Cardioprotective and renoprotective effects of venlafaxine on cisplatin-induced cardiotoxicity and nephrotoxicity in rats.

AIM: The current work aims to demonstrate the potential defensive function of venlafaxine (VLF) in cardiotoxicity and nephrotoxicity caused by cisplatin (CP), that could be by modulating extracellular signal-regulated kinase (ERK)1/2 and nicotinamide adenine dinucleotide phosphate (NAPDH) oxidase NOX4 pathways. MAIN METHODS: Five groups of rats were used, as follow: three control groups (control, carboxymethyl cellulose, and VLF), CP group got CP once (7 mg/kg, intraperitoneally, i.p.), and (CP+ VLF) group got CP once then after 1 h they got VLF {50 mg/kg daily, orally for 14 days}. At the end of the study; electrocardiogram (ECG) was recorded for anaesthized rats then blood samples and tissues were taken for biochemical and histopathological investigations. Caspase 3, a marker of cellular damage and apoptosis was detected by immunohistochemistry. KEY FINDINGS: CP treatment significantly impaired cardiac functions as evidenced by changes in rats' ECG. Cardiac enzymes, renal markers and inflammatory markers were increased with decreased activities of the total antioxidant capacity, superoxide dismutase and glutathione peroxidase. Also, ERK1/2 and NOX4 were upregulated with histopathological and immunohistochemical alterations of heart and kidney. While, VLF markedly alleviated CP-induced functional cardiac abnormalities and improved ECG pattern. It reduced both cardiac and renal biomarkers, oxidative stress, proinflammatory cytokine with ERK1/2 and NOX4 downregulation, improved the histopathological and immunohistochemical changes induced by cisplatin in heart and kidney. SIGNIFICANCE: VLF treatment impedes cardiotoxicity and nephrotoxicity caused by CP. This beneficial effect was mediated through reduction of oxidative stress, inflammation, and apoptosis by targeting the ERK1/2 and NOX4.

Acute toxic effects of new synthetic cannabinoid on brain: Neurobehavioral and Histological: Preclinical studies.

The psychoactive effects of new synthetic cannabinoids (SCs), MDMB-4en-PINACA, are being marketed as a blend of herbs and spices. This study aims to determine the behavioral, neurochemical, histopathological, and immunohistochemical alterations associated with the acute toxicity of MDMB-4en-PINACA compounds. METHODS: Adult male albino rats were administered various toxic doses of the drug (1.5, 3, and 6 mg/kg), and behavioral studies were conducted 2 and 24 h later; animals were then sacrificed. Histopathological and neurochemical examinations were performed. Two hours after intraperitoneal. RESULTS: Intraperitoneal injection of MDMB-4en-PINACA, horizontal movement, the number of stops, and mobility ratio were significantly impaired, along with coordination and balance. In addition, it led to a decline in spatial learning and memory, and neurotransmitter concentrations decreased significantly in a dose-dependent manner. Further examination of the cerebral cortex and hippocampus histopathology revealed pathological degeneration of small pyramidal cells. CONCLUSION: Thus, these findings revealed that MDMB-4en-PINACA interferes with hippocampal function and impairs cognitive performance, highlighting the cognitive risk associated with SC abuse.

Impact of tramadol abuse on clinical outcome of lumbar discectomy patients'.

BACKGROUND DATA: Little data exists regarding the effect of chronic preoperative tramadol abuse on the clinical outcomes after surgery. Lumbar discectomy is a very common procedure that has a predictably high success rate for relief of radicular pain. In addition, the patient population presenting for this procedure has a high propensity for preoperative narcotic use. PURPOSE: The study aims to identify an association between preoperative tramadol abuse and clinical outcome after lumbar discectomy. STUDY DESIGN: A descriptive controlled, non-randomized, clinical study. PATIENTS AND METHODS: Sixty patients underwent surgery for lumbar disc herniation. They were divided into two groups; control group and tramadol abuse group. Each group included 30 patients. They were operated between 2015 and 2016. Participants were evaluated pre-operatively and post-operatively every three months. Strict history taking regarding preoperative and postoperative pain medication utilization, operative time, hospital stay and complications were assessed. Pain was scored by a VAS for both lower limbs and back pain. The clinical outcomes were compared using the Prolo economic and functional rating scale. RESULTS: In Tramadol abuse group, 12 (40%) continued to use tramadol after surgery. Tramadol abuse group showed worse clinical outcome parameters including worse VAS for low back pain and lower limb pain, worse Prolo economic, functional rating scale. In addition, tramadol abuse group showed significantly higher complications rate in the early post-operative and during the follow up period. CONCLUSION: Tramadol abuse before lumbar discectomy was found to be associated with continued tramadol abuse after surgery and worse functional outcomes following surgery. Surgeons may want to counsel their patients about the potential for inferior clinical outcomes if narcotics were used before surgery.