TY - JOUR
T1 - The antioxidant and anti-inflammatory activities of caffeine effectively attenuate nonalcoholic steatohepatitis and thioacetamide-induced hepatic injury in male rats
AU - Vargas-Pozada, Eduardo E.
AU - Ramos-Tovar, Erika
AU - Acero-Hernández, Consuelo
AU - Cardoso-Lezama, Irina
AU - Galindo-Gómez, Silvia
AU - Tsutsumi, Víctor
AU - Muriel, Pablo
N1 - Publisher Copyright:
© 2023 The Author(s).
PY - 2023
Y1 - 2023
N2 - 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 steato-sis. 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.
AB - 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 steato-sis. 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.
KW - NASH
KW - Nrf2
KW - anti-inflammatory
KW - antioxidant
KW - caffeine
KW - thioacetamide
UR - http://www.scopus.com/inward/record.url?scp=85149154429&partnerID=8YFLogxK
U2 - 10.1139/cjpp-2022-0303
DO - 10.1139/cjpp-2022-0303
M3 - Artículo
C2 - 36744700
AN - SCOPUS:85149154429
SN - 0008-4212
VL - 101
SP - 147
EP - 159
JO - Canadian Journal of Physiology and Pharmacology
JF - Canadian Journal of Physiology and Pharmacology
IS - 3
ER -