Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis

Kojima, Misaki; Masui, T.; Nemoto, Kiyomitsu; Degawa, Masakuni

doi:10.1016/j.toxlet.2004.06.010

Cited by 48 publications

(43 citation statements)

References 36 publications

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“…We and another group have previously observed that serum T-CHO levels rise approximately 50-70% in male SD and Wistar rats at 12-72 hr after LN-administration. 10,11,27) Therefore, WKY might be less sensitive to the effects of LN than SHRSP, SD and Wistar rats, and might have a genetic abnormality in some sort of cellular factor playing an important role in the generation of LN-induced hypercholesterolemia. In addition, considering the present results regarding the measurement of liver weights, it is considered that development of LN-induced hypercholesterolemia is not necessarily correlated with that of liver hyperplasia.…”

Section: Fig 1 Changes In the Liver Weights Of Wky And Shrsp After mentioning

confidence: 99%

“…Our group has been studying the mechanisms of inorganic Pb ion-induced hepatic hyperplasia and hypercholesterolemia. [10][11][12][13] As for hepatic hyperplasia, there is accumulating evidence that a single injection (100 µmol/kg body weight) of inorganic lead ion [e.g. lead nitrate (LN) and lead acetate] to rats induces liver cell proliferation and liver weight gain (hepatic hyperplasia) without accompanying signs of liver cell necrosis.…”

Section: Introductionmentioning

confidence: 99%

“…[14][15][16][17][18][19] The LN-injection to rats also increases both liver and C 2011 The Pharmaceutical Society of Japan serum total cholesterol (T-CHO) levels. [10][11][12] A single injection of LN induces hepatic expression of c-jun, c-myc, and c-Ha-ras genes, which are transcriptionally activated in response to various mitogens, and tumor necrosis factor-α gene, which has the ability to induce hepatic cell proliferation. [19][20][21][22][23][24] It is of interest how these changes play a role in Pb-induced liver hyperplasia.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, we have reported that LN-administration induces the gene expression of cholesterol synthesis enzymes, including 3-hydroxy-3-methylglutaryl CoA reductase and lanosterol 14α-demethylase [cytochrome P450 (CYP) 51], and decreased gene expression of a cholesterol metabolic enzyme, cholesterol 7α-hydroxylase (CYP7A1), in the livers of rats and mice. [10][11][12] It is easily understood that these expressional changes lead to the development of hypercholesterolemia. However, it remains unclear what sort of early changes act as a trigger of Pb-induced hepatic hyperplasia and/or cholesterol synthesis.…”

Section: Introductionmentioning

confidence: 99%

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Effects of Lead Nitrate on Liver Weight and Serum Total Cholesterol Amounts in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

Nemoto

Yasuda

Hikida

et al. 2011

JOURNAL OF HEALTH SCIENCE

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The administration of inorganic lead (Pb) ion to rats is well known to induce liver hyperplasia with liver enlargement and hypercholesterolemia. In the present study, the sensitivities of stroke-prone spontaneously hypertensive rat (SHRSP) and its normotensive control strain, Wistar-Kyoto rat (WKY), to these effects of Pb ion were estimated. Lead nitrate (LN) dissolved in a distillated water for injection was administered to male SHRSP and WKY by a single intravenous injection at a dose of 100 µmol/kg body weight. In WKY, significant increases in the liver weight were observed at 24 and 48 hr after LNadministration, while in SHRSP, no such significant increases were observed up to 48 hr later. On the other hand, increased levels of serum total cholesterol after LN-administration were significantly higher in SHRSP than in WKY at each time, although the constitutive (control) level was the opposite. The present findings suggest that there is different susceptibility between SHRSP and WKY to LN-induced liver hyperplasia and hypercholesterolemia and further indicate that development of hypercholesterolemia is not necessarily correlated with that of liver hyperplasia.

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Section: Fig 1 Changes In the Liver Weights Of Wky And Shrsp After mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Lead Nitrate on Liver Weight and Serum Total Cholesterol Amounts in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

Nemoto

Yasuda

Hikida

et al. 2011

JOURNAL OF HEALTH SCIENCE

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“…Nickel and chromium induced rise in serum TC, LDL-C, VLDL-C and TG and fall in serum HDL-C in Group III and Group V rats may be due to changes in gene expression of some hepatic enzyme like HMG-CoA reductase (hydroxyl-methyl-glutaryl-CoA), which in turn depresses LDL-receptor gene expression [25,26]. The rise in serum triglyceride is possibly due to hypoactivity of lipoprotein lipase in blood vessels which breaks up TG.…”

Section: Discussionmentioning

confidence: 99%

Effect of Garlic (Allium sativum) on Heavy Metal (Nickel II and ChromiumVI) Induced Alteration of Serum Lipid Profile in Male Albino Rats

Gupta

Das

Dhundasi

et al. 2008

IJERPH

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Abstract:We have studied the effect of simultaneous oral treatment of aqueous garlic extract (Allium sativum) on heavy metal (nickel II and chromium VI) induced changes in serum lipid profile. Nickel sulfate and potassium dichromate treated rats showed a significant increase in serum low density lipoprotein-cholesterol (LDL-C), very low density lipoprotein-cholesterol (VLDL-C) and triglyceride (TG) level as well as decrease in serum high density lipoprotein-cholesterol (HDL-C) level. Simultaneous garlic administration with nickel sulfate showed improvement in serum LDL-C, HDL-C, VLDL-C and TG level. But in case of potassium dichromate, garlic administration did not show satisfactory improvement in lipid profile except VLDL-C and TG level. The results indicate that garlic (Allium sativum) has some beneficial effect in preventing heavy metal (nickel and chromium VI) induced alteration of lipid profile.

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Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

Kojima

Degawa

2006

J. Appl. Toxicol.

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Changes in gene expression levels of hepatic sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) after a single i.v. injection of lead nitrate (LN, 100 micromol kg(-1) body weight) were examined comparatively by real time reverse transcriptase-polymerase chain reaction (RT-PCR) in male and female rats. Significant increases in the gene expression level of SREBP-2, a transcription factor for the HMGR gene, occurred at 6-12 h in male and at 24-36 h in female rats after LN-treatment. The gene expression level of HMGR, a rate-limiting enzyme for cholesterol biosynthesis, significantly increased at 3-48 h in male rats and 12-48 h in female rats. Subsequently, significant increases in the amount of hepatic total cholesterol in male and female rats were also observed at 3-48 h and 24-48 h, respectively. The present findings demonstrate that increases in gene expressions of hepatic SREBP-2 and HMGR and the amount of hepatic total cholesterol by LN occur earlier in male rats than in the females, and that increases in the gene expression level of HMGR and the amount of hepatic total cholesterol occur prior to the increase in the gene expression level of SREBP-2 in either sex of rats.

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Lead nitrate-induced development of hypercholesterolemia in rats: sterol-independent gene regulation of hepatic enzymes responsible for cholesterol homeostasis

Cited by 48 publications

References 36 publications

Effects of Lead Nitrate on Liver Weight and Serum Total Cholesterol Amounts in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

Effects of Lead Nitrate on Liver Weight and Serum Total Cholesterol Amounts in Stroke-Prone Spontaneously Hypertensive and Wistar-Kyoto Rats

Effect of Garlic (Allium sativum) on Heavy Metal (Nickel II and ChromiumVI) Induced Alteration of Serum Lipid Profile in Male Albino Rats

Gender-related difference in altered gene expression of a sterol regulatory element binding protein, SREBP-2, by lead nitrate in rats: Correlation with development of hypercholesterolemia

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