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Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats.
Regul Pept. 2008 Feb 07; 146(1-3):73-9.RP

Abstract

BACKGROUND

Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines.

OBJECTIVE

The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL).

METHODS

Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples.

RESULTS

In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment.

CONCLUSION

Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction.

Authors+Show Affiliations

Marmara University, School of Medicine, Department of Physiology, Haydarpaşa, Istanbul 34668, Turkey.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17884193

Citation

Işeri, Sevgin Ozlem, et al. "Ghrelin Alleviates Biliary Obstruction-induced Chronic Hepatic Injury in Rats." Regulatory Peptides, vol. 146, no. 1-3, 2008, pp. 73-9.
Işeri SO, Sener G, Saglam B, et al. Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regul Pept. 2008;146(1-3):73-9.
Işeri, S. O., Sener, G., Saglam, B., Ercan, F., Gedik, N., & Yeğen, B. C. (2008). Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. Regulatory Peptides, 146(1-3), 73-9.
Işeri SO, et al. Ghrelin Alleviates Biliary Obstruction-induced Chronic Hepatic Injury in Rats. Regul Pept. 2008 Feb 7;146(1-3):73-9. PubMed PMID: 17884193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ghrelin alleviates biliary obstruction-induced chronic hepatic injury in rats. AU - Işeri,Sevgin Ozlem, AU - Sener,Göksel, AU - Saglam,Beyhan, AU - Ercan,Feriha, AU - Gedik,Nursal, AU - Yeğen,Berrak C, Y1 - 2007/08/24/ PY - 2007/05/03/received PY - 2007/07/25/revised PY - 2007/08/09/accepted PY - 2007/9/22/pubmed PY - 2008/5/16/medline PY - 2007/9/22/entrez SP - 73 EP - 9 JF - Regulatory peptides JO - Regul Pept VL - 146 IS - 1-3 N2 - BACKGROUND: Reactive oxygen species and oxidative stress are implicated in hepatic stellate cell activation and liver fibrosis, which are initiated by recruitment of inflammatory cells and by activation of cytokines. OBJECTIVE: The possible anti-oxidant and anti-inflammatory effects of ghrelin were evaluated in a hepatic fibrosis model in rats with bile duct ligation (BDL). METHODS: Under anesthesia, bile ducts of Sprague Dawley rats were ligated, and half of the rats were subcutaneously administered with ghrelin (10 ng/kg/day) and the rest with saline for 28 days. Sham-operated control groups were administered saline or ghrelin. On the 28th day of the study, rats were decapitated and malondialdehyde (MDA) content--an index of lipid peroxidation, and myeloperoxidase (MPO) activity--an index of neutrophil infiltration--were determined in the liver tissues. Oxidant-induced tissue fibrosis was determined by collagen contents, while the hepatic injury was analyzed microscopically. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels and lactate dehydrogenase (LDH) levels were determined to assess liver function and tissue damage, respectively. Pro-inflammatory cytokines; TNF-alpha, IL-1beta and IL-6 were also assayed in plasma samples. RESULTS: In the saline-treated BDL group, hepatic MDA levels, MPO activity and collagen content were increased (p<0.001), suggesting oxidative organ damage, as confirmed histologically. In the ghrelin-treated BDL group, however, all of the oxidant responses were reversed significantly (p<0.05-p<0.001). Serum AST, ALT, LDH levels, and cytokines were elevated in the BDL group as compared to the control group, while this increase was significantly decreased by ghrelin treatment. CONCLUSION: Owing to the anti-inflammatory and anti-oxidant effect as demonstrated in our study, it is possible to speculate that exogenously administered ghrelin may possess an antifibrotic effect against biliary obstruction-induced liver fibrosis. Thus, it seems likely that ghrelin may be of potential therapeutic value in protecting the liver fibrosis and oxidative injury due to biliary obstruction. SN - 0167-0115 UR - https://www.unboundmedicine.com/medline/citation/17884193/Ghrelin_alleviates_biliary_obstruction_induced_chronic_hepatic_injury_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-0115(07)00165-6 DB - PRIME DP - Unbound Medicine ER -