Tags

Type your tag names separated by a space and hit enter

The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats.
Food Chem Toxicol. 2014 Jan; 63:174-85.FC

Abstract

This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation.

Authors+Show Affiliations

College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.College of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.Natural Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 363-883, Republic of Korea. Electronic address: dvmmk79@gmail.com.College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea. Electronic address: toxkim@jnu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24246655

Citation

Lee, In-Chul, et al. "The Involvement of Nrf2 in the Protective Effects of Diallyl Disulfide On Carbon Tetrachloride-induced Hepatic Oxidative Damage and Inflammatory Response in Rats." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 63, 2014, pp. 174-85.
Lee IC, Kim SH, Baek HS, et al. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol. 2014;63:174-85.
Lee, I. C., Kim, S. H., Baek, H. S., Moon, C., Kang, S. S., Kim, S. H., Kim, Y. B., Shin, I. S., & Kim, J. C. (2014). The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 63, 174-85. https://doi.org/10.1016/j.fct.2013.11.006
Lee IC, et al. The Involvement of Nrf2 in the Protective Effects of Diallyl Disulfide On Carbon Tetrachloride-induced Hepatic Oxidative Damage and Inflammatory Response in Rats. Food Chem Toxicol. 2014;63:174-85. PubMed PMID: 24246655.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. AU - Lee,In-Chul, AU - Kim,Sung-Hwan, AU - Baek,Hyung-Seon, AU - Moon,Changjong, AU - Kang,Seong-Soo, AU - Kim,Sung-Ho, AU - Kim,Yun-Bae, AU - Shin,In-Sik, AU - Kim,Jong-Choon, Y1 - 2013/11/15/ PY - 2013/10/11/received PY - 2013/10/24/revised PY - 2013/11/06/accepted PY - 2013/11/20/entrez PY - 2013/11/20/pubmed PY - 2014/9/23/medline KW - ALT KW - ANOVA KW - ARE KW - AST KW - Bax KW - Bcl-2-associated X KW - CCl(4) KW - CYPs KW - Carbon tetrachloride KW - Cox-2 KW - DADS KW - Diallyl disulfide KW - GAPDH KW - GPx KW - GR KW - GSH KW - GSTα KW - H&E KW - HO-1 KW - Hepatotoxicity KW - I kappaB alpha KW - IKK KW - IL-1β KW - IL-6 KW - IκB kinase KW - IκBα KW - Keap1 KW - Kelch like-ECH-associated protein 1 KW - MDA KW - NAD(P)H quinine oxidoreductase KW - NF-κB KW - NQO1 KW - Nrf2 KW - Nuclear factor E2-related factor 2 KW - Nuclear factor kappaB KW - ROS KW - RT-PCR KW - SOD KW - TNF-α KW - TUNEL KW - Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling KW - alanine aminotransferase KW - analysis of variance KW - antioxidant response element KW - aspartate aminotransferase KW - carbon tetrachloride KW - cyclooxygenase-2 KW - cytochrome P450 isoenzymes KW - diallyl disulfide KW - glutathione S-transferase alpha KW - glutathione peroxidase KW - glutathione reductase KW - glyceraldehydes-3-phosphate dehydrogenase KW - hematoxylin and eosin KW - heme oxygenase-1 KW - iNOS KW - inducible nitric oxide synthase KW - interleukin-1β KW - interleukin-6 KW - malondialdehyde KW - nuclear factor E2-related factor 2 KW - nuclear factor-kappaB KW - p-IκBα KW - phosphor-I kappa B alpha KW - reactive oxygen species KW - real-time polymerase chain reaction KW - reduced glutathione KW - superoxide dismutase KW - tumor necrosis factor-alpha SP - 174 EP - 85 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem Toxicol VL - 63 N2 - This study investigated the potential effect of diallyl disulfide (DADS) against carbon tetrachloride (CCl4)-induced oxidative hepatic damage and inflammatory response in rat liver. DADS at doses of 50 and 100 mg/kg/day was administered orally once daily for 5 days, prior to CCl4 administration. Pretreatment with DADS attenuated CCl4-induced elevated serum transaminase activities and histopathological alterations in liver. It prevented the hepatocellular apoptotic changes with induction of Bcl-2-associated X (Bax), cytochrome c, and caspase-3 caused by CCl4. An increase in the nuclear translocation of nuclear factor-kappaB (NF-κB) and phosphorylation of I kappaB alpha (IκBα) was observed in the livers of CCl4-treated rats that coincided with induction of inflammatory mediators or cytokines. In contrast, DADS inhibited NF-κB translocation and IκBα phosphorylation, and that subsequently decreased inflammatory mediators. Furthermore, DADS prevented CCl4-induced depletion of cytosolic nuclear factor E2-related factor 2 (Nrf2) and suppression of nuclear translocation of Nrf2, which, in turn, up-regulated phase II/antioxidant enzyme activities. Taken together, these results demonstrate that DADS increases the expression of phase II/antioxidant enzymes and simultaneously decreases the expression of inflammatory mediators in CCl4-induced liver injury. These findings indicate that DADS induces antioxidant defense mechanism by activating Nrf2 pathway and reduces inflammatory response by inhibiting NF-κB activation. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/24246655/The_involvement_of_Nrf2_in_the_protective_effects_of_diallyl_disulfide_on_carbon_tetrachloride_induced_hepatic_oxidative_damage_and_inflammatory_response_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(13)00751-5 DB - PRIME DP - Unbound Medicine ER -