Naproxen, clenbuterol and insulin administration ameliorates cancer cachexia and reduce tumor growth in Walker 256 tumor-bearing rats.
Cancer cachexia is characterized by anorexia and intense peripheral catabolism. We examine the potential benefits of combination of different anabolic agents such as insulin and clenbuterol associated to prostaglandin synthesis inhibitor (naproxen) on tumor growth, cachexia and renal function in Walker 256 tumor-bearing rats (WK). Groups were separated into WK, and WK with naproxen (WK N) or naproxen plus clenbuterol (WK NCb) or naproxen plus clenbuterol plus insulin (WK NCbI). Treatment begins at the 4th day after tumor inoculation, at the 14th day they were killed, glycemia, lacticidemia, glycogen content from liver, soleus and gastrocnemius muscles, tumor mass, body weight and kidney function were determined. Glycemia and glycogen content were reduced and lacticidemia increased in WK (p<0.05) as compared to control rats. The glycogen content recovered in all treated groups. Tumor weight was significantly reduced by the different treatments. At the 14th weight change (carcass-initial body weight) in the control increased by 38% and in the WK -2%. Naproxen treatment (WK N) induced an increased by 14%. The inclusion of clenbuterol (WK NCb) and insulin (WK NCbI) by 38 and 41%, respectively. Mean glomerular filtration rate (GFR) increased in the WK (p<0.05) as compared to control, but in the WK NCb the GFR was similar to control. Our results suggest that naproxen is able to reduce tumor growth and its association with insulin and clenbuterol induce mass weight gain and recovery energy fuel.
Piffar
P M
PM
Laboratório de Metabolismo Celular, Departamento de Fisiologia, Setor de Ciências Biológicas, Universidade Federal do Paraná, Centro Politécnico, Jd. das Américas, Curitiba-Pr 81530-990, Brazil.
Fernandez
R
R
Tchaikovski
O
O
Hirabara
S M
SM
Folador
A
A
Pinto
G J
GJ
Jakobi
S
S
Gobbo-Bordon
D
D
Rohn
T V
TV
Fabrício
V E B
VE
Moretto
K D
KD
Tosta
E
E
Curi
R
R
Fernandes
L C
LC
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002100:Cachexia / Q000188:drug therapy*; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000473:pathology; D002976:Clenbuterol / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D002149:Energy Intake; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000473:pathology; D009288:Naproxen / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000318:Adrenergic beta-Agonists; D001786:Blood Glucose; D016861:Cyclooxygenase Inhibitors; D007328:Insulin; D009288:Naproxen; D006003:Glycogen; D002976:Clenbuterol