Tags

Type your tag names separated by a space and hit enter

Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver.
Int Immunopharmacol 2005; 5(9):1397-405II

Abstract

Cyclosporine A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension and hepatotoxicity. Among possible mechanisms of CsA-induced hepatic damage, oxidative stress has been suggested. Melatonin (Mel) has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of some heat shock proteins (HSP) and the Mel antioxidant properties against CsA-induced injury. Rats were divided into four groups, which were treated respectively with olive oil, Mel alone, CsA and CsA plus Mel for 30 days. At the end of the treatments, the animals were killed and hepatic tissue was treated for morphological (haematoxylin-eosin), biochemical (reduced glutathione, GSH and malondialdehyde, MDA) and immunohistochemical (HSP60, HSP72, GRP75 and MT) analyses. The results indicate that CsA-induced hepatotoxicity was characterised by morphological alterations in tissue architecture, changes in GSH and MDA levels and increase in stress protein expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that Mel plays a protective action against CsA-induced oxidative stress, as supported by biochemical and immunohistochemical results.

Authors+Show Affiliations

Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, 25123 Brescia, Italy. rezzani@med.unibs.it

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15953566

Citation

Rezzani, Rita, et al. "Protective Role of Melatonin in Cyclosporine A-induced Oxidative Stress in Rat Liver." International Immunopharmacology, vol. 5, no. 9, 2005, pp. 1397-405.
Rezzani R, Buffoli B, Rodella L, et al. Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver. Int Immunopharmacol. 2005;5(9):1397-405.
Rezzani, R., Buffoli, B., Rodella, L., Stacchiotti, A., & Bianchi, R. (2005). Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver. International Immunopharmacology, 5(9), pp. 1397-405.
Rezzani R, et al. Protective Role of Melatonin in Cyclosporine A-induced Oxidative Stress in Rat Liver. Int Immunopharmacol. 2005;5(9):1397-405. PubMed PMID: 15953566.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective role of melatonin in cyclosporine A-induced oxidative stress in rat liver. AU - Rezzani,Rita, AU - Buffoli,Barbara, AU - Rodella,Luigi, AU - Stacchiotti,Alessandra, AU - Bianchi,Rossella, PY - 2005/02/16/received PY - 2005/03/03/revised PY - 2005/03/14/accepted PY - 2005/6/15/pubmed PY - 2005/11/3/medline PY - 2005/6/15/entrez SP - 1397 EP - 405 JF - International immunopharmacology JO - Int. Immunopharmacol. VL - 5 IS - 9 N2 - Cyclosporine A (CsA) is the most widely used immunosuppressive drug for preventing graft rejection and autoimmune disease. However, the therapeutic treatment induces several side effects such as nephrotoxicity, cardiotoxicity, hypertension and hepatotoxicity. Among possible mechanisms of CsA-induced hepatic damage, oxidative stress has been suggested. Melatonin (Mel) has been successfully used as a potent antioxidant against many pathophysiological states. This experimental study was performed to test, during CsA treatment, the alterations of some heat shock proteins (HSP) and the Mel antioxidant properties against CsA-induced injury. Rats were divided into four groups, which were treated respectively with olive oil, Mel alone, CsA and CsA plus Mel for 30 days. At the end of the treatments, the animals were killed and hepatic tissue was treated for morphological (haematoxylin-eosin), biochemical (reduced glutathione, GSH and malondialdehyde, MDA) and immunohistochemical (HSP60, HSP72, GRP75 and MT) analyses. The results indicate that CsA-induced hepatotoxicity was characterised by morphological alterations in tissue architecture, changes in GSH and MDA levels and increase in stress protein expression. In conclusion, our data suggest that the imbalance between production of free oxygen radicals and antioxidant defence systems, due to CsA administration, is a mechanism responsible for oxidative stress. Moreover, we show that Mel plays a protective action against CsA-induced oxidative stress, as supported by biochemical and immunohistochemical results. SN - 1567-5769 UR - https://www.unboundmedicine.com/medline/citation/15953566/Protective_role_of_melatonin_in_cyclosporine_A_induced_oxidative_stress_in_rat_liver_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1567-5769(05)00078-0 DB - PRIME DP - Unbound Medicine ER -