GASTROENTEROLOGY 1984;86:618-26 Dietary Influences on the Hepatic Mixed- Function Oxidase System in the Rat After Portacaval Anastomosis ALAN D. PROIA, K. DAVID G. EDWARDS, DONALD J. McNAMARA, and KARL E. ANDERSON The Rockefeller University, New York. and Cornell University Medical College/Memorial Sioan- Kettering Cancer Center, New York, New York Studies were undertaken to determine the influence of diet on the hepatic mixed-function oxidase sys- tem in rats after portacaval anastomosis. Male rats fed either a cereal-based or purified diet underwent portacaval anastomosis. Weight gain after surgery was highly dependent on the diet. Because rats fed the cereal-based diet weighed 50% less at 4-5 wk after portacaval shunt surgery than unoperated con- trols fed the same diet, pair-fed unoperated controls were also studied. Rats fed the purified diet grew normally after shunting and therefore studies with this diet did not require pair-fed controls. Shunted rats fed the cereal-based diet had lower liver weights, hepatic microsomal protein concentrations, ethylmorphine N-demethylase, aniline hydroxylase, and cytochromes P 450 and b s when compared with corresponding values in un operated controls fed the same diet ad libitum; comparisons with pair-fed controls indicated that decreased intake of the cere- al-based diet could account for part but not all of the changes seen after portacaval anastomosis . It was shown in rats fed the purified diet that sham opera- Received May 17, 1983. Accepted October 26, 1983. Address requests for reprints to: Alan D. Proia, M.D., Ph.D., Department of Pathology, Duke University Medical Center, Dur- ham, North Carolina 27710. This work was supported by U.S. Public Health Service Grants HL 06222 from the National Heart, Lung and Blood Institute; FR- 00102 from the General Clinical Research Centers Branch (Divi- sion of Research Resources); General Research Support Grant 2160-191 from the National Institutes of Health; and by the Minot H. Shaw Memorial Fund (2160-558); the Brian Piccolo Fund (1160-015); a Grant-in-Aid from the National Dairy Council; grants from the Herman Goldman Foundation and Weight Watch- ers Foundation, Inc., a Career Scientist Award to Donald J. McNamara from the Irma T. Hirschi Charitable Trust, and a Research Career Development Award 1-K04-GM0030 to Karl E. Anderson from the U.S. Public Health Service. The authors thank Jeffrey C. Strachan for his excellent technical assistance and Nancy Hall for secretarial assistance. © 1984 by the American Gastroenterological Association 0016-5085/84/$3.00 tion had no effect on the mixed-function oxidase system, whereas portacaval resulted in reduced liver weight, microsomal protein, ethylmor- phine N-demethylase, aniline hydroxylase, and cy- tochrome P 450' In comparing shunted rats fed the two types of diet, in contrast with the effects of these diets in normal rats, these hepatic microsomal mixed-function oxidase system components were generally lower in the shunted rats fed the cereal diet. It is concluded that although decreased mixed- function oxidase activity occurs after portacaval anastomosis in the rat, the diet can have an addi- tional substantial influence. Dietary influences on drug oxidations may be an important consideration in drug therapy after portacaval anastomosis. The surgical procedure of portacaval anastomosis (PCA) is a common form of treatment for relieving bleeding esophageal varices in patients with portal hypertension (1) and is sometimes used to relieve hypersplenism and intractable ascites (2). More re- cently, two diseases due to inborn errors of metabo- lism, namely glycogen storage disease and homozy- gous familial hypercholesterolemia, have been ameliorated by PCA (3-5). Portacaval shunts have also been widely used in experimental animals to study the metabolic consequences of portal blood diversion past the liver (6,7); much of this research has concentrated on the pathogenesis of hepatic encephalopathy (8,9) and on the regulation of lipid metabolism (10-12). Previous studies have also demonstrated that rats with end-to-side PCA have lower activity of the hepatic microsomal mixed-function oxidase system when compared with sham-operated controls (13- 18). These observations are potentially important because the microsomal mixed-function oxidase sys- Abbreviations used in this pap e r: PCA, portacaval anastomosis.