Tramadol aggravates cardiovascular toxicity in a rat model of alcoholism: Involvement of intermediate microfilament proteins and immune-expressed osteopontin.

Tramadol and alcohol are among commonly abused drugs. Although there are potential dangers reported upon their mixing, there are no previous reports describing this mixture's effects on the cardiovascular system (CVS). The aim was to study the effects of mixed alcohol and tramadol on the CVS of adult male rats. Fifty rats were divided into four groups: control, tramadol-treated group, alcohol-treated, and coadministration groups. Tramadol caused a significant increases in creatine kinase-MB, troponin I, malondialdehyde, protein carbonyl, 8-hydroxy-2'-deoxyguanosine, and a significant decrease in total antioxidant capacity with histological alterations in sections of the heart and aorta and a significant increase in the area% of collagen fibers while there was a nonsignificant difference in body weight, heart weight, heart weight/body weight ratio, lipid profile, tissue tumor necrosis factor-α and interferon-γ, intermediate microfilament proteins (IFPs) {desmin, vimentin, connexin43} gene expression, mean area% of elastic fibers in aortic tissue and osteopontin expression in cardiac and aortic tissue. Alcohol treatment caused a significant change in all the measured parameters and more damage in histological sections. The changes were highest in the coadministration group. There was a strong positive correlation between the area% of collagen fibers and vimentin gene expression, and the area% of osteopontin expression was positively correlated to connexin43 in cardiac and vascular tissue. Tramadol causes CVS injury mainly through oxidative stresses, while the alcohol effect is multifactorial; mixing both aggravates CVS injury. The study also highlights the role of IFPs and osteopontin-expression in inducing injury.

Manganese-induced neurotoxicity and the potential protective effects of lipoic acid and Spirulina platensis.

Manganese (Mn) is essential for many physiological processes; however, its excessive accumulation in the brain causes severe dysfunctions in the nervous system. Oxidative stress is thought to be involved in Mn-induced neurotoxicity. The aim of this study was to evaluate the neurotoxic effects of Mn and the potential protective effects of alpha lipoic acid (ALA) and Spirulina platensis (SP), each alone and in combination. Sixty-four male albino rats were divided into eight equal groups: group 1 was used as control, group 2 received saline, which used as a vehicle, group 3 received ALA (50 mg/kg/day), group 4 received SP (300 mg/kg/day), group 5 received Mn (74 mg/kg, 5 days/week), group 6 received Mn + ALA, group 7 received Mn + SP, group 8 received Mn + ALA + SP. Groups 6, 7 and 8 received the same previously mentioned doses. All treatments were orally gavaged for 8 weeks. Mn administration caused neurobehavioral changes, increases of brain and serum Mn and malondialdehyde (MDA), with decreased glutathione peroxidase (GPx), dopamine and acetylcholine levels. The co-treatment with ALA and SP revealed their ability to protect against oxidative damage, neurobehavioral and biochemical changes induced by Mn.

Functional and Structural Assessment of the Effect of Human Umbilical Cord Blood Mesenchymal Stem Cells in Doxorubicin-Induced Cardiotoxicity.

Cardiomyopathy induced by doxorubicin (DOX) was recognized at an early stage and also several years after drug administration. Mesenchymal stem cells (MSCs) have many properties that make them suitable for preventive and/or regenerative therapies. In this study, we evaluated the effect of MSCs in the functional and the structural improvement of DOX-induced cardiomyopathy in rats. Ninety adult male albino rats were randomly divided into three equal groups of thirty rats each: Group I (control): rats received normal saline. Group II (DOX- group): rats received DOX. Group III (DOX-MSCs group): rats received DOX for 2 weeks then human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). Rats in all groups were evaluated for: physical condition, electrocardiography (ECG), and hemodynamic parameters. Serum cardiac troponin I (cTnI), malondialdehyde (MDA), total antioxidant capacity (TAC), and DNA fragmentation on heart tissue isolated DNA were estimated for evaluation of the mechanism and the extent of the damage. Hearts were examined histopathologically for detection of MSCs homing, structural evaluation, with counting of the collagen fibers for evaluation of fibrosis. DOX-administered rats showed significant functional and structural deterioration. DOX-MSCs treated rats (group III) showed improved functional and structural criteria with restoration of all biochemical indicators of cardiac damage and reactive oxygen species (ROS) to normal, as well. In Conclusion, hUCB-MSCs significantly ameliorated the cardiotoxic manifestations as shown by biochemical, functional, and structural cardiac improvement. J. Cell. Biochem. 118: 3119-3129, 2017. © 2017 Wiley Periodicals, Inc.

Cardiotoxicity of Freon among refrigeration services workers: comparative cross-sectional study.

BACKGROUND: Freon includes a number of gaseous, colorless chlorofluorocarbons. Although freon is generally considered to be a fluorocarbon of relatively low toxicity; significantly detrimental effects may occur upon over exposure. The purpose of the present study is to investigate whether occupational exposure to fluorocarbons can induce arterial hypertension, myocardial ischemia, cardiac arrhythmias, elevated levels of plasma lipids and renal dysfunction. METHODS: This comparative cross-sectional study was conducted at the cardiology clinic of the Suez Canal Authority Hospital (Egypt). The study included 23 apparently healthy male workers at the refrigeration services workshop who were exposed to fluorocarbons (FC 12 and FC 22) and 23 likewise apparently healthy male workers (unexposed), the control group. All the participants were interviewed using a pre-composed questionnaire and were subjected to a clinical examination and relevant laboratory investigations. RESULTS: There were no significant statistical differences between the groups studied regarding symptoms suggesting arterial hypertension and renal affection, although a significantly higher percentage of the studied refrigeration services workers had symptoms of arrhythmias. None of the workers had symptoms suggesting coronary artery disease. Clinical examination revealed that the refrigeration services workers had a significantly higher mean pulse rate compared to the controls, though no significant statistical differences were found in arterial blood pressure measurements between the two study groups. Exercise stress testing of the workers studied revealed normal heart reaction to the increased need for oxygen, while sinus tachycardia was detected in all the participants. The results of Holter monitoring revealed significant differences within subject and group regarding the number of abnormal beats detected throughout the day of monitoring (p < 0.001). There were no significant differences detected in the average heart rate during the monitoring period within subject or group. Most laboratory investigations revealed absence of significant statistical differences for lipid profile markers, serum electrolyte levels and glomerular lesion markers between the groups except for cholesterol and urinary beta2-microglobulin (tubular lesion markers) levels which were significantly elevated in freon exposed workers. CONCLUSIONS: Unprotected occupational exposure to chlorofluorocarbons can induce cardiotoxicity in the form of cardiac arrhythmias. The role of chlorofluorocarbons in inducing arterial hypertension and coronary artery diseases is unclear, although significantly elevated serum cholesterol and urinary beta2-microglobulin levels raise a concern.