Diethylnitrosamine-induced increase in γ-glutamyltranspeptidase in rat liver: Its association with thyroid hormone deficiency and its reversal by tri-iodothyronine

Sulakhe, Susan J.; Pulga, Vivian B.; Tran, Sam T.

doi:10.1016/0020-711x(92)90341-w

Cited by 8 publications

(5 citation statements)

References 31 publications

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“…This stands in contrast to the very large increases in GT activity observed pathologically in chemical carcinogen-initiated changes in liver cells. Our studies in the rat 19,20 have shown that diethylnitrosamine-induced hepatocarcinogenesis is accompanied by a very large increase in enzyme activity and that the degree of increase from the normal state correlates with the phase of hepatocarcinogenesis, being moderately elevated (10-fold) at the early premalignant phase when lesions are microscopic and focal, much higher (>50-fold) in small visible premalignant nodules and higher yet (>100-fold) when the nodules are large and well developed. This is also true in our model of hepatic premalignancy consisting of hepatocarcinogenesis initiated by diethylnitrosamine and promoted by a choline-deficient diet, where the activity of GT was found to be increased >50-fold.…”

mentioning

confidence: 70%

“…The following were assessed in regular chow-fed and flax chow-fed rats: (i) growth curves; (ii) physical, behavioural and developmental milestones to gauge the impact on overall development; (iii) the levels of plasma glucose to assess glucose homeostasis; (iv) plasma levels of alanine aminotransferase (ALT) and -glutamyltranspeptidase (GT) which are indicators of liver damage; and (iv) the activity of the enzyme -glutamyltranspeptidase (GT) in the liver which we 19,20 and others 21,22 have shown to be markedly elevated in premalignant and malignant liver lesions.…”

Section: Introductionmentioning

confidence: 99%

“…19,20,[23][24][25] Results are expressed as nanomoles p-nitroaniline generated per ml plasma per minute (nmoles ml À1 min À1 ) for plasma, and nanomoles pnitroaniline generated per milligram protein per minute (nmoles mg À1 min À1 ) for liver fractions.…”

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confidence: 99%

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The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver γ‐glutamyltranspeptidase

Hemmings

Barker

2003

Cell Biochemistry & Function

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The effect of exposure to, followed by consumption of, 10% flax chow from the 18th day of gestation to the 86th day after birth was examined in male and female Fischer 344 rats. Growth curves of the flax chow-fed rats were identical to those of regular chow-fed rats, as were such developmental milestones as pinna development, growth of hair and eye opening. Acoustical startle and the righting reflexes, developmental behavioural indices, were also the same. Blood glucose levels were comparable in flax chow-fed and regular chow-fed rats at all stages of development, indicating that flax is without effect on glucose balance. There were no signs of toxicity in the flax chow-fed rats since their plasma levels of alanine aminotransferase and gamma-glutamyltranspeptidase (gammaGT) were the same as those of regular chow-fed rats. The activity of gammaGT displayed an increase in the livers of flax chow-fed rats after puberty, more so in the male-four-fold-than in the female-1.38-fold. This is suggestive of an estrogenic effect which implicates an effect of an estrogenic flax lignan. An hepatobeneficial effect of the flax-induced increase in liver gammaGT is discussed. In summary, dietary 10% flax chow is without long-term effect on growth, development and behaviour, is non-toxic and may be hepatoprotective.

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mentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

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The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver γ‐glutamyltranspeptidase

Hemmings

Barker

2003

Cell Biochemistry & Function

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“…We have also shown in the rat that the early premalignant phase of hepatocarcinogenesis is associated with high γGT levels and thyroid hormone deficiency. Restoration of normal thyroid hormone levels in these rats normalizes enzyme activity [39]. Thus, we proposed that the increase in the activity of γGT seen in premalignant lesions, may be a direct result of carcinogen-induced alterations in thyroid hormone status occurring early in the hepatocarcinogenic process.…”

Section: Acceleration Of Hepatocarcinogenesis In the Ratmentioning

confidence: 86%

“…It is noteworthy that this thyroid hormone deficiency may manifest itself in other functional ways, since the glucose levels are lower in the rats belonging to these two groups as well. We have previously shown that hypothyroid rats are also hypoglycemic [38,39]. Thus, thyroid hormone deficiency may be producing a cluster of changes, hepatic and non-hepatic, that are part of the emergence of the premalignant phenotype.…”

Section: Acceleration Of Hepatocarcinogenesis In the Ratmentioning

confidence: 99%

Administration of Diethylnitrosamine in the Immediate Postnatal Period Coupled with Exposure to a Choline Deficient Diet Accelerates Hepatocarcinogenesis in the Rat

Hemmings

Strickland²

2002

Cell Physiol Biochem

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The objectives of this study were to determine if the combination of: i. neonatal administration of diethylnitrosamine and ii. subsequent feeding of a choline deficient diet could accelerate hepatic premalignancy in the rat. The presence and size of premalignant nodules and the activity of the liver cancer enzyme marker g-glutamyltranspeptidase (gGT) were used as indicators of hepatic premalignancy. Three day old Fisher 344 rats were administered sc, saline or diethylnitrosamine (DENA): 100 mg/Kg. These were divided into choline sufficient (CS) and choline deficient (CD) groups with diets introduced to dams. On postnatal day 21 rats were weaned onto CS or CD diets. Rats in choline sufficient saline-injected (CS), choline sufficient DENA-injected (CS+DENA), choline deficient saline-injected (CD) and choline deficient DENA-injected (CD+DENA) groups were assessed on day 86. Livers of CS and CS+DENA rats were normal in appearance. Livers of CD rats were paler; those of CD+DENA rats contained visible, large, tan liver nodules. Identical results were observed in both sexes. Liver gGT activity was low and comparable in rats of CS and CS+DENA groups. Relative to liver homogenate gGT activity in the CS group, liver homogenate gGT was increased in the CD group: 14.5 fold in males and 18 fold in females; and further increased in the CD+DENA group: 78 fold in males and 54 fold in females. Plasma g-glutamyltranspeptidase exhibited the same trends as liver. The CD+DENA group demonstrated the largest increase in activity: 158 fold in males; 199 fold in females over that in the CS group. Male and female rats belonging to CS and CS+DENA groups were euthyroid; those in CD and CD+DENA groups were hypothyroid. Compared to hormone levels in the CS group, in the CD group, decreases in T3 were: 27% in males and 13% in females; decreases in T4 were: 29% in males and 5.6% in females. Compared to hormone levels in the CS groups, in the CD+DENA groups, decreases in T3 were: 25% in males and 18% in males; decreases in T4 were: 31% in males and 25% in females. Plasma glucose levels were comparable in rats of CS and CS+DENA groups. Relative to these levels, plasma glucose levels in rats of CD and CD+DENA groups were decreased 30% in males and females. Plasma transaminase levels were low and comparable in all groups. The protocol developed accelerated hepatocarcinogenesis in the Fischer 344 rat. In CD+DENA male and female rats, it produced, in 86 days, visible, large hyperplastic lesions displaying high levels of gGT and high levels of plasma gGT that are consistent with being at a well developed advanced premalignant stage of hepatocarcinogenesis without any sign of toxicity.

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Characterization of γ‐glutamyltranspeptidase in the liver of the frog: 1. Comparison to the rat liver enzyme

Sulakhe-Hemmings

Xing

1994

Cell Biochemistry & Function

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The characteristics of the enzyme gamma-glutamyltranspeptidase were determined in frog liver and compared to those of the rat. In Rana pipiens, tissue distribution studies indicated the order of activity to be: kidney >>> liver >> nerve > egg > lung > heart > skeletal muscle in homogenates. In the Rana pipiens relative to the Fischer 344 rat, the activity of the liver enzyme was somewhat greater (1.8-fold) and the kidney enzyme substantially less (25-fold). Frog liver gamma-glutamyltranspeptidase displayed strain-dependent differences in activity with Rana pipiens and Rana sylvatica exhibiting comparable activities and Xenopus laevis exhibiting 20-fold lower activities. No influence of sex was apparent in Rana pipiens in contrast to the sex dependent differences observed in the Fischer 344 rat: female:male = 7:1. In homogenates and plasma membrane fractions of Rana pipiens, Xenopus laevis and the Fischer 344 rat, high, and comparable relative specific activities, were observed, 8-11, coupled with protein yields of 2.2-2.5 per cent indicating the enzyme to be plasma membrane bound and associated with the sinusoidal surface of the liver cell.(ABSTRACT TRUNCATED AT 250 WORDS)

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Diethylnitrosamine-induced increase in γ-glutamyltranspeptidase in rat liver: Its association with thyroid hormone deficiency and its reversal by tri-iodothyronine

Cited by 8 publications

References 31 publications

The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver γ‐glutamyltranspeptidase

The effects of dietary flaxseed on the Fischer 344 rat: I. Development, behaviour, toxicity and the activity of liver γ‐glutamyltranspeptidase

Administration of Diethylnitrosamine in the Immediate Postnatal Period Coupled with Exposure to a Choline Deficient Diet Accelerates Hepatocarcinogenesis in the Rat

Characterization of γ‐glutamyltranspeptidase in the liver of the frog: 1. Comparison to the rat liver enzyme

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