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Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage.
J Pineal Res. 2009 Apr; 46(3):255-61.JP

Abstract

Melatonin is a potent antioxidant molecule with a capacity to protect tissues from damage caused by oxidative stress. It reduces cyclosporine A (CsA)-induced cardiotoxicity; this improvement required melatonin's binding to its membrane receptors. This experimental study examined whether melatonin is a useful tool for counteracting CsA-induced apoptosis in the heart of rats. We investigated melatonin's antiapoptotic efficacy in protecting the heart and tested whether this effect was totally dependent on its binding to membrane receptors or also involved radical scavenging. In some animals, solid lipid nanoparticles (SLN) as a melatonin delivery system were used. In one group of rats, melatonin (1 mg/kg/day i.p.) was given concurrently with CsA (15 mg/kg/day s.c.; CsA-MT) for 21 days. In other animals, melatonin loaded in SLN was injected with CsA (CsA-MTSLN). Oxidative stress in heart tissue was estimated using the evaluation of lipid peroxidation and the expression of the isoform of inducible nitric oxide (iNOS). The antiapoptotic effect of melatonin was evaluated using TUNEL staining and Bcl-2 protein family expression. CsA administration produced morphological and biochemical changes in the heart of rats, while melatonin reversed the changes. In particular, since the antiapoptotic melatonin's efficacy is mainly observed when it is loaded in SLN, we suggest that MT1/MT2 pathway is not sufficient for apoptosis antagonism and the additional intracellular effects may be required. Finally, we show that, (i) melatonin significantly reduces CsA cardiotoxicity acting also on apoptotic processes, and (ii) the reduction in CsA-induced cardiotoxicity is mediated mainly by its antioxidant effect.

Authors+Show Affiliations

Division of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy. rezzani@med.unibs.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19196438

Citation

Rezzani, Rita, et al. "Melatonin Delivery in Solid Lipid Nanoparticles: Prevention of Cyclosporine a Induced Cardiac Damage." Journal of Pineal Research, vol. 46, no. 3, 2009, pp. 255-61.
Rezzani R, Rodella LF, Fraschini F, et al. Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage. J Pineal Res. 2009;46(3):255-61.
Rezzani, R., Rodella, L. F., Fraschini, F., Gasco, M. R., Demartini, G., Musicanti, C., & Reiter, R. J. (2009). Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage. Journal of Pineal Research, 46(3), 255-61. https://doi.org/10.1111/j.1600-079X.2008.00651.x
Rezzani R, et al. Melatonin Delivery in Solid Lipid Nanoparticles: Prevention of Cyclosporine a Induced Cardiac Damage. J Pineal Res. 2009;46(3):255-61. PubMed PMID: 19196438.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Melatonin delivery in solid lipid nanoparticles: prevention of cyclosporine A induced cardiac damage. AU - Rezzani,Rita, AU - Rodella,Luigi Fabrizio, AU - Fraschini,Franco, AU - Gasco,Maria Rosa, AU - Demartini,Germana, AU - Musicanti,Claudia, AU - Reiter,Russel J, Y1 - 2009/01/31/ PY - 2009/2/7/entrez PY - 2009/2/7/pubmed PY - 2009/8/18/medline SP - 255 EP - 61 JF - Journal of pineal research JO - J Pineal Res VL - 46 IS - 3 N2 - Melatonin is a potent antioxidant molecule with a capacity to protect tissues from damage caused by oxidative stress. It reduces cyclosporine A (CsA)-induced cardiotoxicity; this improvement required melatonin's binding to its membrane receptors. This experimental study examined whether melatonin is a useful tool for counteracting CsA-induced apoptosis in the heart of rats. We investigated melatonin's antiapoptotic efficacy in protecting the heart and tested whether this effect was totally dependent on its binding to membrane receptors or also involved radical scavenging. In some animals, solid lipid nanoparticles (SLN) as a melatonin delivery system were used. In one group of rats, melatonin (1 mg/kg/day i.p.) was given concurrently with CsA (15 mg/kg/day s.c.; CsA-MT) for 21 days. In other animals, melatonin loaded in SLN was injected with CsA (CsA-MTSLN). Oxidative stress in heart tissue was estimated using the evaluation of lipid peroxidation and the expression of the isoform of inducible nitric oxide (iNOS). The antiapoptotic effect of melatonin was evaluated using TUNEL staining and Bcl-2 protein family expression. CsA administration produced morphological and biochemical changes in the heart of rats, while melatonin reversed the changes. In particular, since the antiapoptotic melatonin's efficacy is mainly observed when it is loaded in SLN, we suggest that MT1/MT2 pathway is not sufficient for apoptosis antagonism and the additional intracellular effects may be required. Finally, we show that, (i) melatonin significantly reduces CsA cardiotoxicity acting also on apoptotic processes, and (ii) the reduction in CsA-induced cardiotoxicity is mediated mainly by its antioxidant effect. SN - 1600-079X UR - https://www.unboundmedicine.com/medline/citation/19196438/Melatonin_delivery_in_solid_lipid_nanoparticles:_prevention_of_cyclosporine_A_induced_cardiac_damage_ L2 - https://doi.org/10.1111/j.1600-079X.2008.00651.x DB - PRIME DP - Unbound Medicine ER -