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Effects of antioxidant agents against cyclosporine-induced hepatotoxicity.
J Surg Res 2015; 193(2):658-66JS

Abstract

BACKGROUND

To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity.

METHODS

Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol.

RESULTS

CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase.

CONCLUSIONS

UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system.

Authors+Show Affiliations

Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey. Electronic address: akbulutsami@gmail.com.Department of Histology and Embryology, Inonu University Faculty of Medicine, Malatya, Turkey.Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.Department of Anatomy, Adiyaman University Faculty of Medicine, Adiyaman, Turkey.Department of Biochemistry, Dicle University Faculty of Medicine, Diyarbakir, Turkey.Department of Biochemistry, Dicle University Faculty of Medicine, Diyarbakir, Turkey.Department of Surgery and Liver Transplant Institute, Inonu University Faculty of Medicine, Malatya, Turkey.Department of Biochemistry, Inonu University Faculty of Medicine, Malatya, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25281288

Citation

Akbulut, Sami, et al. "Effects of Antioxidant Agents Against Cyclosporine-induced Hepatotoxicity." The Journal of Surgical Research, vol. 193, no. 2, 2015, pp. 658-66.
Akbulut S, Elbe H, Eris C, et al. Effects of antioxidant agents against cyclosporine-induced hepatotoxicity. J Surg Res. 2015;193(2):658-66.
Akbulut, S., Elbe, H., Eris, C., Dogan, Z., Toprak, G., Yalcin, E., ... Turkoz, Y. (2015). Effects of antioxidant agents against cyclosporine-induced hepatotoxicity. The Journal of Surgical Research, 193(2), pp. 658-66. doi:10.1016/j.jss.2014.08.042.
Akbulut S, et al. Effects of Antioxidant Agents Against Cyclosporine-induced Hepatotoxicity. J Surg Res. 2015;193(2):658-66. PubMed PMID: 25281288.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of antioxidant agents against cyclosporine-induced hepatotoxicity. AU - Akbulut,Sami, AU - Elbe,Hulya, AU - Eris,Cengiz, AU - Dogan,Zumrut, AU - Toprak,Gulten, AU - Yalcin,Erhan, AU - Otan,Emrah, AU - Turkoz,Yusuf, Y1 - 2014/09/01/ PY - 2014/04/02/received PY - 2014/08/05/revised PY - 2014/08/27/accepted PY - 2014/10/5/entrez PY - 2014/10/5/pubmed PY - 2015/2/25/medline KW - Allopurinol KW - Antioxidant agents KW - Cyclosporine KW - Hepatotoxicity KW - Melatonin KW - Ursodeoxycholic acid SP - 658 EP - 66 JF - The Journal of surgical research JO - J. Surg. Res. VL - 193 IS - 2 N2 - BACKGROUND: To investigate the potential protective antioxidant role of ursodeoxycholic acid (UDCA), melatonin, and allopurinol treatment in cyclosporine (CsA)-induced hepatotoxicity. METHODS: Hepatotoxicity was established in Sprague-Dawley rats by daily administration of CsA. Treatment groups were additionally administered UDCA, melatonin, or allopurinol treatments. Rats that received no CsA and no treatments served as a control group. Liver samples from each group were examined by histopathologic analysis to determine the effects of CsA treatment on liver morphology. Biochemical assays were also used to determine the effect of CsA treatment on liver function, in the presence or absence of UDCA, melatonin, or allopurinol. RESULTS: CsA treatment induced hepatotoxicity, resulting in sinusoidal dilatation, congestion, infiltration, hydropic degeneration, and loss of glycogen storage in the liver. From a molecular perspective, the CsA treatment increased levels of malondialdehyde (MDA) levels, decreased levels of reduced glutathione and xanthine oxidase, and decreased activities of superoxide dismutase and catalase. The CsA treatment also resulted in decreased serum total antioxidant capacity, whereas alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin levels, and total oxidant status were increased. Treatment with UDCA, melatonin, or allopurinol reduced the CsA-induced histopathologic changes, as compared with CsA-treated samples. In addition, UDCA, melatonin, or allopurinol treatment mitigated the CsA-induced effects on glutathione and MDA levels, and on superoxide dismutase and catalase activities, as well as reduced the CsA-mediated perturbations in serum levels of total antioxidant capacity, total oxidant status, and alkaline phosphatase. CONCLUSIONS: UDCA, allopurinol, and melatonin may each help to protect against CsA-induced damage to liver tissues, possibly through effects on the antioxidant system. SN - 1095-8673 UR - https://www.unboundmedicine.com/medline/citation/25281288/Effects_of_antioxidant_agents_against_cyclosporine_induced_hepatotoxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-4804(14)00800-2 DB - PRIME DP - Unbound Medicine ER -