Send to

Choose Destination
See comment in PubMed Commons below
Mol Med Rep. 2014 Sep;10(3):1323-8. doi: 10.3892/mmr.2014.2382. Epub 2014 Jul 15.

Melatonin synergized with cyclosporine A improves cardiac allograft survival by suppressing inflammation and apoptosis.

Author information

Department of Cardiac Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China.


Melatonin, a widespread physiological mediator, has been demonstrated to exhibit a dose‑dependent immunoregulatory effect in vitro and in vivo, including mediating physiological circadian rhythms, neutralizing free radicals and exerting antisenescence actions. In the present study, the efficacy and mechanism of melatonin alone or in combination with cyclosporine (CsA) in prolonging heart transplantation survival was examined. Daily treatment with melatonin (200 mg/kg/day) through a gavage, significantly prolonged the survival of cardiac grafts (mean survival time, 13.4±2.4 days; n=7; P<0.0001) compared with the untreated controls (5.8±1.2 days; n=7). When CsA (5 mg/kg/day) was co‑administered with melatonin (50 mg/kg/day), the survival rate improved (31.6±2.4 days; n=7; P<0.001), compared with that achieved by only 20 mg/kg/day CsA (22±2.8 days; n=7). As expected, melatonin significantly alleviated the inflammatory response and apoptosis as determined by TdT‑mediated dUTP‑biotin nick end labeling assay (P<0.05). Further analysis demonstrated that melatonin significantly reduced p65 activation and the release of inflammatory factors. Therefore, these findings indicate that melatonin in combination with CsA protected the cardiac allograft by inhibiting inflammation‑induced apoptosis. These results provide evidence for a novel therapeutic approach for future immunosuppressive agents in organ transplantation.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Spandidos Publications
    Loading ...
    Support Center