Band 30, Heft 5

Cardioprotection is a very challenging area in the field of cardiovascular sciences. Myocardial damage accounts for nearly 50% of injury due to reperfusion, yet there is no effective strategy to prevent this to reduce the burden of heart failure. During last couple of decades, by combining genetic and bimolecular studies, many new drugs have been developed to treat hypertension, heart failure, and cancer. The use of percutaneous coronary intervention has reduced the mortality and morbidity of acute coronary syndrome dramatically. However, there is no standard therapy available that can mitigate cardiac reperfusion injury, which contributes to up to half of myocardial infarcts. Literature shows that the activation of sphingosine receptors, which are G protein-coupled receptors, induces cardioprotection both in vitro and in vivo . The exact mechanism of this protection is not clear yet. In this review, we discuss the mechanism of ischemia reperfusion injury and the role of the FDA-approved sphingosine 1 phosphate drug fingolimod in cardioprotection.

Background The brain is the centre of the nervous system in all vertebrates. The central cholinergic pathways play a prominent role in learning and memory processes. Dementia is a mental disorder characterized by the loss of intellectual ability, which invariably involves the impairment of memory. The crude extracts of the Gmelina arborea plant are reported to possess wound-healing, anti-diarrheal, anti-oxidant, anti-diabetic, and anti-ulcer property. The present study was designed to evaluate the effects of G. arborea on learning and memory in albino Wistar rats. Methods A total of 36 healthy rats were selected for the study, which were divided in to six groups. Standard screening tests such as the elevated plus maze (EPM), Morris water maze (MWM), and step-down passive avoidance (SDA) tests were used for testing the learning and memory processes. Results Gmelina arborea at higher doses (1000 mg/kg) showed statistically significant activity in EPM, MWM, and SDA tests for assessing the learning and memory paradigms when compared to the control group in amnesia-induced and non-amnesia groups of rats. Conclusions This is the first ever study to report the effects of G. arborea on learning and memory in both amnesia-induced and non-amnesia groups of rats. Our results show that G. arborea potentiates the processes of learning and memory. The observed pharmacological activities should be further evaluated by detailed experimental studies and revalidated by clinical trials.

Background Caffeinated coffee, a psycho-stimulant, is widely consumed throughout the globe. However, its chronic consumption has deleterious effects on human health. Meanwhile, decaffeinated coffee has low content of caffeine and thus can be an alternative to caffeinated coffee. Therefore, the study was undertaken to explore and compare the acute effects of decaffeinated and caffeinated coffee on reaction time, mood and skeletal muscle strength in healthy volunteers. Methods This was a prospective, interventional, comparative type of study. The study included 70 healthy adults divided into two groups (Caffeinated coffee group and Decaffeinated coffee group). The following parameters were assessed: reaction time was assessed by digital display multiple-choice apparatus, mood by Visual Analogue Scale (VAS) and Profile of Mood States revised version (POMS) and skeletal muscle strength by hand dynamometer. All parameters in both groups were assessed pre-intervention (baseline) and 30 min post-intervention. Results In both groups (decaffeinated and caffeinated coffee) post-intervention, there was a statistically significant (p < 0.05) improvement in the reaction time (VRT) and mood (VAS, POMS) from the baseline. However, both groups did not show any significant effects on the skeletal muscle strength. Upon comparing the two groups, we found that caffeinated coffee showed higher and significant improvement of mood than decaffeinated coffee. Conclusions Decaffeinated coffee exerts an acute significant stimulatory effect on the reaction time and mood. However, these effects in comparison to caffeinated coffee are low. Further randomized control clinical trials are thus needed to validate these interesting findings.

Background Short-term memory impairment is a neurodegenerative disease associated with oxidative stress. Bryophyllum pinnatum (Lam.) Oken of the family Crassulaceae is traditionally used in the treatment of diseases, such as cough, wounds, and kidney diseases. This study evaluates the effect of the aqueous extract of B. pinnatum (AEBP) leaves on acetylcholinesterase activity in carbon tetrachloride (CCl 4 )-induced short-term memory impairment in rats. Methods Thirty male Wistar albino rats were used in this study and were divided into six groups (n=5). Group I served as control, group II rats were induced with CCl 4 , while groups III–V animals were pretreated with silymarin (25 mg/kg body weight), 25 and 50 mg/kg body weight AEBP leaves, respectively, once daily by oral gavage for 14 days prior to a single intraperitoneal injection of CCl 4 . Animals in group VI received 50 mg/kg body weight AEBP only by oral gavage. Results Administration of carbon tetrachloride significantly increased (p<0.05) spontaneous alternation and locomotor function in rats when compared with the control group. Also, the levels of acetylcholinesterase, adenosine deaminase, and malondialdehyde were increased in CCl 4 -administered rats, with reduction in both enzymatic and nonenzymatic antioxidant levels. However, pretreatment of rats with AEBP leaves, at tested doses, prevented these changes. Conclusions The increased antioxidant status and the inhibition of acetylcholinesterase activity show that AEBP leaves improve learning memory and stabilizes memory impairment caused by CCl 4 .

Background Diazinon (DZN) causes serious liver damage in both humans and animals. In the present study, the hepatoprotective effects of Cynara scolymus L. leaf extract against DZN-induced liver injury were examined. Methods Forty male rats were divided into five groups. The control group received a normal diet. The DZN group received DZN only (25 mg/kg, po ). The DZN + Syl group received DZN (25 mg/kg, po ) and silymarin (Syl) (50 mg/kg, po ). The DZN + Art group received DZN (25 mg/kg, po ) and artichoke (Art) leaf extract (1500 mg/kg, po ). The Art group received Art leaf extract only (1500 mg/kg, po ). After 15 days, serum tumor necrosis factor α (TNF-α), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid profile, protein carbonyl content, serum and hepatic malondialdehyde (MDA), hepatic TNF-α gene expression, hepatic catalase (CAT), superoxide dismutase (SOD), and vitamin C (Vit C) were measured and histopathological examination was performed. Results DZN caused a significant elevation in serum ALP, AST, ALT, MDA, TNF-α, protein carbonyl, hepatic MDA, and TNF-α gene expression in the DZN group as opposed to the control group. Also, DZN led to the reduction of hepatic CAT, SOD, and Vit C in the DZN group relative to the control group. The administration of Art extract resulted in not only a significant reduction in serum ALP, AST, ALT, MDA, TNF-α, and protein carbonyl but also an improvement of liver histopathological changes and hepatic CAT and SOD activities as opposed to the DZN group. Conclusions This study confirmed that Art leaf extract has liver protective effects and causes downregulation of oxidative stress in acute DZN-induced liver injury in rats.

Background In recent years, increased stress in human life has a dual effect on brain and body physiology. Chronic stress takes a toll on physiology as well as on quality of life, ultimately leading to affective disorders. Rodent models are indispensable tools for studying the etiology and progress of depression. C-reactive protein has been proposed as a novel inflammatory marker. Methods Rats were divided into control and experimental stress groups (n = 6 each). The experimental group consisted of rats that were exposed to a set of chronic unpredictable stressors for 15 days. At the end of the 15th day, the animals were anesthetized, and blood samples were collected through cardiac puncture. Then the blood samples were analyzed for selected biochemical and oxidative stress parameters. Results Serum glutamic oxaloacetic transaminase (p < 0.0001), serum glutamic pyruvic transaminase (p < 0.001), serum malondialdehyde (p < 0.0001), total antioxidant level (p < 0.0001), and serum cortisol (p < 0.0001) were significantly increased in the stressed group when compared with the control group. C-reactive protein significantly (p < 0.0001) increased in the stressed group when compared with the control group. Conclusion Our results demonstrate that chronic unpredictable stress ameliorated depression-like behavior, which might have caused the dysregulation of the hypothalamic-pituitary-adrenal axis, causing the imbalance in the biochemical and oxidative parameters increasing the inflammatory markers. The inflammation-induced model of the chronic unpredictable stress model of comorbid depression might provide a variety of new targets for antidepressant therapies.

Background Combined oral contraceptive (COC) use has been associated with an increased risk of insulin resistance (IR) and other adverse cardiovascular events, despite efforts to reduce the dosage and/or progestin type. COC containing drospirenone (DRSP) is an analog of spironolactone, hence its antimineralocorticoid and antiandrogenic characteristics have been deemed beneficial, although the benefits and/or negative outcome of its usage have not been fully elucidated. We therefore hypothesized that COC with DRSP component will not affect glucose regulation and circulating corticosterone. Method Ten-week-old female Wistar rats were divided into three groups: control (CON), ethinylestradiol/drospirenone COC (EE/DRSP)-treated, and ethinylestradiol/levonorgestrel COC (EE/LN)-treated rats. The treatment lasted for 8 weeks. Results Results showed that with the exception of lipid profiles, EE/LN but not EE/DRSP COC treatment affected body weight, glucose tolerance, plasma insulin, corticosterone, (IR), and pancreatic β-cell dysfunction. Conclusion Taken together, the findings showed that the beneficial effect of EE/DRSP could possibly be through the DRSP component. The result also implies that COCs containing DRSP may be a better and safer means of contraception than those with LN with less cardiovascular risks.

Background With its low side effects profile and availability as an over-the-counter drug, paracetamol has been utilized extensively worldwide as an antipyretic and analgesic agent for decades. This is associated with the increasing concern over its ease of access and/or unawareness of the consumers to this issue of paracetamol-induced hepatotoxicity. Paracetamol-induced liver injury today is a big problem where most of the researchers are interested in the possible role of the naturally available antioxidants to ameliorate hepatotoxicity through kinetic interference. So the present study was designed to evaluate the effect of vitamin C and omega-3 on the pharmacokinetic property of paracetamol. Methods Six young (average age 29) healthy volunteers participated in the study. The study included three consecutive periods, each of which preceded by overnight fasting and separated by 6 day washout periods. The first period involved the ingestion of a single paracetamol dose. The second one included the ingestion of paracetamol and vitamin C concomitantly, and the final period included paracetamol plus omega-3. Saliva samples were collected and prepared for High-performance liquid chromatography analysis. Results There was a significant increase in saliva paracetamol level after 30 min of administration when given concomitantly with vitamin C compared with the remaining groups. No significant differences in the paracetamol concentration profile between the subjects for each group were observed at 60, 90, 120 and 150 min in all treated groups. Conclusion Concurrent administration of vitamin C with paracetamol increases significantly the C max level (maximum measured concentration) in saliva and increases the extent of absorption and the possibility of drug-drug interaction and risk of side effects.

Background Subtenon anticancer drugs are given as an adjunct to systemic chemotherapy for conditions like retinoblatoma. This study evaluated the ocular kinetics of nano-emulsion formulation of etoposide (NanoEt) and compared it with an equal dose of commercially available alcohol-based etoposide formulation in healthy rabbits. Methods A nanoemulsion formulation of NanoEt was developed and then evaluated for its ocular kinetics by subtenon administration in healthy rabbits. After the sterile subtenon administration of the drug, the eyes were enucleated after CO 2 euthanasia at time intervals of 2 h, 6 h, 12 h, and 24 h, and ocular tissues, blood, and plasma were separated. The concentration of etoposide in the ocular tissues and blood was quantified using liquid chromatography tandem mass spectrometry (LC MS/MS). Results This study found that subtenon injection of NanoEt showed 24 times higher concentration in rabbit retina compared to an equal dose of conventional marketed formulation. Based on the ocular tissue bioavailability calculations (AUC 0-24 ), the present study revealed that the formulation enhanced 90% ocular bioavailability of etoposide, when it was injected in the form of nano-emulsion in most of the tissues. Conclusions NanoEt has better bioavailability compared to the commercial alcohol-based formulation for subtenon injection. Low systemic exposure showed further advantage for its projected use in retinoblastoma (Rb) as an adjunct therapy. Further studies in Rb animal models are required to evaluate its safety and efficacy, for its clinical utility.

Background Ulcerative colitis is a chronic mucosal inflammation of the large intestine mainly affecting the colon and rectum. The lack of effective and safe therapeutic agents led to the identification of new therapeutic agents to effectively manage the symptoms and complications of ulcerative colitis. The present study aimed to evaluate the protective effect of sodium benzoate in acetic acid-induced ulcerative colitis in rats. Methods Infusion of 3% acetic acid in the colon through the rectum was done to construct a rat model of ulcerative colitis. After 5 days of infusion, macroscopic, biochemical, and histopathological examinations and disease activity scoring of the colon were done to assess colonic damage. Results Acetic acid infusion resulted in severe inflammation in the colon assessed macroscopically and histopathologically. Moreover, it also led to increase in myeloperoxidase (MPO) and reduction in glutathione (GSH) levels. In the present study, repeated administration of sodium benzoate (400 and 800 mg/kg i.p.) and sulfasalazine (500 mg/kg orally ) for 7 days, i.e. 2 days before and continued for 5 days after acetic acid infusion, significantly attenuated macroscopic damage and disease activity score as compared to disease control. Further, it also significantly reduced the levels of MPO and enhanced colonic levels of reduced GSH. However, the lower dose of sodium benzoate (200 mg/kg) did not show sufficient protective effect in acetic acid-induced ulcerative colitis. Further, sodium benzoate per se did not show any effect in normal rats. Conclusions The observed protective effect of sodium benzoate may be due to its antioxidant and anti-inflammatory activities in an ulcerative colitis model.

Background In Nigerian traditional medicine, Rauwolfia vomitoria has been reported to be useful in the management of various human diseases, but there is no relevant information to substantiate its involvement in managing diseases arising from vascular dysfunction and oxidative stress. However, this study sought to investigate the antioxidant property of R. vomitoria and its effect on phophodiesterase-5 activity in vitro . Methods The antioxidant property was assessed through ferric-reducing antioxidant power (FRAP), copper chelation, and ABTS radical-scavenging activity. In addition, the effect of R. vomitoria on phosphodiesterase-5 (PDE-5) activity was assessed in vitro . Furthermore, analysis of phenolic compounds present in R. vomitoria was carried out using high-performance liquid chromatography (HPLC). Results The findings in this study revealed that R. vomitoria inhibited PDE-5 in a dose-dependent manner (IC 50 = 252.42 μg/mL). Furthermore, the antioxidant activity of R. vomitoria was established through FRAP (19.68 mg AAE/g), ABTS radical-scavenging ability (74.25 mmol TEAC/g), and Cu 2+ -chelating ability (IC 50 = 0.13 mg/mL). Conclusions The antioxidant property of R. vomitoria and its inhibitory effect on PDE-5 could be useful in the management of diseases arising from vascular dysfunction and oxidative stress.

Background Clopidogrel is an adenosine diphosphate receptor antagonist used in patients with atherosclerotic vascular disease to reduce the incidence of ischemic events. Case Presentation A 62-year-old woman developed a spontaneous hemarthrosis of her left knee following clopidogrel treatment. To date, no case of spontaneous hemarthrosis following clopidogrel monotherapy was reported. Prompt aspiration after discontinuing clopidogrel by conservative management can assist early diagnosis and prevent further damage to the joint. The assessment of the causality of the event was carried out via Naranjo Causality Assessment Scale. A score of 5 was reported for this patient, indicating clopidogrel as a probable cause of this reaction. Conclusion We conclude that spontaneous hemarthrosis is a possible complication following clopidogrel therapy and it needs assessment when appropriate clinical symptoms (e.g. intra-articular effusion, pain) are present.