The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats

• Published in: Canadian journal of physiology and pharmacology Vol. 101; no. 3; pp. 147 - 159
• Main Authors: Vargas-Pozada, Eduardo E, Ramos-Tovar, Erika, Acero-Hernández, Consuelo, Cardoso-Lezama, Irina, Galindo-Gómez, Silvia, Tsutsumi, Víctor, Muriel, Pablo
• Format: Journal Article
• Language: English
• Published: Canada NRC Research Press 01.03.2023; Canadian Science Publishing NRC Research Press
• Subjects: 4-Hydroxynonenal; Analysis; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Anti-inflammatory drugs; Antioxidants; Antioxidants - metabolism; Antioxidants - pharmacology; Antioxidants - therapeutic use; Body weight; Caffeine; Caffeine - pharmacology; Caffeine - therapeutic use; Care and treatment; Cholesterol; Cytokines; Cytokines - metabolism; Diagnosis; Dosage and administration; Fatty liver; Glutathione; Health aspects; High cholesterol diet; High fat diet; Humans; Inflammation; Liver; Liver diseases; Male; NF-E2-Related Factor 2 - metabolism; NF-kappa B - metabolism; NF-κB protein; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; Oral administration; Oxidative Stress; Rats; Signal transduction; Steatosis; Sucrose; Thioacetamide; Thioacetamide - toxicity; Canada; thioacetamide; anti-inflammatory; antioxidant; caffeine; NASH; Nrf2
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2022-0303

The antioxidant effect of caffeine, associated with its ability to upregulate the nuclear factor-E2-related factor-2 (Nrf2)-signaling pathway, was explored as a possible mechanism for the attenuation of liver damage. Nonalcoholic steatohepatitis (NASH) was induced in rats by the administration of a high-fat, high-sucrose, high-cholesterol diet (HFSCD) for 15 weeks. Liver damage was induced in rats by intraperitoneal administration of thioacetamide (TAA) for six weeks. Caffeine was administered orally at a daily dose of 50 mg/kg body weight during the period of NASH induction to evaluate its ability to prevent disease development. Meanwhile, rats received TAA for three weeks, after which 50 mg/kg caffeine was administered daily for three weeks with TAA to evaluate its capacity to interfere with the progression of hepatic injury. HFSCD administration induced hepatic steatosis, decreased Nrf2 levels, increased oxidative stress, induced the activation of nuclear factor-κB (NF-κB), and elevated proinflammatory cytokine levels, leading to hepatic damage. TAA administration produced similar effects, excluding steatosis. Caffeine increased Nrf2 levels; attenuated oxidative stress markers, including malondialdehyde and 4-hydroxynonenal; restored normal, reduced glutathione levels; and reduced NF-κB activation, inflammatory cytokine levels, and damage. Our findings suggest that caffeine may be useful in the treatment of human liver diseases.