ArticleBritish journal of pharmacology2015
Endothelin ETA receptor/lipid peroxides/COX-2/TGF-β1 signalling underlies aggravated nephrotoxicity caused by cyclosporine plus indomethacin in rats.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 37 citations in OpenAlex.
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- Sulfasalazine mitigates cisplatin-induced nephrotoxicity via NF-κB downregulation and upstream modulation of p-AMPK, SIRT1, miRNA-132-3p, and miRNA-375.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Gestationally administered RAS modulators reprogram endotoxic cardiovascular and inflammatory profiles in adult male offspring of preeclamptic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Suppression by central adenosine A3 receptors of the cholinergic defense against cardiovascular aberrations of sepsis: role of PI3K/MAPKs/NFκB signaling.Frontiers in pharmacology · 2024Article
- Adenosine A1 receptors of the medullary solitary tract arbitrate the nicotine counteraction of neuroinflammation and cardiovascular dysfunction in septic rats.Scientific reports · 2023Article
- Montelukast potentiates the antiinflammatory effect of NSAIDs in the rat paw formalin model and simultaneously minimizes the risk of gastric damage.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- The α7-nAChR/heme oxygenase-1/carbon monoxide pathway mediates the nicotine counteraction of renal inflammation and vasoconstrictor hyporeactivity in endotoxic male rats.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Time and sex dependency of hemodynamic, renal, and survivability effects of endotoxemia in rats.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2020Article
- Possible protective effect of the algae spirulina against nephrotoxicity induced by cyclosporine A and/or gamma radiation in rats.Environmental science and pollution research international · 2018Article
- The inflammatory state provokes sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats.Scientific reports · 2017Article
- Article
- Renal Oxidative Stress and Inflammatory Response in Perinatal Cyclosporine-A Exposed Rat Progeny and its Relation to Gender.Journal of microscopy and ultrastructureArticle
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeCyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling. EXPERIMENTAL APPROACH: The effects of a 10 day treatment with CSA (20 mg · kg(-1) · day(-1)), indomethacin (5 mg · kg(-1) · day(-1)) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ETA receptor and COX-2 pathways in the interaction were evaluated. KEY
resultsOral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ETA receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ETA receptor and COX-2 expressions. Blockade of ETA receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ETA receptor and COX-2 protein. CONCLUSIONS AND IMPLICATIONS: The exaggerated oxidative insult and associated dysregulation of the ETA receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ETA receptor antagonism might be exploited therapeutically.
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