{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:50:06Z","timestamp":1773287406536,"version":"3.50.1"},"reference-count":87,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian Ministry of Education and Science","award":["BG-RRP-2.004-0006-C02"],"award-info":[{"award-number":["BG-RRP-2.004-0006-C02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Acetaminophen (paracetamol or APAP) overdose is a major cause of acute liver injury mediated by oxidative stress, inflammation, and hepatocellular necrosis. The present study investigates the in vivo hepatoprotective potential of morin (M), lignin nanoparticles (LN), and morin-encapsulated lignin nanoparticles (LMN) against APAP-induced hepatotoxicity in mice. The specific goal was to determine whether LMN could strengthen hepatic antioxidant and anti-inflammatory defenses prior to toxic insult, which aligns with a prophylactic model rather than a post-injury clinical rescue approach. This study was guided by the primary hypothesis that LMN pretreatment would markedly reduce APAP-induced hepatic injury. Methods: Experimental groups included control, APAP, M, LN, LMN, M+APAP, LN+APAP, and LMN+APAP treatments. Serum hepatic biomarkers, oxidative stress parameters, and inflammatory cytokines were analyzed to assess protective responses. Results: APAP exposure markedly elevated aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels, indicating severe hepatic dysfunction, accompanied by increased lipid peroxidation and pro-inflammatory cytokine production. LMN+APAP treatment significantly restored hepatic enzyme levels to approximately normal values and suppressed malondialdehyde (MDA) formation, while enhancing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. LMN also downregulated interleukin 6 (IL-6), tumor necrosis factor \u03b1 (TNF-\u03b1), and interleukin 1\u03b2 (IL-1\u03b2), while upregulating interleukin 10 (IL-10), suggesting effective attenuation of inflammatory signaling. Correlation analyses demonstrated positive interactions between MDA, cytokines, and hepatic enzymes, whereas antioxidant enzyme levels were inversely correlated with liver injury markers. Histopathological analysis revealed that treatment with LMN enhanced hepatoprotection, demonstrating predominantly mild, reversible lesions and suggesting a synergistic antioxidant and immunomodulatory effect. Conclusions: It could be concluded that LMN provided superior hepatoprotection compared to M or LN. These findings establish LMN as a promising bio-based nanotherapeutic agent for mitigating drug-induced hepatotoxicity through coordinated antioxidant and anti-inflammatory mechanisms.<\/jats:p>","DOI":"10.3390\/ph19010071","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T17:24:58Z","timestamp":1767201898000},"page":"71","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ameliorated Hepatoprotective Aptitude of Novel Lignin Nanoparticles on APAP-Induced Hepatotoxicity in a Murine Model"],"prefix":"10.3390","volume":"19","author":[{"given":"Monika","family":"Toneva","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Animal Physiology, Biochemistry and Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikola","family":"Kostadinov","sequence":"additional","affiliation":[{"name":"Department of General and Clinical Pathology, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhani","family":"Yanev","sequence":"additional","affiliation":[{"name":"Faculty of Industrial Technology, Technical University of Sofia, 1756 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galina","family":"Nikolova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanka","family":"Karamalakova","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Faculty of Medicine, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1306-0905","authenticated-orcid":false,"given":"Milena","family":"Tzanova","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Faculty of Agriculture, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8159-4530","authenticated-orcid":false,"given":"Zvezdelina","family":"Yaneva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Animal Physiology, Biochemistry and Chemistry, Faculty of Veterinary Medicine, Trakia University, 6000 Stara Zagora, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liao, J., Lu, Q., Li, Z., Li, J., Zhao, Q., and Li, J. 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