Hepatoprotective effects of curcumin in rats after bile duct ligation via downregulation of Rac1 and NOX1.
OBJECTIVE
New evidence has proven the hepatoprotective activity of curcumin; however, its underlying mechanisms remain to be elucidated. The aim of this study was to investigate the protective effect of curcumin on hepatic damage by measuring the antioxidant capacity and expression level of Rho-related C3 botulinum toxin substrate (Rac1), Rac1-Guanosine triphosphate (Rac1-GTP), and NADPH oxidase 1(NOX1) in biliary duct-ligated (BDL)-fibrotic rat model.


METHODS
Wistar rats weighing 200 to 250 g were divided into four groups (n = 8 for each): sham group, sham+Cur group (received curcumin 100 mg/kg daily), BDL+Cur group, and BDL group. The mRNA and protein expression levels of Rac1, Rac1-GTP, and NOX1 were measured by real-time polymerase chain reaction and Western blotting, respectively.


RESULTS
Curcumin treatment of BDL rats reduced liver injury, as verified by improvement of hepatic cell histologic alterations, and by reduction of hepatic enzymes. Moreover, the increase in the expression of Rac1, Rac1-GTP, and NOX1 observed in BDL rats was precluded and reversed back toward normalcy by curcumin treatment (P < 0.05). We also observed an escalation of protein thiol groups, increased enzyme activity of serum antioxidant markers (e.g., superoxide dismutase) and a decrease of carbonylation in curcumin-treated BDL rats compared with BDL rats (P < 0.05).


CONCLUSIONS
Curcumin attenuated liver damage through the downregulation of Rac1, Rac1-GTP, and NOX1 as well as reduced oxidative stress in the serum and liver tissue of BDL rats.
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Zohreh-Al-Sadat
ZA
Ghoreshi
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Razieh
R
Kabirifar
Department of Physiology, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran.
Fatemeh
F
Safari
Department of Pharmacology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Alireza
A
Karimollah
Department of Biochemistry, School of Medicine, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran. Electronic address: Morady2008@gmail.com.
Ali
A
Moradi
Department of Biochemistry, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran.
Ebrahim
E
Eskandari-Nasab
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001652:Bile Ducts / Q000601:surgery; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008107:Liver Diseases / Q000188:drug therapy*; D008111:Liver Function Tests; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
D000975:Antioxidants; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; C000614712:NOX1 protein, rat; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D003474:Curcumin
Curcumin; Liver damage; NOX1; Rac1