Evaluation of role of telmisartan in combination with 5-fluorouracil in gastric cancer cachexia.
BACKGROUND
The objective of the present study was to evaluate the effect of combination of telmisartan with 5-flourouracil (5-FU) in gastric cancer cachexia induced by administering N-methyl-N'-methyl-N-nitrosoguanidine (MNNG).


METHODS
MNND was administered once daily by oral gavage for two weeks, and saturated NaCl (1ml per rat) was then given once every 3days for 4weeks. 5-FU (75mg/kg, i.v.) was administered once three weeks from 7th to 22nd week. From 7th to 22nd week, telmisartan (5mg/kg, p.o.) was also administered along with 5-FU.


RESULTS
MNNG produced significant decrease in food intake, body weight, caused hyperglycemia, dyslipidemia, hypertension worsened hemodyanamics, increased cachexia markers and increased tumor markers like lactate dehydrogenase and γ-glutamyltransferase. MNNG also produced oxidative stress in the stomach tissue. Treatment with combination of telmisartan with 5-FU produced significant increase in food intake and body weight, controlled hyperglycemia and dyslipidemia, preserved hemodynamic function, and decreased the cachexia markers while 5-FU alone did not produce any such effects. Further, the combination of telmisartan with 5-FU significantly reduced tumor marker levels, oxidative stress and also significantly decreased the cell proliferation, apoptosis, hyperkeratosis, keratohyaline granules and invasive carcinoma of forestomach and reduced muscle atrophy in tibilias anterior skeletal muscle.


CONCLUSIONS
Our data suggests that combination of telmisartan with 5-FU treatment is beneficial in controlling cancer cachexia. Telmisartan can be used as an add-on therapy with 5-FU or other traditional chemotherapeutic agents.
Institute of Pharmacy, Nirma University, India.
Shreesha
S
Sukumaran
Apex Pharmacy, Arroyo Grande, CA, USA.
Hetal J
HJ
Patel
Institute of Pharmacy, Nirma University, India. Electronic address: drbhoomikampatel@gmail.com.
Bhoomika M
BM
Patel
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage; D001565:Benzoates / Q000008:administration & dosage; D002100:Cachexia / Q000150:complications / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage; D008297:Male; D008769:Methylnitronitrosoguanidine / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000150:complications / Q000188:drug therapy*; D000077333:Telmisartan
D001562:Benzimidazoles; D001565:Benzoates; D008769:Methylnitronitrosoguanidine; D005472:Fluorouracil; D000077333:Telmisartan
Dyslipidemia; Gastric cancer cachexia; Hyperglycemia; IL-6; Muscle atrophy