methylnitronitrosoguanidine and Cachexia

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).. 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.. 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.. 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.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzimidazoles; Benzoates; Cachexia; Fluorouracil; Male; Methylnitronitrosoguanidine; Rats; Rats, Wistar; Stomach Neoplasms; Telmisartan