Evaluation of the protective effect of losartan in acetaminophen-induced liver and kidney damage in mice

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 2024-07, Vol.397 (7), p.5067-5078
• Main Authors: Şahin, Serkan, Aydın, Ayça Çakmak, Göçmen, Ayşe Yeşim, Kaymak, Emin
• Format: Article
• Language: English
• Subjects: Acetaminophen; Acetaminophen - toxicity; Analgesics; Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Biomedical and Life Sciences; Biomedicine; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - prevention & control; Creatinine; Cytokines - metabolism; Hepatotoxicity; IL-1β; Inflammation; Injection; Interleukin 10; Interleukin 17; Interleukin 6; Interleukin 8; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney Diseases - chemically induced; Kidney Diseases - metabolism; Kidney Diseases - pathology; Kidney Diseases - prevention & control; Kidneys; Light effects; Liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Losartan - pharmacology; Male; Mice; Neurosciences; Oxidative stress; Oxidative Stress - drug effects; Peroxisome proliferator-activated receptors; Pharmacology/Toxicology; Tumor necrosis factor-α
• ISSN: 0028-1298; 1432-1912; 1432-1912
• DOI: 10.1007/s00210-023-02937-0

Acetaminophen is widely used among humans as an antipyretic and analgesic. In this study, the protective effect of losartan in hepatotoxicity and nephrotoxicity induced by acetaminophen in mice was investigated owing to its anti-inflammatory and antioxidant effects. An injection of a single dose of 500 mg/kg (i.p.) acetaminophen was administered to induce hepatotoxicity and nephrotoxicity in Groups VI–X. Losartan at doses of 1 mg/kg (Group VII), 3 mg/kg (Group VIII), and 10 mg/kg (Groups III, V, IX, and X) was injected intraperitoneally twice, at 1 and 12 h after the acetaminophen injection. Additionally, a 4 mg/kg dose of GW9662 (peroxisome proliferator-activated receptor gamma (PPAR-γ) antagonist) was injected intraperitoneally 30 min before the losartan injections in Groups V and X. At the end of 24 h, the mice were euthanized, and blood, liver, and kidney tissue samples were collected. Levels of AST, ALT, creatinine, and oxidative stress markers including TBARS, SOD, CAT, GPx, TAS, TOS, GSH, and GSSG, along with pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-10, IL-17, and TNF-α, were measured using ELISA kits. Additionally, a histological evaluation of the tissue samples was performed. Acetaminophen causes increases in the levels of AST, ALT, creatinine, TBARS, TOS, GSSG, IL-1β, IL-6, IL-8, IL-10, IL-17, and TNF-α in serum, liver, and kidney tissue. Meanwhile, it led to a decrease in the levels of SOD, CAT, GPx, TAS, and GSH. Losartan injection reversed oxidative and inflammatory damage induced by acetaminophen. Histopathological changes in liver and kidney tissue were alleviated by losartan. The substance GW9662 increased the protective effect of losartan. In light of all the data obtained from our study, it can be said that losartan has a protective effect on liver and kidney damage induced by acetaminophen due to its antioxidant and anti-inflammatory effects. In terms of the study, losartan was found to be an alternative substance that could protect people from the harmful effects of acetaminophen.