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It has a significant negative impact on patients\u2019 quality of life; as it starts with loss of limbs\u2019 sensation and may lead to lower limb amputation. This study aimed at investigating the effect of liraglutide on peripheral neuropathy in diabetic rats. Experimental diabetes was induced by single intraperitoneal injections of nicotinamide (50\u00a0mg\/kg) and streptozotocin (52.5\u00a0mg\/kg). Rats were allocated into five groups. Two groups were given saline or liraglutide (0.8\u00a0mg\/kg, s.c.). Three diabetic groups were either untreated or treated with liraglutide (0.8\u00a0mg\/kg, s.c.) or pregabalin (10\u00a0mg\/kg, i.p.). After 2\u00a0weeks of treatment, behavioral, biochemical, histopathological, and immunohistochemical investigations were performed. Treatment with liraglutide\u2010restored animals\u2019 body weight, normalized blood glucose, decreased glycated hemoglobin, and increased insulin levels. In parallel, it normalized motor coordination and the latency withdrawal time of both tail flick and hind paw cold allodynia tests and reversed histopathological alterations. Treatment with liraglutide also normalized malondialdehyde, matrix metalloproteinase\u20102 and \u20109 contents in sciatic nerve. Likewise, it decreased sciatic nerve nitric oxide and interleukin\u20106 contents,<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>fragmentation and expression of cyclooxygenase\u20102. Meanwhile, it increased superoxide dismutase and interleukin\u201010 contents in sciatic nerve. These findings indicate the neuroprotective effect of liraglutide against diabetic peripheral neuropathy probably via modulating oxidative stress, inflammation, and extracellular matrix remodeling.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14336-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14336","type":"journal-article","created":{"date-parts":[[2018,3,24]],"date-time":"2018-03-24T05:16:36Z","timestamp":1521868596000},"page":"173-185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Liraglutide ameliorated peripheral neuropathy in diabetic rats: Involvement of oxidative stress, inflammation and extracellular matrix remodeling"],"prefix":"10.1111","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2690-5997","authenticated-orcid":false,"given":"Passant E.","family":"Moustafa","sequence":"first","affiliation":[{"name":"Department of Pharmacology National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7026-283X","authenticated-orcid":false,"given":"Noha F.","family":"Abdelkader","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2840-1776","authenticated-orcid":false,"given":"Sally A.","family":"El Awdan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama A.","family":"El\u2010Shabrawy","sequence":"additional","affiliation":[{"name":"Department of Pharmacology National Research Centre Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9026-4015","authenticated-orcid":false,"given":"Hala F.","family":"Zaki","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Cairo University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,27]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13087"},{"key":"e_1_2_8_3_1","first-page":"169","article-title":"Antidiabetic, hypolipidemic and hepatoprotective effects of Arctium lappa root's hydro\u2010alcoholic extract on nicotinamide\u2010streptozotocin induced type 2 model of diabetes in male mice","volume":"7","author":"Ahangarpour A.","year":"2017","journal-title":"Avicenna J. 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