REDUCTION OF GUT HYPOPLASIA AND CACHEXIA IN TUMOR-BEARING RATS MAINTAINED ON TOTAL PARENTERAL-NUTRITION AND TREATED WITH PEPTIDE YY AND CLENBUTEROL

Prevention of gut hypoplasia associated with total parenteral nutritio n (TPN) was investigated in 67 adult male Fischer 344 rats. Mass and p rotein content of the small intestine was reduced by 31% and 39%, resp ectively, after 7 d of TPN in tumor-bearing (TB) rats. Coinfusing pept ide YY (PYY; 1 nmol.kg(-1). h(-1)) and treating the rats with the anab olic beta-adrenergic agonist, clenbuterol (CLE; 2 mg.kg(-1).d(-1)), re sulted In significant savings in small intestine weight (26% increase) and protein (42% increase). Although the colon also exhibited a signi ficant decrease in mass (31%), none of the treatment combinations were effective in this region of the gut. Histologic analysis of ileum sug gested that the additive effects of PYY and CLE were due to differenti al effects of these compounds on mucosal and muscular tissues, respect ively. This combination of treatments also resulted in significant sav ings (30% increase) in gastrocnemius protein, suggesting a reduction i n the cachectic response. These results suggest that TPN-induced gut h ypoplasia and cancer cachexia may be reduced by the proper combination of nutritional, hormonal, and pharmacologic treatments, in addition, the anabolic effects of various treatments may be additive to countera ct TPN-induced gut atrophy. Nutrition 1998;14:502-507. (C)Elsevier Sci ence Inc. 1998.