Band 29, Heft 1

Background: Caffeine antagonizes the intoxicating effects of alcohol. Consequently, there has been a dramatic global increase in the consumption of caffeinated drinks together with alcohol, especially among young adults. We assessed the seizure vulnerability and anxiety responses following the chronic co-administration of, and withdrawal from, caffeine and ethanol in male rats. Methods: The rats were randomly assigned to six groups consisting of 10 animals each: 10 mg/kg of caffeine, 20 mg/kg of caffeine, 4 g/kg of 20% ethanol, combined caffeine (20 mg/kg) and ethanol (4 g/kg of 20%), 4 mL/kg distilled water, and an untreated control group. The test substances were administered intragastrically twice daily for 29 days. On day 29, the rats were tested on the elevated plus maze to assess anxiety-related responses. On day 30, pentylenetetrazol (PTZ), a chemoconvulsant, was administered intraperitoneally at a dose of 40 mg/kg to the animals. Seizure responses and mortality up to 72 h were recorded. Results: Compared with the control group, the rats that received chronic treatment with low-dose caffeine, ethanol alone, and combined caffeine and ethanol exhibited significant anxiogenic-like effects, unlike with high-dose caffeine. Both low- and high-dose caffeine significantly increased PTZ seizure latency. Ethanol alone and combined caffeine and ethanol both lowered PTZ seizure latency. No significant difference occurred between the controls and the untreated group for either anxiety or seizure expression. Combined caffeine and ethanol increased the seizure-induced mortality from withdrawal effects at 72 h. Conclusions: These findings suggest that the chronic co-administration of caffeine and ethanol and the acute withdrawal from these drugs lead to anxiogenic effects and increased seizure vulnerability.

Background: Anemia aggravates the disease course and the survival rate of chronic heart failure (CHF) patients. The purpose of the study was to investigate the level of erythropoietin (EPO) in CHF patients with anemic syndrome, with the aim to more accurately assess the severity of the disease and its treatment, depending on the anemia degree. Methods: Patients with ischemic CHF of I–IV functional class (FC) with and without anemia were examined (total number of patients=208, patients with anemia=174). The EPO was determined using the enzyme-linked immunosorbent assay. Before treatment, the patients underwent the following medical therapy: angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, long-acting nitrates, diuretics, digoxin, and beta-blockers at individual doses. Depending on the plasma EPO level, the CHF patients with anemia were divided into four randomized groups in terms of treatment. Results: Normal erythropoietinemia was found in 36.2% of the CHF patients with anemic syndrome (I–III FC), hypoerythropoietinemia in 44.8% (III–IV FC), and hypererythropoietinemia in 18.96% (III–V FC). The EPO level in the blood plasma of the patients with I–II FC CHF with hypoerythropoietinemia, who were treated with methoxy polyethylene glycol-epoetin β (MEB), increased by 2.2 times. Combination therapy with disease-modifying drugs and MEB led to a significant increase in the plasma EPO level in the CHF patients with hypoerythropoietinemia. Conclusions: It was shown that the EPO level in patients with CHF and anemia did not always drop. Hypererythropoietinemia in patients with CHF and anemia leads to an unfavorable treatment prediction. This necessitates the investigation of the EPO level in all patients with CHF before and after treatment, with the aim of correcting the anemic syndrome. The research showed that the combined therapy of patients with CHF and anemia using MEB medication and iron with regard to the EPO level in the blood plasma improved their overall physical condition, reduced heart failure symptoms and hospitalization frequency, and demonstrated a clear tendency to reduce the general mortality rate.

Background: The use of doxorubicin (DOX) as an antineoplastic agent has been greatly limited because of the myriad of toxic sequelae associated with it. The aim of this study was to assess the protective effects of gallic acid (GA) on DOX-induced cardiac toxicity in rats. Methods: Sixty male rats (Wistar strain) were used in this study. They were divided into six groups (A–F) each containing 10 animals. Group A was the control. Rats in Groups B, C, and D were treated with DOX at the dosage of 15 mg/kg body weight i.p. Prior to this treatment, rats in Groups C and D had been treated orally with GA for 7 days at the dosage of 60 and 120 mg/kg, respectively. Animals from Groups E and F received only 60 and 120 mg/kg GA, respectively, which were administered orally for 7 days. Results: The exposure of rats to DOX led to a significant (p<0.05) decrease in the cardiac antioxidant defence system and elevation of creatine kinase myocardial band and lactate dehydrogenase. The electrocardiography results showed a significant decrease in heart rate, QRS, and QT-segment prolongation. GA alone improved the antioxidant defence system. Conclusions: The GA pretreatment significantly alleviated GA-associated ECG abnormalities, restored the antioxidant status and prevented cardiac damage.

Background: Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl 4 ). Methods: CCl 4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl 4 -treated rats. Results: CCl 4 significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl 4 -induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05). Conclusions: The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl 4 -induced hepatotoxicity.

Background: Tamarindus is a monotypic genus and belongs to the subfamily Caesalpinioideae of the family Leguminosae (Fabaceae), Tamarindus indica L., commonly known as Tamarind tree is one of the most important multipurpose tropical fruit tree species in the India, Sudan, Nigeria, Bangladesh and entire subcontinent. Methods: Hydroethanolic seed coat extract of Tamarindus indica (HETI) was assessed for presence of phytoconstituents and selection of optimum dose through acute and sub acute toxicity study. The single and multidose (14 days) study were conducted to evaluate antidiabetic potential of HETI in alloxan induced rats via determine of blood glucose level, body weight, hematological profile, extra-pancreatic glucose utilization of isolated rat hemi-diaphragm as well as histopathology of rat pancreas. Results: Phytochemical analysis of HETI showed the presence of polyphenol like flavonoids. Single and multidose of HETI significantly (p<0.05; p<0.001) reduced blood glucose level in normoglycaemic, glucose loaded and alloxan induced hyperglycaemic animals. HETI exerts the protective effect on pancreatic β-cells as per results obtained from histopathology of animals. Moreover, HETI increased glucose uptake in isolated rat hemi-diaphragm and prevents decrease in body weight along with recovery of altered hematological parameters. Conclusions: The study revealed that HETI have potent hypoglycaemic action by virtue of its phytoconstituents and it can be used as a herbal medicine for diabetes.

Background: Patients with diabetes mellitus (DM) are at risk of experiencing chronic complications such as retinopathy, nephropathy and myopathy. We aimed to evaluate the effects of L-carnitine on type II DM (T2DM)-induced biochemical, contractile and pathological changes in skeletal muscles of rats. Methods: Thirty-two male Sprague Dawley rats were divided into the control, control+L-carnitine, T2DM and T2DM+L-carnitine groups. Plasma levels of glucose, insulin, malondialdehyde and antioxidants such as reduced glutathione, catalase and superoxide dismutase, haemoglobin A1c (HbA1c), insulin sensitivity index (ISI) as well as the contractile properties of the gastrocnemius muscle were measured. Also, histopathological studies and immunohistochemical examination of the gastrocnemius muscle using the MuRF1 (muscle RING-finger protein-1) marker were performed. Results: In diabetic rats, malondialdehyde, glucose, insulin, HbA1c and MuRF1 were increased, whereas ISI and antioxidants were decreased and the contractile properties deteriorated. L-carnitine decreased malondialdehyde, glucose, insulin, HbA1c and MuRF1 and increased ISI and antioxidants. Also, L-carnitine improves the contractile properties in diabetic rats. Histopathological studies confirm our data. Conclusions: We conclude that L-carnitine exhibits protective effects on skeletal muscles of T2DM rats through its hypoglycemic and antioxidant actions as well as its inhibitory effect on protein degradation.

Background: Nonalcoholic fatty liver disease (NAFLD) is associated with a systemic procoagulant hypofibrinolysis state that is considered as a risk factor for microangiopathy and peripheral vascular diseases. Swimming exercise ameliorates the metabolic dysfunction in type 2 diabetes. Vitamin E is a natural antioxidant that reduces the risk of endothelial dysfunction in metabolic syndrome. The aim of the present study is to investigate the effect of combined swimming exercise with vitamin E on coagulation as well as blood fibrinolysis markers in rats with NAFLD. Methods: Eighty male rats were divided into control, control+vitamin E, control+exercise, high-fat diet (HFD), HFD+vitamin E, HFD+exercise, and HFD+vitamin E+exercise groups. Glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides, cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alanine transaminase (ALT) and aspartate transaminase (AST), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1, von Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), platelet count and aggregation, bleeding and clotting times, activated partial thromboplastin time (aPTT), and prothrombin time (PT) were determined. Results: HFD increased lipid profile, insulin, glucose, HOMA-IR, liver enzymes, adhesion molecules, endothelin-1, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1, and decreased clotting and bleeding times and HDL. Although exercise reduced lipid profile, glucose, insulin, HOMA-IR, vWF, platelet aggregation, fibrinogen, FDP, and PAI-1 and increased PT, aPTT, bleeding and clotting times, and HDL, vitamin E had no effect. Conclusions: Exercise, but not vitamin E, ameliorated the HFD-induced prothrombotic state and enhanced fibrinolytic activity.

Background: Curcumin and nisin have been widely reported for their antibacterial and anticancer potency. However, their therapeutic applications are hampered by several factors, which necessitate their development into nanosize ranges for improved delivery and activities. Their incorporation into a single nanosynthesized form may suggest desirable efficacy on parasites. The aim of the study was to assess the ovicidal activity of the curcumin-nisin polylactic acid (PLA) entrapped nanoparticle on the Fasciola eggs and its reproductive toxicity. Methods: The nanoparticle was formulated by double emulsion method. The eggs of the adult Fasciola spp. were exposed to different concentrations (0.3125–5 mg/mL) of the nanoparticle to monitor hatchability. Mice were exposed to 0.5 mL of the formulated drug at varying concentrations (10–20 mg/kg) and then sacrificed for sperm morphology assay. Results: The mean particle size, polydispersity index, and drug entrapment efficiency of the formulated drug were 288.4±24.3 nm, 0.232, and 51.7%, respectively. The highest nanoparticulate concentration (5 mg/mL) showed the least percentage egg hatching (41.7%) compared with the other treatment groups and positive control (albendazole) (45.1%). The aberrations observed in sperm cells were not concentration-dependent and no significant differences were observed in the mean aberrations between the nanoparticulate drug-exposed groups and the negative control (p>0.05). Conclusions: The results confirmed the ovicidal activity of the curcumin-nisin nanoparticulate drug against the Fasciola species. The formulation also showed no toxicity to sperm cells. More robust studies on anti-fascioliasis activity of the drug on adult Fasciola spp. and in vivo and in vitro toxicity studies are recommended.

Background: The plant under investigation ( Tetracera sarmentosa ) is a dicotyledonous flowering plant and belongs to the family Dilleniaceae. The goal of our investigation was to determine whether the leaf extracts of this plant held any significant medicinal properties. Methods: Leaves of T. sarmentosa were extracted with pure ethanol (EETS) and methanol (METS), and then methanol extract fractioned with n -hexane (NHFMETS) and chloroform (CHFMETS). The extracts and fractions were tested for antioxidant activity, which was measured by using qualitative and quantitative procedures. Thrombolytic activity was evaluated by the clot lysis test. Analgesic activity was evaluated employing the acidic acid-induced writhing test, the formalin-induced paw licking test and tail immersion on Swiss albino mice. The anti-inflammatory activity test was studied using the paw edema test. Forced swimming, tail suspension, elevated plus maze and hole board model tests were used to evaluate neuropharmacological activity. Results: All the extracts and fractions possessed antioxidant effects. All the extracts, fractions and streptokinase exhibited significant (p<0.0001) clot lysis. The extracts and fractions produced significant analgesic effects as evaluated by the acetic acid writhing test, the formalin-induced paw licking test and the tail immersion method. Similarly, carrageenan-induced inflammation was significantly antagonized by the treatments. The extracts and fractions also significantly showed neuropharmacological (antidepressant and anxiolytic) effects. Conclusions: The overall results suggested that this plant deserves further investigation to isolate the active compounds which are responsible for these activities and to establish the mechanism of action.

Background: Currently, mushrooms have been used in traditional and folk medicines for their therapeutic activities, such as antibiotic, antitumor, anti-inflammatory, anticancer, antileukemic and immunomodulatory actions. This investigation evaluates the anti-invasive, antiproliferative and cytotoxic effects of Pleurotus ostreatus (Pleurotaceae) on leukemia cell lines. Methods: The proliferation of KG-1 cells was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with gradient dilutions of P. ostreatus extract. Then, the minimum inhibitory concentration (MIC) of the extract was determined. Moreover, the proliferation of Jurkat cells and bone marrow mesenchymal stem cells (BMSCs), a cancerous cell line and normal body cells, respectively, was considered. The apoptotic morphology of treated KG-1 cells was evaluated with Giemsa staining. The invasion and migration of cells were evaluated using transwell invasion assay. Thereafter, the rates of apoptosis and necrosis were measured by using flow cytometry, and BAX and MMP-9 gene expression were evaluated using quantitative reverse transcription-polymerase chain reaction as apoptotic and metastatic genes, respectively. Results: The MIC of the extract was determined to be 1 mg/mL after 48 h. According to the results, the extract decreased the proliferation of leukemia cell lines (KG-1 and Jurkat cells) but had no antiproliferative effects on BMSCs. Moreover, KG-1 cell migration and MMP-9 gene expression decreased after the treatment, and the rate of apoptosis and BAX gene expression increased significantly. Conclusions: According to the efficient therapeutic properties of P. ostreatus on leukemia cell lines, this mushroom could be introduced as a natural medicine to cure leukemic patients who suffer from the harmful side effects and enormous costs of chemotherapy.