AIMS: Neuroinflammatory changes in the central nervous system are widely involved in the initiation and maintenance of neuropathic pain after peripheral nerve injury. The present study investigated how losartan treatment may affect the development of neuropathic pain and neuroinflammation. MAIN METHODS: The effect of losartan treatment on the development of peripheral neuropathy was studied in L5 spinal nerve ligation (SNL) model in rats with systemic (100 mg/kg) or intrathecal (10 μl/ 20 μM solution) application of losartan. Electronic von Frey filament and plantar test were used to determine pain thresholds to mechanical and thermal stimulations. At the 7th post-operative day, CD68-positive cells in DRG and dorsal roots were quantified by immunohistochemistry and western blot analyses were used to compare the expression levels of neuroinflammatory markers in lumbar spinal cord (SC). KEY FINDINGS: Our data confirmed the presence of SNL-evoked heat hyperalgesia and mechanical allodynia. Losartan application blocked the SNL-induced hypersensitivity to thermal stimuli but failed to prevent mechanical allodynia. No significant difference between systemic and i.t. administration of losartan was observed. Immunohistochemistry confirmed the presence of infiltrated macrophages in the ipsilateral DRG that was significantly attenuated with the losartan treatment. Western blot SC tissue analysis revealed that systemic treatment with losartan prevented SNL-induced upregulation of CCR2, TNFα, TNFR1, and OX42 while its effect on CCL2 and AT1R expression was not significant. SIGNIFICANCE: Our results show that losartan treatment attenuates neuroinflammation and neuropathic pain after SNL. These effects of losartan represent an interesting direction for the development of novel treatments of peripheral neuropathy.
- MeSH
- hyperalgezie farmakoterapie prevence a kontrola MeSH
- krysa rodu rattus MeSH
- losartan metabolismus farmakologie MeSH
- měření bolesti metody MeSH
- mícha účinky léků MeSH
- míšní nervy účinky léků MeSH
- modely nemocí na zvířatech MeSH
- neuralgie metabolismus MeSH
- poranění periferního nervu farmakoterapie MeSH
- potkani Wistar MeSH
- práh bolesti účinky léků MeSH
- spinální ganglia účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- benzimidazoly agonisté metabolismus MeSH
- bifenylové sloučeniny metabolismus terapeutické užití MeSH
- blokátory receptoru 1 pro angiotenzin II farmakologie MeSH
- diabetes mellitus 2. typu metabolismus MeSH
- finanční podpora výzkumu jako téma MeSH
- hypertenze metabolismus terapie MeSH
- inzulinová rezistence MeSH
- lidé MeSH
- losartan analogy a deriváty metabolismus terapeutické užití MeSH
- metabolický syndrom metabolismus terapie MeSH
- tetrazoly metabolismus terapeutické užití MeSH
- Check Tag
- lidé MeSH
Predmetom štúdia bolo sledovať vplyv podávania antihypertenzívneho lieku losartanu na: 1) antioxidačny stav potkanov s experimentálnym inzulíndependentnym diabetes mellitus; 2) stav oxidačného poškodenia reprezentovaného tvorbou látok, ktoré reagujú s kyselinou tiobarbiturovou(TBARP) a 3) niektoré metabolické parametre. Podávanie losartanu vyznamne neovplyvnilo koncentráciu glukózy, cholesterolu, triacylglycerolov a kyseliny močovej v plazme kontrolnych a diabetickych zvierat. V pečeňovom tkanive sa po podaní losartanu znízila koncentrácia triacylglycerolov,koncentrácia cholesterolu nebola ovplyvnená. Ďalej sa zistilo, ze podávanie losartanu zvyšilohladinu antioxidantov rozpustnych v lipidoch v plazme diabetickych potkanov, čo môze byš príčinouzisteného znízenia obsahu TBARP v plazme diabetickych potkanov.
The aim of this study was to monitor the effect of the administration of antihypertensive druglosartan on: (1) the antioxidant status of rats with experimental insulin-dependent diabetesmellitus; (2) oxidative damage which is represented by the production of compounds which can reactwith thiobarbituric acid (TBARP), and (3) some metabolic parameters. Losartan administration didnot significantly influence the concentration of glucose, cholesterol, triacylglycerol, and uric acid inthe plasma of control and diabetic animals. In the liver tissue, the concentration of triacylglycerolsdecreased after losartan administration, but the concentration of cholesterol did not change. Thepresent authors have found that losartan administration increased the levels of water solubileantioxidants in the plasma of diabetic rats, which can result in a decrease of the TBARP levels inthe plasma of diabetic rats.
The presence of angiotensin II receptors was found on cells of three colorectal carcinoma cell lines. The binding assays with 125I-labelled angiotensin II and ligands specific for angiotensin AT1 or AT2 receptors showed that angiotensin receptors on colorectal cancer cells are mostly of the AT2 type. The binding capacity of tumor cells was not significantly changed by butyrate-induced differentiation.
- MeSH
- angiotensin II chemie metabolismus MeSH
- blokátory receptoru 1 pro angiotenzin II metabolismus MeSH
- buněčná membrána metabolismus MeSH
- financování organizované MeSH
- kolorektální nádory metabolismus MeSH
- lidé MeSH
- losartan metabolismus MeSH
- nádorové buněčné linie metabolismus MeSH
- oligopeptidy metabolismus MeSH
- radioizotopy jodu metabolismus MeSH
- receptor angiotensinu typ 2 genetika metabolismus MeSH
- Check Tag
- lidé MeSH
