Effect of fish oil supplementation for two generations on changes of lymphocyte function induced by Walker 256 cancer cachexia in rats.
Fish oil supplementation has been shown to improve the cachectic state of tumor-bearing animals and humans. Our previous study showed that fish oil supplementation (1 g per kg body weight per day) for 2 generations had anticancer and anticachetic effects in Walker 256 tumor-bearing rats as demonstrated by reduced tumor growth and body weight loss and increased food intake and survival. In this study, the effect of fish oil supplementation for 2 generations on membrane integrity, proliferation capacity, and CD4/CD8 ratio of lymphocytes isolated from mesenteric lymph nodes, spleen, and thymus of Walker 256 tumor-bearing animals was investigated. We also determined fish oil effect on plasma concentration and ex vivo production of cytokines [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-4 (IL-4), IL-6, and IL-10]. Lymphocytes from thymus of tumor-bearing rats presented lower viability, but this change was abolished by fish oil supplementation. Tumor growth increased proliferation of lymphocytes from all lymphoid organs, and fish oil supplementation abolished this effect. Ex vivo production of TNF-alpha and IL-6 was reduced in supplemented animals, but IL-4 and IL-10 secretion was stimulated in both nontumor and tumor-bearing rats. IL-10 and IFN-gamma plasma levels was also decreased in supplemented animals. These results suggest that the anticachetic effects of fish oil supplementation for a long period of time (2 generations) in Walker 256 tumor-bearing rats may be associated to a decrease in lymphocyte function as demonstrated by reduced viability, proliferation capacity, and cytokine production.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
Alessandra
A
Folador
Thais Martins
TM
de Lima-Salgado
Sandro Massao
SM
Hirabara
Júlia
J
Aikawa
Ricardo K
RK
Yamazaki
Edgair F
EF
Martins
Heloisa Helena P
HH
de Oliveira
Nathalia
N
Pizatto
Carla C
CC
Kanunfre
Carmem M
CM
Peres
Luiz C
LC
Fernandes
Rui
R
Curi
D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D002100:Cachexia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D002279:Carcinoma 256, Walker / Q000150:complications* / Q000276:immunology / Q000401:mortality / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000276:immunology; D008214:Lymphocytes / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000378:metabolism; D015431:Weight Loss
D016588:Anticarcinogenic Agents; D016207:Cytokines; D005395:Fish Oils