Evaluation of Role of Telmisartan in Combination with 5-fluorouracil in Gastric Cancer Cachexia

Abstract

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). Method:MNNDwas administered once daily by oral gavage for twoweeks, and saturated NaCl (1 ml per rat)was then given once every 3 days for 4 weeks. 5-FU (75 mg/kg, i.v.) was administered once three weeks from 7th to 22nd week. From 7th to 22nd week, telmisartan (5 mg/kg, p.o.) was also administered along with 5-FU. Result: 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 carcinomaof forestomach and reducedmuscle atrophy in tibilias anterior skeletal muscle. Conclusion: 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