Liver injury attenuation by curcumin in a rat NASH model: an Nrf2 activation-mediated effect?
OBJECTIVE
Nuclear factor-erythroid 2-related factor-2 (Nrf2) acts as a defense system in the development of nonalcoholic steatohepatitis (NASH). Curcumin is a phenolic compound with lipid regulatory, anti-oxidative, anti-inflammatory and anti-tumorigenic properties that is beneficial in defending against NASH and was recently proved to be an Nrf2 activator. The aim of this study was to evaluate whether Nrf2 activation could be involved in NASH mitigation by curcumin.


METHODS
Hepatic, metabolic, and inflammatory parameters, along with hepatic Nrf2 protein expression were explored in adult Sprague-Dawley rats developing high-fat-diet-induced NASH and submitted to curcumin gavage for 6 weeks.


RESULTS
Curcumin administration led to lower degrees of hepatic steatosis and inflammation; lower levels of serum aminotransferases, lipids, and homeostasis model assessment of insulin resistance; and lower serum and hepatic contents of tumor necrosis factor-α (TNF-α), interleukin-6, and malondialdehyde. In contrast, higher hepatic contents of glutathione, heme oxygenase-1 and superoxide dismutase were observed in rats with curcumin. Moreover, Nrf2 expression in liver cell nuclei was significantly higher in rats with curcumin.


CONCLUSIONS
Curcumin can prevent and ameliorate NASH via lipid reduction, improve insulin resistance, improve anti-inflammatory, and have antioxidant effects, possibly related to its activation of Nrf2.
Department of Gastroenterology, Jiaxing Second Hospital, 1518 North Ring Road, Jiaxing, 314000, Zhejiang, People's Republic of China.
B
B
Li
Department of Gastroenterology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai, 200233, People's Republic of China. wanglgly@163.com.
L
L
Wang
Department of Gastroenterology, Jiaxing Second Hospital, 1518 North Ring Road, Jiaxing, 314000, Zhejiang, People's Republic of China.
Q
Q
Lu
Department of Gastroenterology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University, 600 Yi Shan Road, Shanghai, 200233, People's Republic of China.
W
W
Da
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003474:Curcumin / Q000494:pharmacology*; D059305:Diet, High-Fat; D005234:Fatty Liver; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D003474:Curcumin
Curcumin; Inflammation; Nonalcoholic steatohepatitis; Nuclear factor-erythroid 2-related factor-2; Oxidative stress; Rats