Pharmacology最新文献

Introduction: Ivermectin (IVM) is a broad-spectrum anti-parasitic agent with potential antibacterial, antiviral, and anti-cancer effects. There are limited studies on the effects of IVM on cardiovascular diseases, so the present study sought to determine the effects of pre-treatment with IVM on myocardial ischemia in both ex vivo and in vivo.

Methods: In the ex vivo part, two groups of control and treated rats with IVM (0.2 mg/kg) were examined for cardiac function and arrhythmias by isolated heart perfusion. In the in vivo part, four groups, namely, control, IVM, Iso (MI), and Iso + IVM 0.2 mg/kg were used. Subcutaneous injection of isoproterenol (100 mg/kg/day) for 2 consecutive days was used for the induction of myocardial infarction (MI) in male Wistar rats. Then electrocardiogram, hemodynamic factors, cardiac hypertrophy, and malondialdehyde (MDA) levels were investigated.

Results: The ex vivo results showed that administration of IVM induces cardiac arrhythmia and decreases the left ventricular maximal rate of pressure increase (contractility) and maximal rate of pressure decline (relaxation). The isoproterenol-induced MI model used as an in vivo model showed that cardiac hypertrophy were increased with no improvement in the hemodynamic and electrocardiogram pattern in the IVM-treated group in comparison to MI (Iso) group. However, the MDA level was lower in the IVM-treated group.

Conclusion: IVM pre-treatment demonstrates detrimental effects in cardiac ischemia through exacerbation of cardiac arrhythmia, myocardial dysfunction, and increased cardiac hypertrophy. Therefore, the use of IVM in ischemic heart patients should be done with great caution.

Introduction: Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities.

Method: This study aimed to evaluate the in vitro spasmolytic and in vivo anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV).

Results: In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes.

Conclusions: These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.

Introduction: The Italian Medicines Agency indicates that about 5% of hospital admissions are due to adverse drug reactions (ADRs). Several factors are recognized to be associated with an increased risk for ADRs, such as the female gender and polytherapy. The aim of this study was to retrospectively analyze the suspected ADRs reported by patients during the anamnestic interview at the Allergy Unit.

Patients and methods: ALLERG-RAF study is a retrospective analysis of the medical records of patients evaluated in the Allergy Unit of ASST Spedali Civili and the University of Brescia from 2000 to 2016. The inclusion criteria were age ≥18 years and medical consultation requested for suspected ADRs. Data relating to the patient's intrinsic characteristics, the drug supposed to be the cause, and the prescribed pharmacological therapy were collected. Pseudonymized data from each patient were collected in an informatics database.

Results: From 2000 to 2016, 35,817 accesses to the Allergy Unit were made, and 2,171 unique events related to a suspected ADR were collected in 1,840 patients. More than two-thirds of the reports concerned females (70.4%). Antibiotics were involved in the majority of the self-reported suspected ADRs (48.7%), particularly beta-lactams (61.1%). Anti-inflammatory drugs, mainly NSAIDs, were second in incidence and suspected in 25.2% of reports. As a site of ADR manifestation, most of the reported reactions involve the skin. No clinical sequelae were reported.

Conclusions: Our results underline the importance of patient reporting in pharmacovigilance. Furthermore, gender gap data emphasizes the importance of the gender-specific medicine approach.

Introduction: The aim of this study was to investigate the effect and mechanism of kaempferol on alcoholic steatohepatitis.

Methods: C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. Kaempferol was given as the interventional drug to chronic alcohol-fed mice for 6 weeks to assess its effects. In vitro, intestinal epithelial Caco-2 cells were stimulated by alcohol, and miRNA-155 mimics were used to further study the effect of kaempferol to miRNA-155 signaling in intestinal epithelial cells. HE staining and oil red O staining were used to observe the liver and intestinal tissue damage in each group of mice, and ALT, AST, IL-1β, and TNF-α were detected by kits; lipopolysaccharide (LPS) expression was detected by ELISA kit, and the expression of IL-1β and TNF-α was assessed by qRT-PCR; Western blot was utilized to assess the excessive inflammatory response of liver and colon tissue and the related signaling pathway activation.

Results: Kaempferol treatment significantly improved pathological changes such as steatosis and vacuolated lesions in liver tissue of the alcohol diet model group, and reduced serum ALT and AST enzyme activities and liver tissue interleukin-1β and tumor necrosis factor-α mRNA expression levels. Kaempferol significantly reduced the expression of miRNA-155 in the intestinal tissue of alcohol-fed mice, significantly increased their cytokine suppressor signaling 1 (SOCS1) protein expression, inhibited the activation of nuclear factor kappa-B and significantly increased the production of the intestinal tight junction proteins occludin and zonula occludens-1. More importantly, kaempferol significantly reduced serum LPS levels in alcoholic steatohepatitis mice. In vitro experiments showed that compared with the control group, kaempferol significantly inhibited the expression level of miRNA-155 in Caco-2 cells under ethanol exposure, decreased the activation of nuclear factor kappa-B, led to an increase in the expression of SOCS1 protein, and increased the production level of occludin protein in Caco-2 cells under the effect of alcohol. In contrast, overexpression of miRNA-155 significantly decreased occludin and SOCS1 protein production and increased nuclear factor kappa-B activation levels in Caco-2 cells, and the administration of kaempferol significantly inhibited this effect.

Conclusion: Kaempferol improved the stability of gut barrier function to ameliorate hepatic injury induced by alcohol intake through enhancing occludin protein expression, by targeting miR-155 to inhibit the excessive inflammatory response in the intestine.

The nucleus basalis of Meynert (nBM) is the major source of cholinergic neurons in the basal forebrain, which require nerve growth factor (NGF) for their survival. Melatonin, a pleiotropic hormone, has been shown to exert neuroprotection in several experimental models, but its effect on nBM neurons is not well known. Thus, the aim of this study is to evaluate the effect of melatonin in organotypic brain slices of the nBM. Organotypic nBM slices were incubated for 2 weeks without (control) or with 100 ng/mL NGF, 1 μM melatonin, or a combination of both. Cholinergic neurons were immunohistochemically stained for choline acetyltransferase (ChAT) and subjected to a co-localization study with silent information regulator 1 (SIRT1) and melatonin receptor 1A (MT1A), both potentially involved in melatonin neuroprotection. Counting of ChAT-positive neurons in nBM slices showed that melatonin and NGF significantly increased the number of ChAT-positive neurons compared to the control in a dose-dependent manner (1-10 μM). In co-treatment with NGF, melatonin did not potentiate the maximal NGF-mediated effect. Immunohistochemical analysis proved that cholinergic nBM neurons co-localized with SIRT1 and MT1A receptor. Our data show that melatonin improves the survival of cholinergic nBM neurons and confirm that they express SIRT1 and MT1A.

Introduction: Artemisia argyi polysaccharide (AAP) has a beneficial effect on menstruation-related symptoms and the potential regulation of lipid metabolism. It is expected to be a safe and effective ingredient for estrogen deficiency and lipid metabolic disorders. Here, we investigate the effect of AAP on body weight gain, estrogen level, and blood lipid changes in ovariectomized (OVX) rats.

Methods: Thirty-six female Wistar rats were randomly divided into six treatment groups, including a sham-operated (Sham) group, OVX group, estrogen replacement (OVX + E2) group, and AAP treatment (OVX + 125, 250, 500 mg/kg AAP) group. The body weight and feed intake were recorded every week. The level of estrogen and blood lipid was determined. The gene expressions and protein expressions of estrogen receptors (ERs), fatty acid synthetase (FAS), acetyl CoA carboxylase 2 (ACC2), and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) were determined.

Results: AAP treatment significantly decreased the body weight gain and average daily food intake of rats in the OVX group. Treatment with AAP significantly increased the relative weight of the uterus, plasma estrogen level, and the gene expression and protein expression of ER-α in the uterus. For blood lipids, plasma levels of triglyceride, total cholesterol, and low-density lipoprotein cholesterol were significantly reduced by AAP treatment in OVX rats. AAP treatment decreased the expression of FAS and HMGR in the liver of OVX rats. Furthermore, AAP treatment significantly increased the gene expression of ACC2, the protein expression of P-ACC2, and the ratio of P-ACC2/ACC2.

Conclusion: In summary, AAP treatment exerts beneficial effects on body weight gain and lipid metabolism disorder induced by ovariectomy through increasing estrogen levels, inhibiting FAS, and promoting fatty acid oxidation.