{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T07:25:29Z","timestamp":1774941929620,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T00:00:00Z","timestamp":1752710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Autonomic imbalance is one of the major pathological disturbances in chronic heart failure (CHF). Additionally, enhanced oxidative stress and inflammation are considered to be the main contributors to the disease progression. A growing body of evidence suggests cholinergic stimulation as a potential therapeutic approach in CHF, since it corrects the autonomic imbalance and alters the inflammatory response via the cholinergic anti-inflammatory pathway. Although previous research has provided some insights into the potential mechanisms behind these effects, there is a gap in knowledge regarding different cholinergic stimulation methods and their specific mechanisms of action. In the present study, an isoprenaline model (5 mg\/kg\/day s.c. for 7 days, followed by 4 weeks of CHF development) was used. Afterwards, rats received pyridostigmine (22 mg\/kg\/day in tap water for 14 days) or no treatment. Pyridostigmine treatment prevented the progression of CHF, decreasing chamber wall thinning (\u2191 PWDd, \u2191 PWDs) and left ventricle dilatation (\u2193 LVIDd, \u2193 LVIDs), thus improving cardiac contractile function (\u2191 EF). Additionally, pyridostigmine improved antioxidative status (\u2193 TBARS, \u2193 NO2\u2212; \u2191 CAT, \u2191 GSH) and significantly reduced cardiac fibrosis development, confirmed by pathohistological findings and biochemical marker reduction (\u2193 MMP2, \u2193 MMP9). However, further investigations are needed to fully understand the exact cellular mechanisms involved in the CHF attenuation via pyridostigmine.<\/jats:p>","DOI":"10.3390\/ijms26146892","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T11:12:34Z","timestamp":1752837154000},"page":"6892","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pyridostigmine Treatment Significantly Alleviates Isoprenaline-Induced Chronic Heart Failure in Rats"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-9428","authenticated-orcid":false,"given":"Sonja T.","family":"Marinkovi\u0107","sequence":"first","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"},{"name":"Pediatric Clinic, University Clinical Centre of the Republic of Srpska, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6141-1338","authenticated-orcid":false,"given":"Tanja","family":"Sobot","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1190-6636","authenticated-orcid":false,"given":"\u017dana M.","family":"Maksimovi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"},{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"\u00d0or\u0111e","family":"\u00d0ukanovi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"},{"name":"Department of Pharmaceutical Chemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4219-5806","authenticated-orcid":false,"given":"Sne\u017eana","family":"Uletilovi\u0107","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of Srpska, Bosnia and Herzegovina"},{"name":"Department of Medical Biochemistry and Chemistry, Faculty of Medicine, University of Banja Luka, 78000 Banja Luka, The Republic of 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