Exercise Attenuates Anabolic Steroids-Induced Anxiety via Hippocampal NPY and MC4 Receptor in Rats

The aim of our study was to evaluate the effects of chronic administration of nandrolone-decanoate (ND) or testosterone-enanthate (TE) in supraphysiological doses and a prolonged swimming protocol, alone and in combination with ND or TE, on anxiety-like behavior in rats. We investigated the immunohistochemical alterations of the hippocampal neuropeptide Y (NPY) and melanocortin 4 receptor (MC4R) neurons, as a possible underlying mechanism in a modulation of anxiety-like behavior in rats. Both applied anabolic androgenic steroids (AASs) induced anxiogenic effect accompanied with decreased serum and hippocampal NPY. The exercise-induced anxiolytic effect was associated with increased hippocampal NPY expression. ND and TE increased the number of MC4R, while the swimming protocol was followed by the reduction of MC4R in the CA1 region of the hippocampus. However, NPY/MC4R ratio in hippocampus was lowered by AASs and elevated by exercise in all hippocampal regions. An augmentation of this ratio strongly and positively correlated to increased time in open arms of elevated plus maze, in the context that indicates anxiolytic effect. Our findings support the conclusion that alterations in both hippocampal NPY and MC4R expression are involved in anxiety level changes in rats, while their quantitative relationship (NPY/MC4R ratio) is even more valuable in the estimation of anxiety regulation than individual alterations for both NPY and MC4R expression in the hippocampus

The Impact of Hippocampal Sex Hormones Receptors in Modulation of Depressive-Like Behavior Following Chronic Anabolic Androgenic Steroids and Exercise Protocols in Rats

The aim of this study was to evaluate alterations in depressive-like behaviors in rats following chronic administration of a supraphysiological dose of anabolic androgenic steroids (AASs) as well as exposure to a prolonged exercise protocol. The role of hippocampal sex hormones receptors in the modulation of depressive-like behavior was also assessed. A total of 48 male Wistar albino rats were divided into six groups: control, exercise (1 h/day, five consecutive days), nandrolone-decanoate (ND, 20 mg/kg/week, in a single dose), exercise plus ND, testosterone-enanthate (TE, 20 mg/kg/week, in a single dose), and exercise plus TE. After the 6-week protocols were complete, the rats underwent behavioral testing in the tail suspension test (TST). Rats were sacrificed for the collection of blood samples, to determine sex hormones levels, and isolation of the hippocampus, to determine [androgen receptors (AR) and estrogen receptors α (ERα)] expression. ND and TE treatment induced significant depressive-like behavior, opposing the antidepressant effect of exercise. Chronic TE administration elevated testosterone (T) and dihydrotestosterone (DHT) serum levels, and this was augmented by exercise. In contrast, ND and exercise alone did not alter T or DHT levels. There were no changes in serum estradiol levels in any of the groups. Immunohistochemical analysis showed that exercise reduced AR immunoreactivity in all hippocampal regions and increased the ERα expression in the CA1, dentate gyrus (DG), and total hippocampal sections, but not in the CA2/3 region. AASs administration increased AR expression in all hippocampal regions, although not the total hippocampal section in the TE group and did not significantly decrease ERα. The hippocampal AR/ERα expression index was lowered while parvalbumin (PV)-immunoreactivity was enhanced by exercise. AASs administration increased the AR/ERα index and reduced PV-immunoreactivity in the hippocampus. The number of PV-immunoreactive neurons negatively correlated with the antidepressant effects and the AR/ERα ratio. Our results suggest a potential role of the numerical relationship between two sex hormones receptors (stronger correlation than for each individual receptor) in the regulation of depressive-like behavior via the hippocampal GABAergic system in rats, which allow better understanding of the hippocampal sex hormones receptors role in modulation of depressive-like behavior

The Investigation of the Chemical Composition and Applicability of Gold Nanoparticles Synthesized with Amygdalus communis (Almond) Leaf Aqueous Extract as Antimicrobial and Anticancer Agents

The current work’s main objective was to determine the chemical composition of Amygdalus communis (AC) leaf extract and examine the antibacterial and cytotoxic properties of biosynthesized gold nanoparticles (AuNPs). The chemical composition of AC leaf extract was determined using LC-ESI/MS/MS to detect compounds that may be responsible for the reducing, stabilizing, and capping steps in the synthesis of nanoparticles and their biological activities. The AC-AuNPs were spherical, with a particle size lower than 100 nm and a face-centered cubic structure. The EDX spectrum confirmed the formation of AuNPs and a negative zeta potential value (−27.7 mV) suggested their physicochemical stability. The in vitro cytotoxic efficacy of the AC-AuNPs against colorectal adenocarcinoma (Caco-2), glioma (U118), and ovarian (Skov-3) cancer cell lines and human dermal fibroblasts (HDFs) was evaluated by MTT assay. CaCo-2 cell proliferation was effectively inhibited by the AC-AuNPs at concentrations between 25 and 100 g mL−1. The AC-AuNPs exerted preeminent antimicrobial activity against Bacillus subtilis with an MIC of 0.02 μg/mL, whilst good activity was shown against Staphylococcus aureus bacteria and Candida albicans yeast with an MIC of 0.12 μg/mL. Ultimately, the results support the high antibacterial and anticancer potential of biosynthesized AuNPs from AC leaf extract

Behavioural effects of short-term total food restriction in rats

© 2014 University of Kragujevac, Faculty of Science. All rights reserved. Reducing food intake can decrease anxiety indices in rats. The aim of this study was to evaluate the influence of short-term (48 hours) total food restriction on the behavioural characteristics, the motor coordination and balance, of rats. Th ree-month-old male Wistar albino rats (n=20) weighing 350-400 g were divided into a control group (food and water intake ad libitum) and an experimental group (total food restriction 48 hours before testing). Behavioural studies were performed using the open field, elevated plus maze, Barnes maze, beam walking, evoked beam walking and linear locomotor tests. The total distance moved, the velocity, the movement and the frequency in the centre zone of the open field were significantly higher in the treated group. The cumulative duration in the centre zone of the open field did not significantly increase in the treated group. The number of entries into the open arms, the total time spent in the open arms and the total distance moved in the elevated plus maze significantly increased with no change in the velocity in the food-restricted animals. The 48 hours of total food restriction did not aff ect the Barnes maze test parameters or the parameters of the linear locomotor test. The velocity recorded during the beam walking test was not aff ected by the food restriction, but the velocity recorded during the evoked beam walking test significantly decreased in the treated group. In summary, short-term total food restriction did not produce significant changes in the physical performance of rats but did result in anxiolytic- like behaviour accompanied by food-seeking behaviour due to enhanced motivation to forage for food

Behavioural Effects of Short-term Total Food Restriction in Rats

Redukcija unosa hrane može dovesti do smanjenja anksioznosti kod pacova. Cilj ovog istraživanja je bio da se ispita uticaj kratkotrajnog (48 h), potpunog prekida unosa hrane na ponašanje, kao i motoričku koordinaciju i ravnotežu kod pacova. Tri meseca stari, muški Wistar albino pacovi (n=20), težine 350-400 g su podeljeni u kontrolnu grupu (unos hrane i vode ad libitum) i eksperimentalnu grupu - potpuni prekid unosa hrane 48 h pre testiranja. Bihejvioralna istraživanja su sprovedena uz korišćenje testova: „otvorenog polja”, „uzdignutog krstastog lavirinta”, Barnsovog lavirinta, „hodanja po gredi”, „izazvanog hodanja po gredi “ i linearnog lokomotornog testa. Ukupno pređeno rastojanje, brzina, kretanje i frekvencija ulazaka u centralnu zonu „otvorenog polja” su bili značajno veći u tretiranoj grupi. Ukupno vreme provedeno u centralnoj zoni „otvorenog polja” se nije značajno povećalo u tretiranoj grupi. Broj ulazaka u otvorene krake, ukupno vreme provedeno u otvorenim kracima i ukupno pređeno rastojanje u „uzdignutom krstastom lavirintu” su bili značajno povećani, dok se brzina nije menjala kod životinja bez unosa hrane. 48 h potpunog prekida unosa hrane nije imalo uticaja na parametre testa Barnsovog lavirinta, kao ni na parametre linearnog lokomotornog testa. Brzina registrovana kod testa „hodanja po gredi” se nije menjala usled restrikcije unosa hrane, ali se brzina registrovana kod testa „ izazvanog hodanja po gredi” značajno smanjila u grupi tretiranih životinja. Sumarno, kratkotrajni potpuni prekid unosa hrane nije izazvao značajne promene fi zičke sposobnosti pacova, ali je na ponašanje ispoljio efekte koji podsećaju na anksiolitičko dejstvo, uz obrasce koji podsećaju na traženje hrane usled povećane motivacije da se obezbedi hran

Antioxidant supplementation in the treatment of neurotoxicity induced by platinum-based chemotherapeutics—a review

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Cancer represents one of the most pernicious public health problems with a high mortality rate among patients worldwide. Chemotherapy is one of the major therapeutic approaches for the treatment of various malignancies. Platinum-based drugs (cisplatin, oxaliplatin, carboplatin, etc.) are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity. Simultaneously, researchers have tried to improve the survival rate and quality of life of cancer patients and decrease the toxicity of platinum-containing drugs by combining them with non-chemotherapy-based drugs, dietary supplements and/or antioxidants. Additionally, recent studies have shown that the root cause for the many side effects of platinum chemotherapeutics involves the production of reactive oxygen species (ROS) in naive cells. Therefore, suppression of ROS generation and their inactivation with antioxidants represents an appropriate approach for platinum drug-induced toxicities. The aim of this paper is to present an updated review of the protective effects of different antioxidant agents (vitamins, dietary antioxidants and supplements, medicaments, medicinal plants and their bioactive compounds) against the neurotoxicity induced by platinum-based chemotherapeutics. This review highlights the high potential of plant antioxidants as adjuvant strategies in chemotherapy with platinum drugs

An Overview of the Beneficial Role of Antioxidants in the Treatment of Nanoparticle-Induced Toxicities

Nanoparticles (NPs) are used in many products and materials for humans such as electronics, in medicine for drug delivery, as biosensors, in biotechnology, and in agriculture, as ingredients in cosmetics and food supplements. Besides that, NPs may display potentially hazardous properties on human health and the environment as a consequence of their abundant use in life nowadays. Hence, there is increased interest of researchers to provide possible therapeutic agents or dietary supplements for the amelioration of NP-induced toxicity. This review summarizes the new findings in the research of the use of antioxidants as supplements for the prevention and alleviation of harmful effects caused by exposure of organisms to NPs. Also, mechanisms involved in the formation of NP-induced oxidative stress and protective mechanisms using different antioxidant substances have also been elaborated. This review also highlights the potential of naturally occurring antioxidants for the enhancement of the antioxidant defense systems in the prevention and mitigation of organism damage caused by NP-induced oxidative stress. Based on the presented results of the most recent studies, it may be concluded that the role of antioxidants in the prevention and treatment of nanoparticle-induced toxicity is unimpeachable. This is particularly important in terms of oxidative stress suppression

The effects of N-acetylcysteine on cisplatin-induced cardiotoxicity on isolated rat hearts after short-term global ischemia

The aim of this study was to estimate the protective effect of N-acetyl-l-cysteine (NAC) against cisplatin-induced cardiotoxicity under conditions of ischemic-reperfusion injury. Wistar albino rats were randomly divided into three groups (n = 8): control, cisplatin (5 mg/kg/w, i.p., 5 weeks) and cisplatin + NAC group (cisplatin – 5 mg/kg/w, i.p. and NAC – 500 mg/kg/w, i.p., 5 weeks). Isolated hearts were perfused according to the modified Langendorff technique at constant pressure (70 cmH2O). Following cardiodynamic parameters were measured: maximum rate of left ventricular pressure development, minimum rate of left ventricular pressure development, left ventricular systolic pressure (SLVP), left ventricular diastolic pressure and heart rate. The ischemic vasodilation episodes were induced by the complete interruption of coronary inflow for 30, 60 and 120 s. The samples of the coronary venous effluent (CVE) were continuously collected during the reperfusion period for determination of coronary flow (CF) rate and oxidative stress markers (H2O2, O2−, NO2− and thiobarbituric acid reactive substances – TBARS). Cisplatin reduced CF, heart rate and overflow (total, maximal and duration of overflow) during reperfusion, and increased SLVP (under basal conditions and after global ischemias). Cisplatin increased levels of H2O2 (under basal conditions), O2− and TBARS (under basal conditions and after ischemia), but decreased NO2− levels (during reperfusion) in CVE, and decreased superoxide dismutase and reduced glutathione in serum. NAC attenuated cisplatin-induced changes of cardiodynamic parameters (except CF under basal conditions) and oxidative stress parameters. Those results suggest that NAC, by decreasing oxidative stress, may be useful in cardioprotection during cisplatin therapy

The Effects of Methionine-Enriched and Vitamins (Folate, Pyridoxine and Cobalamine)-Deficient Diet on Exploratory Activity in Rats - A Brief Report

The aim of this study was to evaluate the impact of increased homocysteine levels induced by methionine nutritional overload (twice as standard) and deficiency of the vitamins folate, pyridoxine and cobalamine, which plays an important role in homocysteine metabolism in anxiety-related behaviour, expressed by means of exploratory activity in rats. Twenty-three male Wistar albino rats (4 weeks old, 100±15 g body weight) were divided into three groups: control (n=8), methionine-enriched (Meth+, 7.7 g of methionine/kg chow, n=7) and methionine-enriched vitamin-deficient (Meth+Vit-, 7.7 g of methionine/ kg chow, deficient in folate, pyridoxine and cobalamine - 0.08, 0.01 and 0.01 mg/kg, n=8). All animals had free access to food and water for 30 days. Behavioural testing was performed using the elevated plus maze (EPM) test. Standard parameters for vertical exploratory activity, the number of rearings and the number of head-dippings, as well as the total exploratory activity (summarizing overall exploratory activity in the EPM) were significantly reduced following 30 days of methionine nutritional overload (p<0.05, p<0.05 and p<0.01, respectively). A methionine-enriched diet coupled with a reduction in some B vitamins resulted in a more pronounced decline in exploratory drive observed in the EPM test compared to the control (p<0.01). The decline in total exploratory activity associated with vitamin deficiency was significant compared to the Meth+ group (p<0.05). The results of this study highlight the important role of homocysteine in the modulation of exploratory activity in rats. Decreased exploratory drive induced by both a methionine-enriched and vitamin-deficient diet could be attributed to an anxiogenic effect of hyperhomocysteinemia