Prevention by acetylsailcylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats

Denda, Ayumi; Tang, Qing; Endoh, Takehiro; Tsujiuchi, Toshifumi; Horiguchi, Kohsuke; Noguchi, Osamu; Mizumoto, Yasushi; Nakae, Dai; Konishi, Yoichi

doi:10.1093/carcin/15.6.1279

Cited by 56 publications

(37 citation statements)

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“…This fact was clearly bom out by our previous studies (25,26) (11,12) in the CDAA diet than the CD diet (free choline: below detectable limits versus 630 pmoles/kg diet; phosphatidylcholine: 11 versus 891 1 pmoles/kg diet); and (b) although the 2 diets contain the same amount of methionine, the latter is offered as proteins in the CD diet, and as a free amino acid in the CDAA diet; any easier and greater utilization of free methionine by the intestinal flora could reduce its absorption by the rats (32,33).…”

Section: Introductionsupporting

confidence: 60%

“…In male Fischer-344 rats, this diet proved to induce the same basic spectrum of acute and chronic morphological alterations in the liver, but more rapidly and significantly more severe than the alterations induced by the CD diet, as shown for example by the development of frank cirrhosis, more numerous and larger preneoplastic lesions, and a 100% incidence of HCC, all within a 12-mo feeding period (12,25,26). In addition, the CDAA diet induced more rapid and marked oxidative damage of hepatocellular DNA, as revealed by the formation of 8-hydroxyguanine (8-OHG), than did the CD diet (25).…”

Section: Introductionmentioning

confidence: 89%

“…Recently, the resistance of female Fischer-344 rats toward induction of a high degree of compensatory mitogenesis and eventual tumorigenesis was found to be not absolute, but a function of the severity of the dietary lipotrope deficiency, because it was overcome by feeding a diet devoid of methionine, folic acid, and vitamin B12, as well as of choline (29 (12,19,(24)(25)(26)36 (16,29), (b) the nature and role of foci of enzyme-altered hepatocytes, and (c) the source and significance of Differences in methodological approaches preclude an exact comparison of the degree of cell proliferation induced by the CDAA diet in female rats (Fig. 5), and the degrees induced by the CD diet in males (16), or by a severe lipotrope-deficient diet in females (29).…”

Section: Introductionmentioning

confidence: 99%

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Comparative Changes in the Liver of Female Fischer-344 Rats after Short-Term Feeding of a Semipurified or a Semisynthetic L-Amino Acid-Defined Choline-Deficient Diet

et al. 1995

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Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD) diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the CD diet. Greater elevations in serum aspartate and alanine aminotransferase activities were also present in the former rats, along with higher 2-bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8-hydroxyguanine were detected in liver DNA, but were not significantly different in rats fed the 2 diets, or from those present in a group of control rats killed at 0 time. Glutathione S-transferase placental formpositive focal lesions were not observed in any of the rats. The results show that the CDAA diet causes more severe degrees of steatosis and liver cell death and proliferation than the CD diet, raising the possibility that it may, in contrast to the CD diet, result in the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.

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Section: Introductionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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Comparative Changes in the Liver of Female Fischer-344 Rats after Short-Term Feeding of a Semipurified or a Semisynthetic L-Amino Acid-Defined Choline-Deficient Diet

et al. 1995

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“…Evidence from animal models Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects [59][60][61][62][63][64] . In the rat model of choline-deficient, L-amino acid-defined diet (CDAA)-induced hepatocarcinogenesis the administration of aspirin or nimesulide with the diet decreased the number of preneoplastic and neoplastic nodules [60,63] .…”

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 99%

“…In the rat model of choline-deficient, L-amino acid-defined diet (CDAA)-induced hepatocarcinogenesis the administration of aspirin or nimesulide with the diet decreased the number of preneoplastic and neoplastic nodules [60,63] . In a recent study by Marquez-Rosado [64] treatment with celecoxib was highly effective in inhibiting the multiplicity and size of liver preneoplastic lesions induced by DEN, 2-AAF and partial hepatectomy.…”

Section: Cox Inhibitors In Hepatocellular Carcinomamentioning

confidence: 99%

Cyclooxygenases in hepatocellular carcinoma

Cervello¹,

Montalto²

2006

WJG

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M a n y e p i d e m i o l o g i c a l s t u d i e s d e m o n s t r a t e t h a t treatment with non-steroidal anti-inflammatory drugs(NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs nonselectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by proinflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, m a l i g n a n t , a n d m e t a s t a s t i c c a n c e r s , i n c l u d i n g hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in welldifferentiated HCCs compared with less-differentiated H C C s o r h i s t o l o g i c a l l y n o r m a l l i v e r , s u g g e s t i n g that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC.In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor cells.The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood.Increasing evidence suggests the involvement of molecular targets other than COX-2 in the antiproliferative effects of COX-2 selective inhibitors. Therefore, COX-inhibitors may use both COX-2-dependent and COX-2-independent mechanisms to mediate their antitumor properties, although their relative contributions toward the in vivo effects remain less clear.Here we review the features of COX enzymes, t h e r o l e o f t h e e x p r e s s i o n o f C O X i s o f o r m s i n hepatocarcinogenesis and the mechanisms by which they may contribute to HCC growth, the pharmacological properties of COX-2 selective inhibitors, the antitumor effects of COX inhibitors, and the rationale and feasibility of COX-2 inhibitors for the treatment of HCC.

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The Effects of Acetylsalicylic Acid, Interferon‐α, and Vitamin E on Prevention of Parenteral Nutrition‐Associated Cholestasis: An Experimental Study

Demircan,

Uguralp,

Mutus

et al. 1999

J. pediatr. gastroenterol. nutr.

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Background:Cholestasis is one of the major complications of parenteral nutrition. The purpose of this experimental study was to detect the effects of acetylsalicylic acid (ASA), vitamin E (Vit E), and interferon‐α (IFN‐α) on prevention of parenteral nutrition‐associated cholestasis.Methods:Ten experimental groups, each consisting of 10 4‐week‐old Wistar albino rats, were formed: control 10‐ and 20‐day groups (C10 and C20), parenteral nutrition‐only 10‐ and 20‐day groups (T10 and T20), ASA‐supplemented parenteral nutrition 10‐ and 20‐day groups (TA10 and TA20), Vit E‐supplemented parenteral nutrition 10‐ and 20‐day groups (TE10 and TE20), and IFN‐α‐supplemented 10‐ and 20‐day groups (TF10 and TF20). Acetylsalicylic acid, Vit E, and IFN‐α were administered in the parenteral nutrition solution through an intraperitoneal route. At the end of the study, serum total bile acids, serum aspartate and alanine aminostransferases, and alkaline phosphatase were measured biochemically. In addition, the histopathologic findings of cholestasis were evaluated by using a morphologic portal inflammation index.Results:Although the difference in the serum levels of transferases and alkaline phosphatase was not significant among all groups (p > 0.05), it was significant in total bile acid levels (p < 0.05). There was also a significant correlation between the histopathologic changes of the liver and serum total bile acid concentrations (p < 0.05). Portal inflammation in varying degrees was seen in all experimental groups, but not in the control groups. Serum total bile acid concentrations in parenteral nutrition groups receiving ASA were significantly lower than those in the parenteral nutrition‐only group (p < 0.01). Although Vit E‐supplemented parenteral nutrition was effective in preventing the development of cholestasis in the 10‐day group (p < 0.05), it was not effective in the 20‐day group when compared with incidence of cholestasis in the parenteral nutrition‐only group (p > 0.05). Conversely, IFN‐α‐supplemented parenteral nutrition had no effect on cholestasis in the 10‐day group (p > 0.05) but lowered cholestasis in the 20‐day group when compared with incidence the parenteral nutrition‐only group (p < 0.05).Conclusion:Our results indicate that acetylsalicylic acid may be beneficial in preventing, and α‐interferon in treating, parenteral nutrition‐associated cholestasis.

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Prevention by acetylsailcylic acid of liver cirrhosis and carcinogenesis as well as generations of 8-hydroxydeoxyguanosine and thiobarbituric acid-reactive substances caused by a choline-deficient, L-amino acid-defined diet in rats

Cited by 56 publications

References 0 publications

Comparative Changes in the Liver of Female Fischer-344 Rats after Short-Term Feeding of a Semipurified or a Semisynthetic L-Amino Acid-Defined Choline-Deficient Diet

Comparative Changes in the Liver of Female Fischer-344 Rats after Short-Term Feeding of a Semipurified or a Semisynthetic L-Amino Acid-Defined Choline-Deficient Diet

Cyclooxygenases in hepatocellular carcinoma

The Effects of Acetylsalicylic Acid, Interferon‐α, and Vitamin E on Prevention of Parenteral Nutrition‐Associated Cholestasis: An Experimental Study

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