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Therefore, our study aimed to explore the possible cardioameliorative effects of two different dosages of LIR on MTX\u2010induced cardiotoxicity in rats. Four groups of rats were divided into a control group, a group that received a single dose of 20\u2009mg\/kg of MTX by intraperitoneal injection (ip) (MTX\u2010alone group), a group that received a subcutaneous (sc) dosage of 0.2\u2009mg\/kg\/day of LIR for 2 weeks (low\u2010dose LIR group), and a group that received a sc dosage of 0.4\u2009mg\/kg\/day of LIR for 2 weeks (high\u2010dose LIR group). The latter two groups were given MTX on day 10. After 2 weeks, each group was assessed by an electrocardiography (ECG) and by measuring serum levels of cardiac enzymes and histopathological and caspase\u20103 immunohistochemical levels in heart tissues. In addition, cardiac tissue was evaluated for oxidative stress and inflammatory and apoptotic markers. When compared with the MTX\u2010alone group, the LIR\u2010treated groups had improved ECG results and significantly decreased levels of the cardiac enzyme malondialdehyde (creatine kinase (CK) and troponin), autophagy markers (including the microtubule\u2010associated proteins 1\u2009A\/1B light chain 3B [MAP1LC3B] and Beclin\u20101), tumor necrosis factor alpha (TNF\u2010\u03b1), and interleukin\u20101 beta (IL\u20101\u03b2). The LIR\u2010treated groups also had significantly increased superoxide dismutase activity compared with the MTX\u2010alone group. In addition, the LIR\u2010treated groups had much less cardiac tissue destruction and had mitigated the increased caspase\u20103 immunoexpression that had been produced by MTX. These improvements were greater in the group that received the higher dosage of LIR than in the group that received the lower dosage of LIR. In conclusion, LIR improved MTX\u2010induced cardiotoxicity more significantly at a dosage of 0.4\u2009mg\/kg\/day, probably through the interruption of oxidative stress and autophagy pathways and the activation alleviation of inflammatory cytokines.<\/jats:p>","DOI":"10.1002\/jbt.70606","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T11:08:09Z","timestamp":1763723289000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Liraglutide Ameliorates Methotrexate\u2010Induced Cardiotoxicity in Rats: Modulation of Oxidative Stress, Autophagy, and the TNF\u2010\u03b1\/NF\u2010\u03baB Signaling Inflammatory Pathway"],"prefix":"10.1002","volume":"39","author":[{"given":"Dina A.","family":"Ali","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Department, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6251-8516","authenticated-orcid":false,"given":"Eman","family":"Kolieb","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Islam O.","family":"Abdel Fattah","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Embryology, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shymaa A.","family":"Maher","sequence":"additional","affiliation":[{"name":"Medical Biochemistry and Molecular Biology Department, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1683-8436","authenticated-orcid":false,"given":"Amr","family":"Elkelish","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-8807","authenticated-orcid":false,"given":"Nasir A.","family":"Abdalneim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU) Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Abozied","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department, Faculty of Medicine Suez Canal University Ismailia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327112468178"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S178767"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15060674"},{"key":"e_1_2_9_5_1","first-page":"3978","article-title":"Liraglutide Alleviates Vascular Injury in Diabetic Rabbits With Lower Limb Vascular Stenosis Through Regulation of RCAN1","volume":"26","author":"Ding H. 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