{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:43Z","timestamp":1787029063696,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T00:00:00Z","timestamp":1635811200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chemicals can induce nephrotoxicity, with damage to different segments of the nephron and deterioration of renal function. Nephrotoxicity due to exposure to a toxin such as carbon tetrachloride, sodium oxalate, or heavy metals is the most common cause of kidney injury. The current study aimed to evaluate the protective effects of Celastrus paniculatus seed extract against lead-acetate-induced nephrotoxicity by evaluating the histopathology, immunohistochemistry, ultrastructure, and phosphoinositide 3-kinase (PI3K)\/protein kinase B (AKT) signaling pathway. Twenty-four rats were divided into four groups (n = 6 per group): group 1 contained normal animals and served as the control; group 2 received lead acetate (30 mg\/kg body weight (b.w.)\/day, oral); group 3 received lead acetate and the standard drug N-acetylcysteine (NAC, 200 mg\/kg b.w.\/day, oral); and group 4 received lead acetate and the ethanolic extract of C. paniculatus seed (EECP; 800 mg\/kg b.w.\/day, oral). Treatment was given for 28 consecutive days. The data were analyzed using one-way analysis of variance with SIGMA PLOT 13 using SYSTAT software followed by Newman\u2013Keul\u2019s test for comparison between the groups. EECP ameliorated the adverse changes caused by lead acetate. PI3K and AKT messenger RNA (mRNA) levels were diminished in lead-acetate-treated rats. Treatment with EECP inhibited the occurrence of shrunken cells, the atrophy of glomeruli, and degenerative changes in renal tubules caused by lead acetate. Interestingly, the PI3K and AKT mRNA levels were significantly increased in EECP-treated animals. Our results clearly evidence for the first time that C. paniculatus seed extract inhibits lead-acetate-induced detrimental changes in kidneys by regulating PI3K\/AKT signaling pathways.<\/jats:p>","DOI":"10.3390\/molecules26216647","type":"journal-article","created":{"date-parts":[[2021,11,2]],"date-time":"2021-11-02T22:17:23Z","timestamp":1635891443000},"page":"6647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular Studies on the Nephroprotective Potential of Celastrus paniculatus against Lead-Acetate-Induced Nephrotoxicity in Experimental Rats: Role of the PI3K\/AKT Signaling Pathway"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4361-1293","authenticated-orcid":false,"given":"Karunakaran","family":"Balaji","sequence":"first","affiliation":[{"name":"Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, Chennai 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagadish","family":"Vijayakumar","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, Chennai 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ponnusamy Kasirajan","family":"Sankaran","sequence":"additional","affiliation":[{"name":"Department of Anatomy, All India Institute of Medical Sciences, Mangalagiri 522503, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivanesan","family":"Senthilkumar","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Saveetha Institute of Medical & Technical Sciences, Chennai 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-5404","authenticated-orcid":false,"given":"Rajagopalan","family":"Vijayaraghavan","sequence":"additional","affiliation":[{"name":"Department of Research and Development, Saveetha Institute of Medical & Technical Sciences, Chennai 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayaraman","family":"Selvaraj","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Saveetha Institute of Medical & Technical Sciences, Saveetha Dental College & Hospital, Chennai 600077, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Francis","family":"Yuvaraj","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Saveetha Institute of Medical & Technical Sciences, Chennai 602105, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.envint.2016.09.014","article-title":"Diclofenac and its transformation products: Environmental occurrence and toxicity\u2014A review","volume":"96","author":"Lonappan","year":"2016","journal-title":"Environ. 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