{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:20:43Z","timestamp":1788254443949,"version":"build-2803163510"},"reference-count":30,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordination for the Improvement of Higher Education Personnel","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"https:\/\/ror.org\/03swz6y49","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background\/Objectives: The increasing therapeutic use of cannabinoid-based formulations highlights the need to better characterize their safety profile, particularly in organs involved in xenobiotic elimination, such as the kidneys. This study evaluated the renal effects of cannabidiol (CBD) and \u03949-tetrahydrocannabinol (\u03949-THC) nanoemulsions following subchronic oral administration in male Wistar rats. Methods: Forty animals (n = 8\/group) were randomly allocated into five groups: vehicle control (Licuri oil + Pluronic\u00ae F127), CBD 2.5 mg\/kg, CBD 5 mg\/kg, CBD+THC 2.5 mg\/kg, and CBD+THC 5 mg\/kg. Treatments were administered daily by oral gavage for 21 consecutive days. Kidney samples were analyzed by histopathology and immunohistochemistry (Ki-67, GST-P, and cleaved caspase-3). Results: High-dose groups (5 mg\/kg) exhibited marked histopathological alterations, including tubular and glomerular damage, hemorrhagic areas, inflammatory infiltration, and necrosis. These groups also showed increased Ki-67 and cleaved caspase-3 immunoexpression compared to controls. GST-P expression was significantly increased only in the CBD 5 mg\/kg group. No significant changes were observed in the low-dose groups. Conclusions: These findings suggest dose-dependent morphological and molecular alterations in renal tissue associated with cannabinoid nanoemulsion exposure under experimental conditions.<\/jats:p>","DOI":"10.3390\/pathophysiology33030065","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:31:13Z","timestamp":1788251473000},"page":"65","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subchronic Exposure to Low-Dose Cannabidiol (CBD) and \u03949-Tetrahydrocannabinol (\u03949-THC) Nanoemulsions Suggests Low Renal Toxicity: A Preliminary Study"],"prefix":"10.3390","volume":"33","author":[{"given":"Thiago","family":"Guedes Pinto","sequence":"first","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society, Federal University of S\u00e3o Paulo, UNIFESP, Santos 11015-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara dos Anjos","family":"Rosario","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society, Federal University of S\u00e3o Paulo, UNIFESP, Santos 11015-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Everson Alexandre","family":"de Aquino","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Ceara, UFC, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauce Socorro de Barros","family":"Viana","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Ceara, UFC, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-5403","authenticated-orcid":false,"given":"N\u00e1gila Maria Pontes Silva","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilberto Rocha","family":"Silveira","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e9bora Hellen Almeida de","family":"Brito","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vila","family":"Zampieri","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry, Federal University of Ceara, Fortaleza 60020-181, CE, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-3183","authenticated-orcid":false,"given":"Milena de Barros","family":"Viana","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society, Federal University of S\u00e3o Paulo, UNIFESP, Santos 11015-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5057-4983","authenticated-orcid":false,"given":"Daniel Araki","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society, Federal University of S\u00e3o Paulo, UNIFESP, Santos 11015-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1663\/0013-0001(2003)057[0295:AEFTTO]2.0.CO;2","article-title":"Archaeological evidence for the tradition of psychoactive plant use in the Old World","volume":"57","author":"Merlin","year":"2003","journal-title":"Econ. Bot."},{"key":"ref_2","unstructured":"Garwood, P. (1991). Sacred and profane substances: The ritual use of narcotics in later Neolithic Europe. Sacred and Profane, Oxford Committee for Archaeology."},{"key":"ref_3","first-page":"1","article-title":"Cannabis sativa L., una planta singular","volume":"45","author":"Brindis","year":"2014","journal-title":"Rev. Mex. Cienc. Farm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/cbdv.200790144","article-title":"History of cannabis and its preparations in saga, science, and sobriquet","volume":"4","author":"Russo","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R8","DOI":"10.1016\/j.cub.2019.10.039","article-title":"Cannabis sativa.","volume":"30","author":"Schilling","year":"2020","journal-title":"Curr. Biol."},{"key":"ref_6","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2023). European Drug Report 2023, Publications Office of the European Union."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4112","DOI":"10.2174\/13816128113199990620","article-title":"Acute and long-term effects of cannabis use: A review","volume":"20","author":"Karila","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_8","unstructured":"Laranjeira, R. (2014). II Levantamento Nacional de \u00c1lcool e Drogas (LENAD), INPAD\/UNIFESP."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Andre, C.M., Hausman, J.F., and Guerriero, G. (2016). Cannabis sativa: The Plant of the Thousand and One Molecules. Front. Plant Sci., 7.","DOI":"10.3389\/fpls.2016.00019"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Shiponi, S., and Bernstein, N. (2021). The Highs and Lows of P Supply in Medical Cannabis: Effects on Cannabinoids, the Ionome, and Morpho-Physiology. Front. Plant Sci., 12.","DOI":"10.3389\/fpls.2021.657323"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"116969","DOI":"10.1016\/j.indcrop.2023.116969","article-title":"Nitrogen deficiency stimulates cannabinoid biosynthesis in medical cannabis plants by inducing a metabolic shift towards production of low-N metabolites","volume":"202","author":"Song","year":"2023","journal-title":"Ind. Crop Prod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.indcrop.2018.11.039","article-title":"Interplay between chemistry and morphology in medical cannabis (Cannabis sativa L.)","volume":"129","author":"Bernstein","year":"2019","journal-title":"Ind. Crop Prod."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Christensen, C., Rose, M., Cornett, C., and Aleeso, M. (2023). Decoding the Postulated Entourage Effect of Medicinal Cannabis: What It Is and What It Isn\u2019t. Biomedicines, 11.","DOI":"10.3390\/biomedicines11082323"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1590\/S1516-44462010000500001","article-title":"Cannabis sativa: A planta que pode produzir efeitos indesej\u00e1veis e tamb\u00e9m trat\u00e1-los","volume":"32","author":"Zuardi","year":"2010","journal-title":"Rev. Bras. Psiquiatr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1266","DOI":"10.1016\/j.amjmed.2019.05.017","article-title":"Cannabis and cannabinoids: Kinetics and interactions","volume":"132","author":"Foster","year":"2019","journal-title":"Am. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1089\/can.2018.0009","article-title":"Cannabis for the management of cancer symptoms: THC version 2.0?","volume":"3","year":"2018","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_17","unstructured":"Andrade Filho, A., Campolina, D., and Dias, M.B. (2013). Toxicologia na Pr\u00e1tica Cl\u00ednica, Folium. [2nd ed.]."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3138\/canlivj.2018-0023","article-title":"Cannabis and the liver: Things you wanted to know but were afraid to ask","volume":"2","author":"Zhu","year":"2019","journal-title":"Can. Liver J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000497361","article-title":"Development of a novel nanoemulsion formulation to improve intestinal absorption of cannabidiol","volume":"2","author":"Nakano","year":"2019","journal-title":"Med. Cannabis Cannabinoids"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000534473","article-title":"Absorption and bioavailability of novel UltraShearnanoemulsion of cannabidiol in rats","volume":"6","author":"ElSohly","year":"2023","journal-title":"Med. Cannabis Cannabinoids"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1089\/can.2019.0098","article-title":"Nonlinear Disposition and Metabolic Interactions of Cannabidiol Through CYP3A Inhibition In Vivo in Rats","volume":"5","author":"Nagao","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1007\/s00204-024-03712-7","article-title":"Cytogenotoxicity and inflammatory response in liver of rats exposed to different doses of cannabis nanoemulsions","volume":"98","author":"Rosario","year":"2024","journal-title":"Arch. Toxicol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1007\/s11356-016-6141-3","article-title":"Acute crack cocaine exposure induces genetic damage in multiple organs of rats","volume":"23","author":"Moretti","year":"2016","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.pathophys.2019.07.001","article-title":"The protective effect of grape skin or purple carrot extracts against cadmium intoxication in kidney of rats","volume":"26","author":"Claudio","year":"2019","journal-title":"Pathophysiology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1177\/0960327109354312","article-title":"Subchronic toxicity of cannabis leaves on male albino rats","volume":"29","author":"Yassa","year":"2010","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1016\/j.celrep.2018.06.110","article-title":"Ki67 is a graded rather than a binary marker of proliferation versus quiescence","volume":"24","author":"Miller","year":"2018","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1590\/S0004-28032001000200011","article-title":"Apoptose como mecanismo de les\u00e3o nas doen\u00e7as hepatobiliares","volume":"38","author":"Parolin","year":"2001","journal-title":"Arq. Gastroenterol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Mohammadpour-Asl, S., Roshan-Milani, S., Abdollahzade Fard, A., and Golchin, A. (2023). In vitro evaluation of cell viability and expression profile of growth factors in mouse Sertoli cells exposed to delta-9-tetrahydrocannabinol. BMC Pharmacol. Toxicol., 24.","DOI":"10.1186\/s40360-023-00704-8"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kolbe, M.R., Hohmann, T., Hohmann, U., Ghadban, C., Mackie, K., Z\u00f6ller, C., Prell, J., Illert, J., Strauss, C., and Dehghani, F. (2021). THC reduces Ki-67-immunoreactive cells derived from human primary glioblastoma in a GPR55-dependent manner. Cancers, 13.","DOI":"10.3390\/cancers13051064"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kumar, V., Khaitan, A., Maceyka, M., Singh, N.P., Panigrahi, S., Venkataraman, A., Vinu, S., Delgado-Vega, A.M., Doyle, T., and Jain, P. (2019). Cannabinoid attenuation of intestinal inflammation in chronic SIV-infected rhesus macaques involves T cell modulation and differential expression of micro-RNAs and pro-inflammatory genes. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00914"}],"container-title":["Pathophysiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/65\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:07:53Z","timestamp":1788253673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1873-149X\/33\/3\/65"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,1]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathophysiology33030065"],"URL":"https:\/\/doi.org\/10.3390\/pathophysiology33030065","relation":{},"ISSN":["1873-149X"],"issn-type":[{"value":"1873-149X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,1]]}}}