Solanum nigrum L. extract inhibits 2-acetylaminofluorene-induced hepatocarcinogenesis through overexpression of glutathione S-transferase and antioxidant enzymes.
Solanum nigrum L. (SN) is a widespread plant and is regarded as a common relish in the east and the south of Taiwan. Our previous study has found that SN water extract (SNWE) alleviated carbon tetrachloride-induced liver damage in rats. However, the effects of SNWE on chemical-induced hepatic injury and hepatocarcinogenesis remain unclear. Therefore, this study aims to investigate the effects of SNWE on hepatic injury and hepatocarcinogenesis by using 2-acetylaminofluorene (AAF) and AAF/NaNO(2) treatment. The serum biomarkers for hepatic injury, glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, and gamma-glutamyl transferase, and for hepatocarcinogenesis, alpha-fetoprotein, were determined. Our results showed that AAF treatment led to a significant decrease of body weight and an increase of liver/body weight and serum biomarkers for hepatic injury and hepatocarcinogenesis. Interestingly, the SNWE supplement significantly lowered the liver/body weight and the biomarkers but did not affect the body weight. Further investigation revealed that a SNWE supplement increased the expression of glutathione S-transferase-alpha and -mu, the level of transcription factor for protection from oxidative stress, Nrf2, and the level of downstream targets regulated by Nrf2, including glutathione peroxidase, superoxide dismutase-1, and catalase. Moreover, the effects of SNWE on AAF/NaNO(2)-induced hepatoma were also investigated, and the findings revealed that SNWE suppressed the progression of the hepatoma and resulted in a great increase of the survival rate. Our findings indicate that the SNWE supplement significantly alleviated the AAF-induced hepatic injury and early hepatocarcinogenesis as well as the AAF/NaNO(2)-induced lethal hepatoma, which may result from the overexpression of glutathione S-transferases, Nrf2, and antioxidant enzymes.
Hsu
Jeng-Dong
JD
Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
Kao
Shao-Hsuan
SH
Tu
Chang-Che
CC
Li
Yi-Ju
YJ
Wang
Chau-Jong
CJ
D015073:2-Acetylaminofluorene; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000517:prevention & control; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology* / Q000517:prevention & control*; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012977:Sodium Nitrite; D032324:Solanum nigrum / Q000737:chemistry*
D000975:Antioxidants; D015415:Biomarkers; D010936:Plant Extracts; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase; D012977:Sodium Nitrite