Amelioration of doxorubicin-induced myocardial oxidative stress and immunosuppression by grape seed proanthocyanidins in tumour-bearing mice.
We have investigated the protective effects of grape seed proanthocyanidins on doxorubicin-induced toxicity in tumour-bearing mice. The intraperitoneal administration of doxorubicin (2 mg kg(-1) every other day, cumulative dosage for 18 mg kg(-1)) significantly inhibited the growth of sarcoma 180, and induced myocardial oxidative stress with decreased superoxide dismutase and glutathione peroxidase activity while increasing malondialdehyde formation in the heart or serum. Doxorubicin-induced myocardial oxidative stress also reduced lactate dehydrogenase and creatine kinase activity in the heart and elevated their levels in the serum. Doxorubicin also affected immune functions of tumour-bearing mice with significantly decreased interleukin-2 (IL-2) and interferon-gamma (INF-gamma) production, and slightly decreased natural killer (NK) cell cytotoxicity, lymphocyte proliferation and CD4+/CD8+ ratio. It markedly increased the percentages of cytotoxic T cells (CD3+CD8+), helper T cells (CD3+CD4+), IL-2R+CD4+, and IL-2R+ cells as compared with untreated tumour-bearing mice. The intragastric administration of proanthocyanidin (200 mg kg(-1) daily) significantly inhibited tumour growth, and increased NK cell cytotoxicity, lymphocyte proliferation, CD4+/CD8+ ratio, IL-2 and INF-gamma production. Moreover, proanthocyanidin strongly enhanced the anti-tumour effect of doxorubicin and the above immune responses, and completely eliminated myocardial oxidative stress induced by doxorubicin. In conclusion, intragastric administration of proanthocyanidin could enhance the anti-tumour activity of doxorubicin and ameliorate doxorubicin-induced myocardial oxidative stress and immunosuppression in tumour-bearing mice.
Zhang
Xiao-Yu
XY
Department of Physiology, College of Basic Medicine, Lanzhou University, Lanzhou 730 000, People's Republic of China. zhangxiaoyuly@yahoo.com
Li
Wen-Guang
WG
Wu
Yong-Jie
YJ
Gao
Ming-Tang
MT
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D015703:Antigens, CD / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004347:Drug Interactions; D005260:Female; D006321:Heart / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D016131:Lymphocyte Subsets / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D012510:Sarcoma 180 / Q000188:drug therapy*; D012639:Seeds; D027843:Vitis / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D015703:Antigens, CD; D000970:Antineoplastic Agents; D016207:Cytokines; D007166:Immunosuppressive Agents; D044945:Proanthocyanidins; D015375:Receptors, Interleukin-2; C013221:proanthocyanidin; D004317:Doxorubicin