Choline deficient diet

Chemiluminescence has been used to demonstrate increased free-radical activity after induction of caerulein pancreatitis, with levels peaking at about 20 min and decreasing rapidly to control values thereafter (Gough et al., 1990). Electron spin resonance has been used to demonstrate increased hydroxyl radical activity in choline-deficient diet pancreatitis in the mouse (Nonaka etal., 1989a). 

Sasaki FI, Yanai M, Meguro K, Sekizawa K, Ikarashi Y, Maruyama Y, Yamamoto M, Matsuzaki Y, Takishima T. (1991). Nicotine improves cognitive disturbance in rodents fed with a choline-deficient diet. Pharmacol Biochem Behav. 138(4) 921-25. 

M.I.R. (1985) Interactions of Barbiturates and a Choline Deficient Diet in Promotion of Liver Carcinogenesis. This Volume. 

Polychlorinated (brominated) Choline-deficient diet biphenyl(s)... 

Barbiturates, Choline-Deficient Diet, and Liver Cancer 329... 

DEHP effects on the peroxisomal system of the liver appeared to be increased in rats kept on a choline deficient diet (Perera et al. 1986). This conclusion was based on an increase in the conjugated dienes in the microsomes of choline-deficient animals exposed to 500 mg/kg DEHP for 4 weeks. Conjugated dienes are indicators of free radical oxygen modification of cellular lipids. 

Perera MI, Katyal SL, Shinozuka H. 1986. Suppression of choline-deficient diet-induced hepatocyte membrane lipid peroxidation in rats by the peroxisome proliferators 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio(N-beta-hydroxyethyl)acetamide and di(2-ethylhcxyl)phthalate. Cancer Res 46 3304-3308. 

Other studies in animal models show that a choline-deficient diet promotes liver carcinogenesis (256-261). In fact, choline is the only known nutrient for which deficiency is directly linked to liver cancer in the absence of any known carcinogen (262, 263). Choline deficiency is therefore considered to have both cancer initiating and cancer promoting activities. 

Induction of acute hemorrhagic pancreatitis has a 100% mortality rate in young female mice when fed with a choline-deficient diet containing 0.5% ethio-nine. However, neither mortality nor pancreatitis was reported when ethionine was eliminated from the diet. 

From 1952 to 1962, several experimental studies using rats fed a choline-deficient diet reported the development of aortic arteriosclerosis.171-173 Using rats fed a choline-deficient diet, Sidransky et al.174 reported that elevated (2%) dietary tryptophan affected the elevated serum lipid levels of rats fed the choline-deficient diet for 1 week. Within 1 week the added dietary tryptophan to the choline-deficient diet caused a return in serum cholesterol, HDL cholesterol, and triglyceride values to levels present in rats fed the choline-supplemented diet. The significance of the alterations in serum lipids due to added dietary tryptophan was unknown, but it stressed that a specific amino acid (L-tryptophan) excess created a further nutritional imbalance, which could influence the altered circulating serum lipids due to choline deficiency. The alterations in serum lipid due to choline deficiency were thought to influence the development of arteriosclerosis in the rat, and possibly the added dietary tryptophan was able to prevent the effect. Further experimental studies are needed to determine whether this speculation was valid. 

Rats fed a choline-deficient diet rapidly develop a fatty liver. It was of interest to investigate whether rats fed such a choline-deficient diet would respond to treatment with L-tryptophan. Rats fed the control (choline-supplemented) diet but not the choline-deficient diet for 1 week and tube-fed L-tryptophan 10 min before being killed revealed enhanced labeled hepatic nuclear RNA release in vitro.174 When rats were fed elevated L-tryptophan (2%) in the diets (choline-deficient (CD) or choline-supplemented (CS)) for 1 week, labeled hepatic nuclear RNA release was increased with the CS + tryptophan diet but not with the CS + tryptophan diet groups. 3H-tryptophan binding to hepatic nuclei in vitro revealed no change in the CS + tryptophan group,... 

Chen, S.-H., Estes, L. W., and Lombardi, B., Lecitin depletion in hepatic microsomal membranes of rats fed a choline-deficient diet, Exp. Mol. Pathol., 17, 176, 1972. 

Gupta, C., Hattori, A., Betschart, J. M., Virji, M. S., and Shinozuka, H., Modulation of epidermal growth factor receptors in rat hepatocytes by two liver tumor-promoting regimens, a choline-deficient diet and a phenobarbital diet, Cancer Res., 48, 1162, 1988. 

Takahashi, S., Lombardi, B., and Shinozuka, H., Progression of carcinogen-induced foci of gamma-glutamyltranspeptidase-positive hepatocytes to hepatomas in rats fed a choline-deficient diet, Int. ]. Cancer, 29, 445, 1982. 

Decreased Complex I activity in fatty liver mitochondria isolated from rats fed with a choline-deficient diet to model in animals nonalcoholic fatty liver disease could also be completely restored to the level of control livers by exogenously added CL (Petrosillo et al., 2007). Under conditions of a choline-deficient diet the mitochondrial content of CL decreased due to reactive oxygen species-induced CL oxidation. Although no high-resolution crystal structure of the entire Complex I is available, these findings strongly suggest the presence of functionally important CL molecules in the complex. 

In an extensive series of studies. Van Deenen and co-workers (45) were able to highly label the phosphatidylcholine of red blood cell, liver mlcrosome and sarcoplasmic reticulum membranes of rats fed a choline deficient diet supplemented with [Mes- C] choline for a period of eight days. nmr studies of the... 

The fatty infiltration of the liver which accompanies the ingestion of orotic acid does not seem to be accompanied by serious pathological disturbances [293] and is readily reversible, unlike the development of fatty liver induced by a choline deficient diet. Supplementation of the orotic acid diet with adenine essentially modifies the effect of orotic acid [294]. Since PRPP is required for both the synthesis of purines and the metabolism of orotic acid, the decrease in the pool of adenine nucleotides is caused [295,296] by an inhibition of purine synthesis de novo due to extensive depletion of PRPP during the conversion of orotic acid to UMP. After the disappearance of orotic acid from the liver of animals previously fed a diet containing orotic acid, stimulation of the synthesis of adenine nucleotides occurred. 

Studies in experimental species demonstrate that methyl donor availability affects the methylation of iAs. In mice exposed to arsenite (As ), depletion of the intracellular pool of 5-adomet by treatment with periodate-oxidized adenosine (PAD), an inhibitor of 5-adomet synthesis (Hoffman 1980), results in reduced urinary excretion of DMA (Marafante and Vahter 1984). Marafante and Vahter (1986) showed that consumption of choline-deficient diet decreased the urinary excretion of DMA and increased tissue As retention in rabbits given 0.4mg arsenate (As )/kg i.v. The same effect of a diet deficient in choline, methionine, and protein was observed in rabbits after administration of 0.4mg As Vkg i.v. (Vahter and Marafante 1987). 

Fig. 19. Cortex of kidney from a weanling rat on a choline-deficient diet for 8 days. Increased thickening of capsule and a focus of necrotic tubules beneath capsule.

As an illustration of the effects of a cold environment the results of Sellers and You (1956) will be mentioned. Rats on a choline-deficient diet had fewer cardiovascular lesions if kept in the cold (1-3 C.) than did a control group living at a normal room temperature, whereas for the choline-supplemented groups the reverse was true. In this connection Client (1950) found an increase of the iodine number of the body fat in rats on exposure to a temperature of 10° instead of 20° C. This might be due to oleic acid, which can be produced in the body, rather than necessarily to the essential polyunsaturated fatty acids. 

Bruni, C., and Hegsted, D. M., 1970, Effects of choline-deficient diets on the rat hepato-cyte. Am. J. Pathol. 61 413. 

---