain the importance and usage of rat aorta in researches. Furthermore, about 4503 articles have been published with the key word "rat aorta" in title or abstract from 1955 until the end of 2013 in Medline. In this review, these articles were organized into two main categories: in vivo and in vitro studies. The in vitro section focused on the rat aorta model, as a tool for evaluate the mechanism of vasodilation, vasoconstriction and angiogenesis. In the in vivo section, the most important usage of this tissue was evaluated. Also, the vasotonic signaling pathways in the vessel are explained briefly and some rat aorta applications in vitro and in vivo have been discussed.

There was a misprint in the title of published article: The Eeffect of Metformin Combined with Calcium-Vitamin D3 Against Diet-Induced Nonalcoholic Fatty Liver Disease. Adv Pharm Bull, 2018, 8(1), 97-105. doi: 10.15171/ apb.2018.012.1 In the title of this article, the word "Eeffect" was corrected to "Effect". The correct title of the article is: The Effect of Metformin Combined with Calcium-Vitamin D3 Against Diet-Induced Nonalcoholic Fatty Liver Disease References Shojaei Zarghani S, Abbaszadeh S, Alizadeh M, Rameshrad M, Garjani A, Soraya H. The Eeffect of Metformin Combined with Calcium-Vitamin D3 Against Diet-Induced Nonalcoholic Fatty Liver Disease. Adv Pharm Bull 2018;8(1):97-105. doi:10.15171/apb.2018.012

The mechanisms of bisphenol-A (BPA)-induced metabolic syndrome as well as the protective role of grape seed extract (GSE) and resveratrol were investigated. Rats were treated with BPA (0 and 35 mg·kg

Myocardial infarction is a common presentation of coronary artery disease and the leading cause of death worldwide. The present study investigated potential resistance to ischemia-reperfusion (I/R) injuries following administration of methanolic (MeOH) extract of Scrophularia frigida (S. frigida) in isolated rat heart. Male Wistar rat hearts (n= 8-10) were isolated and allowed to equilibrate for 20 min, and then subjected to 30 min regional ischemia followed by 120 min reperfusion. In the control group, Krebs-Henseleit (K/H) solution was perfused. However, in the treatment groups K/H solution containing 1, 5, and 10 µg/cc of extract was infused. In addition, total phenol, total flavonoid content and antioxidant property were evaluated and extract was subjected to phytochemical analysis. Administration of extract improved the flow rate, developed pressure as well as max and min left ventricular dp/dt. Number and duration of VT were significantly reduced by all extract concentrations in ischemic phase. In reperfusion phase, significant decreases in single and total arrhythmias were seen. Furthermore, concentrations of 5 and 10 µg/cc of extract remarkably decreased the infarct size. Generally, the methanolic extract of S. frigida exhibited a protective effect against I/R-induced injures, which might be due to the antioxidant activiies of iridoids and phenolics.

The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the protective role of grape seed extract (GSE) and resveratrol were investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations of GSE and resveratrol. Then, BPA was added to the cells and cell viability and effects on the protein level of cell adhesion molecules were measured through MTT and western blotting. Animals were randomly divided into control, GSE (3 and 12 mg·kg

The aim of this study was to improve the physicochemical properties as well as therapeutic efficacy of ezetimibe (EZT), through preparation of the solid dispersion (SD). SDs were formulated using polyvinylpyrrolidone K30 (PVP) via solvent method. The physicochemical properties along with in vitro drug release patterns of the prepared SDs were examined. To estimate the therapeutic efficiency of prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were performed. Differential scanning calorimetry (DSC) and powder X-ray diffractometery (PXRD) showed that the drug crystallinity was remarkably decreased during preparation process. Faster drug release pattern of SDs was proved by in vitro dissolution test. Administration the SD of EZT led to a significant decrease in serum total cholesterol (TC) and LDL-C level as well as liver index in hyperlipidemic rats (P

Introduction: Acute treatment with metformin has a cardio-protective effects by suppression of inflammatory responses during myocardial infarction (MI) through activation of AMP-activated protein kinase (AMPK). Neutrophils have a pivotal role during MI-induced inflammatory responses. Some anti-inflammatory treatments have decreased cardiac injury and infarct size in MI. Here we evaluated the effects of chronic pre-treatment with metformin on myocardial remodeling and neutrophil recruitment after isoproterenol-induced MI. Methods: Male wistar rats were randomly assigned into 6 groups (n=6) of untreated control, sham, isoproterenol (Iso), and pre-treated orally with 25, 50, and 100 mg/kg of metformin, twice daily, for 14 days. Isoproterenol was injected subcutaneously (sc) at 13th and 14th days for induction of acute MI. Histopathological examinations were done on the harvested hearts. Number of neutrophils in peripheral blood and their infiltration to myocardium were evaluated by Gimsa staining and myeloperoxidase (MPO) assay, respectively. Results: Histopathological analysis showed a significant attenuation of isoproterenol-induced cardiomyocyte necrosis and fibrosis by all three doses of metformin. The heart to body weight ratio was also decreased with all doses of metformin. Pre-treatment with metformin in comparison to Iso (MI) group reduced peripheral neutrophils (p

Purpose: Metformin is one of the most popular drugs tested against nonalcoholic fatty liver disease (NAFLD). The present study aimed to investigate whether calcium-vitamin D3 cosupplementation will intensify the effect of metformin on the prevention of high-fat, high-fructose (HFFr) diet-induced hepatic steatosis. Methods: Male wistar rats (210±16 g) were assigned into the following seven groups: a Control group to receive a standard chow and six HFFr-fed groups to receive diets containing either normal (0.5% calcium and 1000 IU/kg vitamin D3) or high amount of calcium and vitamin D3 (2.4% calcium and 10000 IU/kg vitamin D3) (CaD), in combination with gastric gavage administration of either saline or 25 or 200 mg/kg body weight/day metformin. After 60 days, rats were assessed with respect to their anthropometric, metabolic and hepatic parameters, as well as their hepatic AMP-activated protein kinase (AMPK) phosphorylation. Results: Metformin and CaD, either alone or in combination, caused a significant reduction in HFFr diet-induced high serum aspartate aminotransferase (AST), hepatic steatosis and lipid accumulation without effect on insulin resistance and AMPK phosphorylation. In addition, slightly (and non-significantly) better effects of the combination in ameliorating steatosis and hepatic cholesterol content were observed. Conclusion: Taken together, our results suggest that metformin and CaD could protect against the onset of HFFr diet-induced NAFLD in an insulin and AMPK-independent manner, without any marked additional benefits of their combination.