title: Hepatoprotective effect of juglone on dimethylnitrosamine-induced liver fibrosis and its effect on hepatic antioxidant defence and the expression levels of α-SMA and collagen III.
abstract: The present study aimed to investigate the antifibrotic effects of juglone on dimethylnitrosamine (DMN)‑induced fibrosis in rats. Juglone, which is a quinone, significantly decreased DMN‑induced rat hepatic fibrosis, which was associated with increased superoxide dismutase (SOD) activity, decreased oxidative stress and reduced levels of α‑smooth muscle actin (α‑SMA) and collagen (Col) III in the liver. Serum levels of alanine aminotransferase, aspartate aminotransferase, hyaluronic acid, laminin, type III precollagen and type IV collagen were significantly reduced by treatment with juglone. Liver fibrosis was induced in male Sprague‑Dawley rats by subcutaneous injections of DMN solution and hepatic fibrosis was assessed using Massons trichome staining. The expression levels of α‑SMA and Col III were determined using immunohistochemical techniques. The activities of SOD and malondialdehyde in liver homogenates were also determined. The results suggested that juglone augmented the antioxidative capability of the liver, possibly by stimulating the activity of SOD, which promoted the inactivation of hepatic stellate cells (HSCs) and decreased the accumulation of extracellular matrix collagen in the liver, thereby alleviating hepatic fibrosis. Silymarin was used as a positive control for liver fibrosis protection. It was hypothesized that juglone alleviates or mitigates oxidative stress‑mediated hepatic fibrosis by upregulating the expression of peroxisome proliferator‑activated receptor γ and inhibiting the activation of HSC.
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: De-Jiang
authors.initials: DJ
authors.lastname: Zhou
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Mu
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Jiang
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Shu-Mei
authors.initials: SM
authors.lastname: Zheng
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Sheng
authors.initials: S
authors.lastname: He
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Weng
authors.affiliation: Internal Medicine Department of Digestion, General Hospital of Chengdu Military Region, Chengdu, Sichuan 610083, P.R. China.
authors.forename: Wei-Zheng
authors.initials: WZ
authors.lastname: Zeng
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000199:Actins; D000975:Antioxidants; D024061:Collagen Type III; D009285:Naphthoquinones; D047495:PPAR gamma; D020011:Protective Agents; C544013:alpha-smooth muscle actin, mouse; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D004128:Dimethylnitrosamine; C005134:juglone