Browsing by Subject "Inducible nitric oxide synthase"

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    Current review on inducible nitric oxide synthase and Src tyrosine kinase inhibitors as disease-modifiers in preclinical models of epilepsy
    (2026) Thimmasettappa Thippeswamy; Suraj Sundara Vasanthi; Biología Celular e Histología; Universidad de Murcia, Departamento de Biologia Celular e Histiologia
    Acute exposure to seizurogenic chemicals, such as organophosphates (OPs) or domoic acid (kainate analogue), can trigger status epilepticus (SE), marked by central (seizures) and, with OPs, peripheral effects due to irreversible inhibition of acetylcholinesterase (AChE). The initial seizurogenic activity in the brain initiates a cascade of molecular and cellular changes, known as epileptogenesis, the process by which epilepsy develops. Among the several signaling pathways involved in epileptogenesis, this review discusses the roles of the Src family of tyrosine kinases (SFK), especially Fyn kinase, and inducible nitric oxide synthase (iNOS) mediated mechanisms. Both signaling molecules are upregulated following initial seizures and persist for a long time, contributing to neuroinflammation, elevated levels of reactive oxygen and nitrogen species (ROS/RNS), and proinflammatory cytokines, as well as neuro degeneration and spontaneously recurring seizures. Epilepsy is a progressive disease associated with unprovoked seizures and cognitive decline. While the current standard of care can alleviate symptoms and reduce mortality, they do not address long-term neurological consequences. In this review, we discuss preclinical testing of two CNS-targeted drugs, iNOS and SFK inhibitors 1400W and Saracatinib (SAR; AZD0530), respectively, as potential disease-modifiers.
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    Evaluation of HIF-1α and iNOS in ischemia/reperfusion gastric model: bioimpedance, histological and immunohistochemical analyses
    (Universidad de Murcia. Departamento de Biología Celular e Histología, 2018) Peña Mercado, Eduardo; Garcia Lorenzana, Mario; Arechaga Ocampo, Elena; González De la Rosa, Claudia H.; Beltran, Nohra E.
    Gastrointestinal ischemia/reperfusion (I/R) generates pathological alterations that could lead to death. Early ischemic damage markers could be used to guide therapy and improve outcomes. Aim. To relate hypoxia-inducible factor 1α (HIF-1α) activation and inducible nitric oxide synthase (iNOS) expression to gastric impedance changes due to I/R damage. Methods. Experimental animals were randomly distributed into 3 groups: control, ischemia (30 min) and I/R (60 min). Gastric ischemia was generated by celiac artery clamping for 30 min, and then blood flow was restored for 60 min. Impedance spectra and biopsies of the glandular portion were obtained for histological and immunohistochemical analyses. Immunodetection of both HIF-1α and iNOS was performed. Results. Under ischemia and I/R conditions, there was an increase (p<0.05) in the impedance parameters. Histologically, under ischemic conditions, edema and necrosis were observed in epithelium and significant vascular congestion. In I/R condition, alterations of the glandular and luminal integrity were found, which generated areas of epithelial erosion. Immunohistochemical analysis of HIF-1α revealed an increase (p<0.01) in the number of immunoreactive cells in the ischemia (35.7±13.9) and I/R (119.9±18.8) conditions compared to the control (0.8±1.2). Immunodetection of iNOS showed an increase (p<0.01) in the number of cells expressing iNOS under the ischemia (5.4±2.9) and I/R conditions (27.4±11.3) was observed compared to the control (0.4±0.8). Conclusion. Early changes in impedance in response to I/R is related to histopathological changes, the nuclear stabilization and translocation of HIF-1α as well as expression of iNOS.