Hepatic Gene Expression Response to Acute Indomethacin Exposure

LaFramboise, William A.; Bombach, Kelly L.; Pogozelski, Andrew R.; Cullen, R.F.; Muha, Noah; Lyons‐Weiler, James; Spear, Scott; Dhir, Rajiv; Guthrie, Robert D.; Magovern, James A.

doi:10.1007/bf03256457

Cited by 8 publications

(11 citation statements)

References 28 publications

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“…Although FO is a well-known lipid-lowering agent, the effect of Indo in modulating lipid metabolism has not been clearly elucidated. As for hepatic steatosis, Indo was shown to increase hepatic lipid metabolism and to prevent hepatic lipid accumulation in a mouse model of cancer ( 43 ). Our data show that Indo blunts the accumulation of CE and TG in the liver.…”

Section: Discussionmentioning

confidence: 59%

Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR −/− mice

Ganesan

Milne

Webb

et al. 2012

Journal of Lipid Research

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This article is available online at http://www.jlr.org Dyslipidemia, which is characterized by elevated cholesterol or triglycerides, is a major risk factor for coronary heart disease (as reviewed in Ref. 1 ). One of the most studied forms of dyslipidemia is familial hypercholesterolemia (FH) caused by genetic factors. Although homozygous FH is a rare condition, heterozygous FH occurs in approximately 1 in 500 people and can cause premature atherosclerotic disease (as reviewed in Ref. 2 ). Combination therapy is commonly used in clinical practice to improve hypercholesterolemia. The most commonly used combination therapy consists of statins with fi brates or niacin. However, this combination has limited additive effect on LDL cholesterol levels. Moreover, the poor tolerance of niacin and the statin-induced side effects (e.g., muscle toxicity) limit the use of this combination (as reviewed in Refs. 3 and 4 ). In addition to dyslipidemia, infl ammation by itself can lead to increased risk of coronary heart disease. Therefore, a therapeutic regimen that has the potential to reduce dyslipidemia and infl ammation would be more benefi cial in reducing cardiovascular events than treatments aimed at improving dyslipidemia alone.Fish oil (FO) containing n-3 polyunsaturated fatty acids such as eicosapentaenoic acid and docosahexaenoic acid

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Section: Discussionmentioning

confidence: 59%

Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR −/− mice

Ganesan

Milne

Webb

et al. 2012

Journal of Lipid Research

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“…Meanwhile, there is no evidence of hepatocellular hypertrophy at P21 and P60. This fi nding further suggests that indomethacin may have triggered a cell proliferation as a regenerative response (17) as confi rmed by higher liver and body weight and the liver to body weight ratios in 25 mg/kg indomethacin.…”

Section: Tab 3 Effect Of Early Postnatal Exposure To Indomethacin Omentioning

confidence: 86%

“…Many developmental effects of indomethacin have been described (17). Nagai et al revealed that administration of very low dose (1.3 mg ip) of indomethacin to male rat pups daily on postnatal days 4-13 caused an abnormal lung structure with diminished alveolar air, increased alveolar duct air, increased mean linear intercept, increased septal wall thickness and diminished the number of alveolar crests (14).…”

Section: Tab 3 Effect Of Early Postnatal Exposure To Indomethacin Omentioning

confidence: 99%

“…Many hepatic toxic effects of indomethacin were described (17), whereas the effect on liver development has received no attention. Based on the preceding, the present study investigated the hypothesis that early postnatal indomethacin infl uences liver, while liver development is ongoing.…”

Section: Introductionmentioning

confidence: 99%

“…Indomethacin, which is metabolized by the liver and undergoes extensive enterohepatic circulation, resulted in a high incidence of gastrointestinal adverse effects (17). Considering that, liver is recognized as a major organ for drug metabolism during the foetal period and after birth (18,19), it might be undergoing suppression of PGs, exhibits disturbance in the growth and developmental processes with an overlap between developmental and pathological processes.…”

Section: Introductionmentioning

confidence: 99%

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Hepatocellular and developmental influences of early postnatal indomethacin in mice

Nowrouzi¹,

Azadbakht²

2017

BLL

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OBJECTIVES: The effect of early postnatal indomethacin exposure on hepatocellular and developmental alterations in mice liver was investigated. METHODS: Pups received IP injections of 0, 25, 50 and 100 mg/kg indomethacin on P0, then killed at P21 and P60. RESULTS: Indomethacin signifi cantly suppressed body weight at P21, but liver weight signifi cantly decreased only in 25 mg/kg. In contrast, liver weight and liver to body weight ratio signifi cantly increased with increasing dose of indomethacin by P60. The restoration of liver weight was a result of proliferation, as a consequence of a signifi cant increase in the number of uni and bi-nuclear hepatocytes per fi eld in 25 mg/kg at P21 and no evidence of hepatocellular hypertrophy. Indomethacin had a dose-related decrease in number of hepatocytes as the result of hepatocellular hypertrophy confi rmed with hepatocytes presenting large cellular and nuclear size in 50 and 100 mg/kg. Moreover, proliferation contributed to the increased liver size, since bi-nuclear hepatocytes and its ratio increased at P21 at fi rst and then decreased by P60 with increasing in dose. CONCLUSION: Indomethacin has long term effect on liver development in a dose-and time-dependent manner. The hepatocytes during both the liver development and regeneration show signifi cant differences in cell and nuclear number and size (Tab. 3, Fig. 2, Ref. 48). Text in PDF www.elis.sk.

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