Evaluation of Role of Telmisartan in Cardiac Cachexia

Abstract

Background and Objective Cardiac cachexia is an involuntary weight loss condition associated with congestive heart failure that leads to an disrupt between catabolic and anabolic imbalance. It is specifically associated with an unintended weight loss of 5% body weight with the typical condition of chronic heart failure. Its event predicts reduced survival, independent of pertinent factors, for example, age, ejection fraction, and heart’s physical capacity.Cardiac atrophy is a kind of catabolic remodeling brought about by a physiological reaction to chronically diminished heart workload or to complicated inflammatory disease. In inducing cardiac cachexia with doxorubicin induced heart failure inflammatory cytokine with skeletal muscle wasting plays an important role. Neurohormonal abnormalities and alterations related to immunological process are observed in the pathophysiology of cardiac muscle wasting. One of the transcription factor of nuclear family is PPAR-gamma (Peroxisome proliferator activated receptor gamma) that mainly plays a role in suppressing the RAS system thereby inhibits muscle atrophy in cachexia. PPAR-gamma is best known to be expressed in several tissues like heart and other skeletal muscle. Telmisartan is reported to have beneficial effect in cancer cachexia and used in patients of hypertension. Telmisartan maintains glucose homeostasis as in cardiac cachexia glucose levels are increased with several use of energy expenditure, however role of telmisartan in cardiac cachexia is not reported. Hence, the main objective of this investigation is to investigate the role of telmisartan as PPAR-gamma agonist in cardiac cachexia. Materials and methods Balb/c mice, male/ female at 6-8 weeks of age, weighing 25-35 gm were taken for the study and maintained under temperature (22± 2*c) that is well controlled and humidity (55±5%) and 12h/12h light-dark cycle. Standard laboratory rat food and distilled water was provided ad libitum. The mice was administered intraperitoneally (i.p) with (4mg/kg) doxorubicin in 0.9% sodium chloride solution for 1st, 3rd and 5th day animals are observed upto 8 day. After 8th day treatment was started with telmisartan for 4 weeks. Telmisartan (5mg/kg) was dissolved in 0.05 % Carboxy methyl cellulose and given orally in doxorubicin induced cardiac cachexia animals.Parameters evaluated were body mass markers, inflammatory markers, markers of carbohydrate metabolism, markers of lipid metabolism, cardiac atrophy markers, skeletal muscle wasting marker. Results Body mass markers: In the cardiac cachexia control animals, there was an decrease in body weight, food and water intake. Animals treated with telmisartan showed significant improvement in % body weight reduction, % food intake, % water intake. Carcass weight shows significant reduction in the disease control animals as compared to normal control group. In disease treatment group there is significant increase in carcass weight that shows beneficial effect of telmisartan.