Tramadol is an opioid extensively used to treat moderate to severe pain; however, prolonged therapy is associated with several tissues damage. Chronic use of tramadol was linked to increased hospitalizations due to cardiovascular complications. Limited literature has described the effects of tramadol on the cardiovascular system, so we sought to investigate these actions and elucidate the underlying mechanisms. Mice received tramadol hydrochloride (40 mg/kg body weight) orally for 4 successive weeks. Oxidative stress, inflammation, and cardiac toxicity were assessed. In addition, eNOS expression was evaluated. Our results demonstrated marked histopathological alteration in heart and aortic tissues after exposure to tramadol. Tramadol upregulated the expression of oxidative stress and inflammatory markers in mice heart and aorta, whereas downregulated eNOS expression. Tramadol caused cardiac damage shown by the increase in LDH, Troponin I, and CK-MB activities in serum samples. Overall, these results highlight the risks of tramadol on the cardiovascular system.

Background: Synthetic cannabinoids are one of the largest groups of new psychoactive substances that invaded Egypt’s drug abuse market over the past few years. Aim: Randomized controlled trial study to demonstrate the effects of acute and chronic toxicity by synthetic cannabinoid (Strox) on the brain, liver, heart, and testes in adult male albino rats through histopathological examination by light microscope and immunohistochemistry. Methods: Total number of fifty male albino rats were divided into five different groups, two control and three treated groups. Negative and positive control groups received distilled water and dimethyl sulfoxide, respectively, acute group received LD₅₀ (lethal dose 50) once and observed for 14 days, chronic group received 1/10 LD₅₀ for 3 months, and finally chronic withdrawal groups received 1/10 LD₅₀ for 3 months and then left 2 weeks without the substance to observe the withdrawal manifestations. Results: The current study revealed various histopathological changes in all organs with increased expression of cannabinoid receptor 1. The most important findings observed by light microscope examination were shrinkage and degenerative changes in Purkinje cells in brain sections, abnormalities in blood sinusoids and architecture in liver section, disruption in cardiac muscle fiber in heart sections, and finally testes showed irregularities in seminiferous tubules and germinal cells. Immunohistochemical staining for caspase-3 in the brain, liver, and heart showed weak-positive reaction in acute group and a strong reaction with chronic groups. Additionally, increase in collagen fiber was observed in sections of the liver and heart of chronic group. Conclusions: Synthetic cannabinoid sample (Strox) toxicity caused adverse effects on the brain, liver, heart, and testes as shown by increasing cannabinoid receptor 1 and caspase-3 expression.

Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress in DR. Methods: A total of 18 male Wistar rats were divided into a control group (n = 6) and a streptozotocin-induced diabetic group (n = 12), which were further divided into diabetic control and FSK-treated groups (n = 6 each). Total antioxidant capacity (TAC), total peroxide (TP), triglycerides (TGs), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured. qRT-PCR analysis for miRNA-200b and immunohistochemistry were performed. Results: Diabetic rats showed oxidative stress and hyperlipidemia associated with increased circulating miR-200b levels. The retina showed reduced neuron numbers (Caspase-3), altered glial and astrocyte staining (IBA1, GFAP), and changes in microglia/macrophage morphology and distribution. Intravitreal FSK improved retinal ganglion cell survival and reduced glial activation, while systemic lipid profile and oxidative stress markers remained largely unchanged. Circulating miR-200b levels showed a positive correlation with oxidative stress markers across groups. Conclusions: Intravitreal FSK was able to limit the disease exacerbation via improved neuronal survival through inhibition of apoptosis. FSK did not produce observable qualitative changes in GFAP expression or IBA1+ cell morphology under the conditions tested.