Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity.
OBJECTIVE
Cyclosporine A (CsA) is an immunosuppressive drug, but cardiotoxicity is one of its side effects. Free oxygen radical damage and apoptosis are considered to be responsible for CsA-induced cardiotoxicity. Grape seed proanthocyanidin extract (GSPE) displays antioxidant and antiapoptotic activities. Therefore, we aimed to evaluate the effect of GSPE on CsA-induced cardiotoxicity.


METHODS
Twenty-four rats were divided into four groups, with six rats in each group. CsA-induced nephropathy was induced by administration of 25 mg/kg CsA. The experiment was discontinued on day 21, and total oxidant system (TOS), total antioxidant system (TAS), oxidative stress index (OSI), and malondialdehyde (MDA) were measured in order to evaluate oxidative damage to the heart tissue. In addition to cardiac histopathology, transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) was performed to determine apoptosis.


RESULTS
The CsA group showed a significant increase in TOS, OSI, MDA, cardiac histopathological score, and apoptotic index (AI); in the CsA + GSPE group, OSI, MDA, cardiac histopathological score, and AI decreased significantly, and TAS levels showed a significant increase.


CONCLUSIONS
In this study, we demonstrated for the first time in the literature that GSPE prevents CsA cardiotoxicity and that this effect can be achieved by antiapoptotic and antioxidant activities.
Department of Nephrology, School of Medicine, Karadeniz Technical University, Trabzon, Turkey. gulsumozkan78@hotmail.com
Gülsüm
G
Ozkan
Sukru
S
Ulusoy
Mehmet
M
Alkanat
Asım
A
Orem
Buket
B
Akcan
Safak
S
Ersöz
Esin
E
Yuluğ
Kubra
K
Kaynar
Sait
S
Al
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D016572:Cyclosporine / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D056604:Grape Seed Extract; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000633:toxicity; D020287:In Situ Nick-End Labeling; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins; D051381:Rats; D017207:Rats, Sprague-Dawley; D027843:Vitis
D000975:Antioxidants; D016166:Free Radical Scavengers; D056604:Grape Seed Extract; C511402:Grape Seed Proanthocyanidins; D007166:Immunosuppressive Agents; D044945:Proanthocyanidins; D016572:Cyclosporine