Thymoquinone attenuates olanzapine-induced metabolic disorders in rats.

BACKGROUND: Olanzapine (OLZ) is an atypical antipsychotic agent for psychotic disorders. Evidence has shown that OLZ is related to metabolic side effects, including obesity, hypertension, and insulin resistance. Thymoquinone (TQ) is the principal bioactive component of Nigella sativa. Several studies have been conducted to investigate the effectiveness of TQ in alleviating metabolic abnormalities. In the current research work, the protective effects of TQ on metabolic disorders induced by OLZ and possible underlying mechanisms were investigated. METHODS AND RESULTS: Wistar rats were exposed to TQ alone (10 mg/kg), OLZ (5 mg/kg), or OLZ plus TQ (2.5, 5, or 10 mg/kg) given daily by intraperitoneal injection. After the treatment, variations in body weight, food intake, systolic blood pressure, serum leptin, biochemical factors, liver malondialdehyde (MDA), and glutathione (GSH) content were evaluated. Protein expression of AMPK in the liver was also measured by a western blotting test. OLZ increased body weight, food intake, MDA levels, and blood pressure. OLZ also elevated glucose, triglyceride, low-density lipoprotein cholesterol, and leptin serum levels. It decreased GSH. In the western blot, decreased AMPK protein level was obtained. These changes were attenuated by TQ co-administration. CONCLUSIONS: The present study demonstrates the effectiveness of TQ on OLZ-induced metabolic abnormalities related to its antioxidant activity and regulation of glucose homeostasis and lipid metabolism.

Quetiapine attenuates the acquisition of morphine-induced conditioned place preference and reduces ERK phosphorylation in the hippocampus and cerebral cortex.

Background: Quetiapine is an atypical antipsychotic that antagonizes dopamine and serotonin receptors. It has been suggested that quetiapine can be used to treat substance use disorders, including opioid use disorder. Opioids modulate dopaminergic functions associated with conditioned reinforcement and these effects can be measured via the conditioned place preference (CPP) paradigm. Opioids' unconditioned effects are regulated by several proteins, including extracellular signal-regulated kinase (ERK) and cAMP-responsive element-binding (CREB).Objective: To assess the effect of quetiapine on morphine-induced CPP and motor activity levels, and on the levels of ERK and CREB proteins in the hippocampus and cerebral cortex.Methods: 42 male rats were exposed to a CPP protocol, in which they underwent a conditioning paradigm with saline, quetiapine (40 mg/kg), morphine (10 mg/kg), morphine plus quetiapine (10, 20, or 40 mg/kg), or morphine plus memantine (7.5 mg/kg, a positive control drug) (n = 6 per group). The rats were tested for CPP and exploratory activity. Levels of ERK and CREB proteins in the hippocampus and cerebral cortex were also measured.Results: Quetiapine co-administered with morphine inhibited morphine-induced CPP [F (6, 70) = 11.67, p < .001] and morphine's effects on motor activity (p < .001). Morphine enhanced ERK phosphorylation in the hippocampus (p < .001) and cerebral cortex (p < .001), an effect inhibited by quetiapine.Conclusion: Quetiapine attenuates morphine-induced CPP and locomotion and these effects are associated with a reduction of ERK phosphorylation in the hippocampus and cerebral cortex. These results suggest that quetiapine should be further explored as a potential treatment for opioid use disorder.

Potential role of green tea extract and epigallocatechin gallate in preventing bisphenol A-induced metabolic disorders in rats: Biochemical and molecular evidence.

BACKGROUND: Bisphenol A (BPA) is an artificial chemical widely used in the production of polycarbonate plastics and epoxy resins. Accumulating evidence indicates that BPA exposure is associated with metabolic disorders. The beneficial effects of green tea and epigallocatechin gallate (EGCG), major catechin present in green tea, on alleviating BPA-induced metabolic disorders have been shown in various studies. PURPOSE: Protective effects of green tea extract and EGCG on BPA-induced metabolic disorders and possible underlying mechanisms were investigated. METHODS: Rats were randomly divided into control, green tea extract (50 and 100 mg/kg, IP), EGCG (20 and 40 mg/kg, IP), BPA (10 mg/kg, gavage), BPA plus green tea extract (25, 50, and 100 mg/kg, IP), BPA plus EGCG (10, 20, and 40 mg/kg, IP), and BPA plus vitamin E (200 IU/kg, IP). After two months, body weight, blood pressure, biochemical blood tests, hepatic malondialdehyde (MDA), and glutathione (GSH) were assessed. By enzyme-linked immunosorbent assay, serum levels of insulin, leptin, adiponectin, TNFα, and IL-6, and by western blotting, hepatic insulin signaling (IRS-1, PI3K, Akt) were measured. RESULTS: BPA increased body weight, blood pressure, and MDA, decreased GSH, elevated serum levels of low-density lipoprotein cholesterol, total cholesterol, triglyceride, glucose, insulin, leptin, TNFα, IL-6, and liver enzymes including alanine aminotransferase and alkaline phosphatase, and lowered high-density lipoprotein cholesterol and adiponectin levels. In western blot, decreased phosphorylation of IRS-1, PI3K, and Akt was obtained. Administration of green tea extract, EGCG, or vitamin E with BPA reduced the detrimental effects of BPA. CONCLUSION: These findings indicate that green tea extract and EGCG can be effective in preventing or reducing metabolic disorders induced by BPA linked to their antioxidant and anti-inflammatory activity, regulating the metabolism of lipids, and improving insulin signaling pathways.

Evaluation of green tea extract and epigallocatechin gallate effects on bisphenol A-induced vascular toxicity in isolated rat aorta and cytotoxicity in human umbilical vein endothelial cells.

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.

Selective isolation of sesquiterpene coumarins from asafoetida using dummy molecularly imprinted solid phase extraction method.

Due to the biological features of sesquiterpene coumarins and incomparable interest in therapeutics application of natural products, extraction of sesquiterpene coumarins from asafoetida have gained highly attention. One of the most important problems is removal of sulfur containing compounds which are co-existed with sesquiterpene coumarins. So employment of new methods for selective extraction and cleanup of sesquiterpene coumarins is very substantial. In this study using dummy molecularly imprinting technique, 7-hydroxycoumarin-imprited polymer was synthesized and after evaluation of binding properties of polymers, the optimum one was used as sorbent in solid phase extraction. Afterwards dummy molecularly imprinting solid phase extraction (DMISPE) method was calibrated for simultaneous extraction of galbanic acid, 7-isopentenyloxy coumarin and auraptene from aqueous media before high performance liquid chromatography with UV detector (HPLC-UV) analysis. The recovery was in the range of 68.32%-84.69%, which were in the acceptable range compared to previous works. Finally, the calibrated DMISPE method was used for extraction and cleanup of sesquiterpene coumarins from asafetida plant. The concentration of isosamarcandin, kellerin and farnesiferol in asafoetida extract was obtained 0.8, 2.7, and 5 µg/mL, respectively, using standard addition method.

Simple and selective analysis of different antibiotics in milk using molecularly imprinted polymers: a review.

The frequent, sometimes illegal, use of antibiotics for therapeutic and prophylactic purposes in dairy cattle management may cause residues in milk. Because of problems concerning bacterial resistance or allergies in consumers, monitoring of residues is required. In spite of the huge development of analytical instrumentation during recent years, sample preparation is still a bottleneck of the analytical process. In this regard, efforts have been directed towards improving selectivity during extraction and clean-up of samples. Compared to traditional sorbents, molecularly imprinted polymers (MIPs) are excellent materials to provide selectivity for sample pretreatment. This review presents the application of MIPs as effective sorbents for separation, clean-up, pre-concentration and analysis of different antibiotics in milk.

Mechanisms of 2,3,7,8-tetrachlorodibenzo-p-dioxin- induced cardiovascular toxicity: An overview.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant and its toxicity is mediated by the aryl hydrocarbon receptor (AHR). Mechanisms of TCDD cardiovascular toxicity consist of oxidative stress, growth factor modulation, and ionic current alteration. It is indicated that the rodent cardiovascular system is a target for TCDD cardiomyopathy. Here, our understanding of TCDD cardiovascular toxicity is reviewed.

Comparison of a Point-of-Care Glucometer and a Laboratory Autoanalyzer for Measurement of Blood Glucose Concentrations in Domestic Pigeons ( Columba livia domestica).

Biochemical analysis is necessary for diagnosis and monitoring of diseases in birds; however, the small volume of blood that can be safely obtained from small avian species often limits laboratory diagnostic testing. Consequently, a suitable methodology requiring only a small volume of blood must be used. This study was designed to compare blood glucose concentrations in domestic pigeons ( Columba livia domestica) as measured by a commercial, handheld, human glucometer and a standard autoanalyzer. During the first phase of the study, whole blood samples obtained from 30 domestic pigeons were used to measure the blood glucose concentration with a glucometer, the packed cell volume (PCV), and the total erythrocyte count (nRBC). Plasma separated from the each sample was then used to obtain the plasma glucose concentration with the autoanalyzer. During the second phase of the study, 30 pigeons were assigned to 2 equal groups (n = 15). Hypoglycemia or hyperglycemia was induced in each group by intravenous injection of insulin or glucose, respectively. Blood was collected and processed, and glucose concentrations, PCV, and nRBC were measured as previously described. Linear-regression models demonstrated a significant relationship between results measured by the glucometer and autoanalyzer results from normoglycemic (correlation coefficient [R] = 0.43, P = .02), hypoglycemic (R = 0.95; P < .001), and hyperglycemic (R = 0.81; P < .001) birds. The results of this study suggest that we can predict the real blood-glucose concentration of pigeons by using results obtained by a glucometer.