Effects of treatment with haloperidol and clozapine on the plasma concentrations of thyroid hormones in rats

Publisher's version (útgefin grein)Objectives. Psychoactive drugs are group of compounds used to treat severe mental problems, including psychosis, as well as other conditions. This study assessed clinically relevant side effects of haloperidol and clozapine on the thyroid hormones. Methods. Haloperidol (0.05 and 2 mg/kg) or clozapine (0.5 and 20 mg/kg) was intraperitoneally injected to male Wistar rats for 28 days. The control group received 2 ml of physiological saline. A chemiluminescent immunoassay was used to measure the plasma levels of thyroid hormones. Results. Plasma concentrations of thyroxine (T4) in rats treated with high-dose (2 mg/kg) of haloperidol decreased significantly compared to the control group (p=0.001). However, both low (0.5 mg/kg) and high clozapine (20 mg/kg) doses did not have a significant effect on the plasma concentrations of T4 and triiodothyronine (T3) (p>0.05). Neither of the compound had a significant effect on T3 plasma concentration levels (p>0.05). Conclusions. Haloperidol and clozapine act via different mechanisms and may have dissociable effects on thyroid hormones. Following treatment with haloperidol, significant changes in T4, but not in T3, serum levels were observed. Haloperidol and clozapine had different effects on the thyroid hormone levels. These results indicate that antipsychotic treatment can contribute to the thyroid dysfunction. Therefore, greater caution should be applied to the antipsychotics use. The thyroid function of the patients should be closely monitored, while using these drugs.This study was supported by the vice president of research of Urmia University of Medical Sciences.Peer Reviewe

Curious Cases of the Enzymes / Neobiča Istorija Enzima

: Život oko nas uglavnom se zasniva na biološkoj katalizi, pa bi se čak, u nekakvoj neromantičnoj priči, život mogao opisati kao niz hemijskih reakcija koje regulišu glavni principi termodinamike. U davnoj prošlosti, ku­canje srca bilo je znak dobrog zdravlja, međutim, za mene, najvažniju ulogu ima upravo prisustvo enzima... Mada ne obraćamo često pažnju na to, istorija enzimologije stara je koliko i sam ljudski rod i seže daleko u prošlost. CVaj rad posvećen je baš tim počecima u ovoj veoma zanimljivoj nauci, koja je u prošlosti ostavila traga na našim životima i koja će u budućnosti učiniti da život bude mnogo pro­duktivniji za čovečanstvo. Između čoveka i enzima postojao je oduvek jedan delikatan, suštinski važan odnos. Suočen s nepoznatom i neprijateljski nastrojenom prirodom punom grabljivaca, preistorijski čovek rano je otkrio lekovita svojstva biljaka, i to metodom probe i greške. Štaviše, slučajno su otkriveni inhibitori enzima, čime je, grubo rečeno, još tada otvorena nova oblast istraživanja. Oi biljni derivati koji su imali ulogu inhibitora enzima pomagali su preistorijskom čoveku u njegovoj borbi da opstane i zaštiti se od grabljiva­ca; prilikom lova i ribolova... Kasnije kroz istoriju, sa nepro- menjenom svrhom opstanka i poboljšanja kvaliteta života, enzimologija je iz korena transformisana, a metodologiju »probe i greške« iz praistorije zamenile su racionalne naučne teorije

Effects of the in-utero dicyclohexyl phthalate and di-n-hexyl phthalate administration on the oxidative stress-induced histopathological changes in the rat liver tissue correlated with serum biochemistry and hematological parameters

Phthalates are widely used as plasticizers in the industry and are found in cosmetics, food and drink packaging, drugs, toys, households, medical devices, pesticides, personal care products, and paints. Phthalates exert endocrine disrupting and peroxisome proliferator effects in humans and wildlife associated with the pathogenesis of various diseases, including diabetes, obesity, infertility, cardiovascular diseases, metabolic syndrome, and cancer. Since phthalates are metabolized in the liver, which regulates the body’s energy metabolism, long or short-term exposure to the phthalates is associated with impaired glucose, lipid, and oxidative stress metabolisms contributing to liver toxicity. However, the impact of in-utero exposure to DHP and DCHP on liver metabolism has not been studied previously. Thus, in this study, we evaluated serum biochemistry parameters, hematological markers, histopathological changes, and oxidative and pentose phosphate pathway (PPP) metabolisms in the liver following in-utero DHP and DCHP administration, respectively, in male and female rats. We found increased relative and absolute liver weights and impaired triglyceride, alanine transaminase (ALT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels upon dicyclohexyl phthalate (DCHP) and di-n-hexyl phthalate (DHP). Histopathological changes, including congestion, sinusoidal dilatation, inflammatory cell infiltration, cells with a pyknotic nucleus, lysis of hepatocytes, and degeneration of hepatic parenchyma have been observed in the liver samples of DHP and DCHP dose groups. Moreover, increased glutathione s-transferase (GST), glucose 6-phosphate dehydrogenase (G6PD), and glutathione reductase (GR) activities have been found in the liver samples of DHP and DCHP-treated rats associated with impaired pentose phosphate pathway (PPP) and oxidative stress metabolism. First time in the literature, we showed that in-utero exposure to DHP and DCHP causes liver damage associated with impaired oxidative stress metabolism in male and female rats. Our data may guide researchers and governments to regulate and restrict phthalates in industrial products

In vitro effects of compounds isolated from Sideritis brevibracteata on bovine kidney cortex glutathione reductase

Glutathione reductase (GR, E.C 1.6.4.2) is a flavoprotein that catalyzes NADPH-dependent reduction of oxidized glutathione (GSSG) to reduced glutathione (GSH). The aim of this study was to investigate in vitro effects of phenolic compounds isolated from Sideritis brevibracteata on bovine kidney GR. The Sideritis species are widely found in nature and commonly used as medicinal plants. 7-O-glycosides of 8-OH-flavones (hypolaetin, isoscutellarein and 3'-hydroxy-4'-O-methylisoscutellarein) were isolated from aerial parts of Sideritis brevibracteata. These compounds inhibited bovine kidney cortex GR in a concentration-dependent manner. Kinetic characterization of the inhibition was also performed

Synthesis and characterization of a triple enzyme-inorganic hybrid nanoflower (TrpE@ihNF) as a combination of three pancreatic digestive enzymes amylase, protease and lipase

Nanoflowers are recently developed flower-shaped nanoparticles consisting of several layers of petals to improve surface reaction and stability. Among them organic-inorganic hybrid nanoflowers have been spotlighted, since they can overcome enzyme-related limitations, including low stability, high production cost, substrate/product inhibition and difficult recovery. In this study, triple enzyme-inorganic hybrid nanoflowers (TrpE@ihNFs) were synthesized using a mixture of three enzymes (alpha-amylase, lipase and protease) and Cu2+ ions. TrpE@ihNFs were characterized by their morphology and chemical point of view by using different techniques including SEM, FTIR, EDX, and XRD. Afterwards we compared the enzyme activity and stability of TrpE@ihNFs with the free enzymes, including lipase, amylase and protease at the different pH and temperatures spectrophotometrically. Our data reveal that enzyme activities and stability of TrpE@ihNFs were significantly higher compared to the each free enzyme. In conclusion, we showed TrpE@ihNFs which can be used for the treatment of wastewater, biosensors, biocatalysts, and bio-related devices in the future. (C) 2020, The Society for Biotechnology, Japan. All rights reserved

Effects Of Timolol Treatment On Pancreatic Antioxidant Enzymes In Streptozotocin-Induced Diabetic Rats: An Experimental And Computational Study

Background: The study aimed to investigate whether timolol-treatment has a beneficial effect on pentose phosphate pathway enzyme activities such as glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGDH) enzyme activities and cAMP level in streptozotocin-induced diabetic rats in pancreatic tissues Methods: Diabetes was induced by streptozotocin (STZ) in 3-month old male Wistar rats. The diabetic rats were treated with timolol (5 mg/kg body weight, for 12 weeks) while the control group received saline. Enzyme activities were determined in pancreas tissue. To support our results, we performed in silico calculations, using Protein Data Bank structures. Results: Timolol treatment of STZ-induced diabetic rats had no noteworthy effect on high blood-glucose levels. However, this treatment induced activities of G6PD and 6PGDH in diabetic rats. Timolol treatment significantly increased cAMP level in diabetic pancreatic tissue. We found that timolol cannot bind strongly to either G6PD or 6PGD, but there is a relatively higher binding affinity to adenylyl cyclase, responsible for cAMP production, serving as a regulatory signal via specific cAMP-binding proteins. Conclusions: Our data point out that timolol treatment has beneficial effects on the antioxidant defence mechanism enzymes in the pancreas of STZ-induced diabetic rats.WoSScopu

Evaluation of the Hematological and Serum Biochemistry Parameters in the Pre-Symptomatic and Symptomatic Stages of ALS Disease to Support Early Diagnosis and Prognosis

Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease. Since there are no pathognomonic tests for ALS prognoses; clinical diagnoses of the disease take time and are usually difficult. Prognostic biomarkers are urgently needed for rapid and effective ALS prognoses. Male albino rats were divided into ten groups based on age: 0 (40–45 days old), A (70–75 days old), B (90–95 days old), C (110–115 days old), and D (130–135 days old). Each group was divided into two subgroups according to its mutation status: wild type (SOD1WT) or mutated (SOD1G93A). Serum biochemistry and hematological parameters were measured in 90 rats to evaluate possible biomarkers for faster ALS diagnoses and prognoses. Weight loss, cholesterol, creatinine, glucose, total bilirubin (TBIL), blood urine nitrogen (BUN), c-peptide, glucagon, PYY, white blood cell (WBC), lymphocyte (LYM), monocyte (MID), granulocyte (GRAN), red cell distribution width with standard deviation (RDW-SD), red cell distribution width with the coefficient of variation (RDW-CV), platelet (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and procalcitonin (PCT) levels were changed in the SOD1G93A rats compared to the SOD1WT rats independently from aging. For the first time in the literature, we showed promising hematological and serum biochemistry parameters in the pre-symptomatic and symptomatic stages of ALS by eliminating the effects of aging. Our results can be used for early diagnoses and prognoses of ALS, improving the quality of life and survival time of ALS patients

Comparison Of Spectrophotometric And Fluorimetric Methods In Evaluation Of Biotinidase Deficiency

Background Biotin, a water-soluble vitamin, is used as a co-factor by enzymes involved in carboxylation reactions. Biotinidase (BTD) catalyzes the recycling of biotin from endogenous and dietary sources. Biotinidase deficiency (BD) is an autosomal recessively inherited disorder of biotin recycling that is associated with neurologic and cutaneous consequences when untreated. The aim of the study was to compare the results of spectrophotometric and fluorimetric methods, as well as to evaluate the advantages and disadvantages of both methods in current research practices. Methods Study group was chosen among the BD suspected newborn, children and parents (n = 52) who applied to Hacettepe University Pediatric Metabolism Unit. Results BTD activity is stable for 2 hours at room temperature and at 4 °C, and for 4 months at –20 °C and –80 °C. Genetic and clinical results showed that 25% of the total number of patients had complete BD which was treated with 10 mg/day biotin, while 15.38% of the patients had partial BD, and they were prescribed biotin 5 mg/day. The area under the ROC curve was 0.960±0.25 and 0.927± 0.41 for the fluorimetric and spectrophotometric method, respectively. Fluorimetric method showed 100% sensitivity and 97% specificity, whereas spectrophotometric method showed 90.5% sensitivity and 93.7% specificity. Conclusions Fluorimetric method is superior to the spectrophotometric method due to higher sensitivity and specificity.PubMedWoSScopu