The current state of serum biomarkers of hepatotoxicity

Ozer, Josef; Ratner, Marcia H.; Shaw, Martin; Bailey, Wendy J.; Schomaker, Shelli

doi:10.1016/j.tox.2007.11.021

Cited by 1,015 publications

(690 citation statements)

References 64 publications

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“…This observation is in agreement with other findings in which the values of the various RBC and WBC parameters of oral administration of saponins isolated from A. lebbeck bark extract which were found to be comparable with those of the control group [21][22][23][24][25][26][27]. The seeds extract of A. gummifera, however, significantly increased the NEUT at 250 mg/kg as compared to the control.…”

Section: Discussionsupporting

confidence: 92%

Evaluations of Biochemical, Hematological and Histopathological Parameters of Subchronic Administration of Ethanol Extract of Albizia Gummifera Seed in Albino Wistar Rat

Debebe¹,

Afework²,

Makonnen³

et al. 2017

J Clinic Toxicol

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Albizia gummifera are plants found in Ethiopia that have different medicinal values.The objective of the present study was to evaluate the toxicological effects of sub-chronic administered hydro-ethanolic (70%) seeds extract of Albizia gummiferain albino Wistar rats. The seeds of these plants were collected from different areas of Ethiopia. They were dried and crushed to powder and macerated with hydro-alcohol and placed in orbital shaker. The extract was then filtered through Whatman filter paper No.1 and the filtrate was evaporated to dryness by Rota vapor and further concentrated by water bath at 40ºC. The extract was packed in air tight brown glass bottles and kept in a refrigerator at 4ºC. The extract was then administered to rats at different doses to determine the LD 50 of the extract and at doses of 125 mg/kg/day and 250 mg/kg/day for the sub-chronic toxicity study. The LD 50 of Albizzia gummifera were found as 4000 mg/kg and 3500 mg/kg, respectively. Statistically significant difference in body weight was observed in female rats in the 10 th week at 250 mg/kg body weight of seeds extract of Albizia gummifera administered group and in the male rats at lowest dose during the 9 th and 10 th weeks of administration period for seeds extract of Millettia ferruginea.The seeds extract of Albizia gummifera statistically decreased (p ≤ 0.05) MCHin the male rats at both doses; MCHC at both 125 mg/kg and 250 mg/kg in the female rats; and MCH in the female rats at higher dose and increased RDW-CV in the male rats at both doses. It increased NEUT at the highest dose in both females and males. The seeds extract of Millettia ferruginea decreased (p ≤ 0.05) in the MCHC and MONO of female rats at the highest doses. ALP, ALT and urea were found significant in the female rats administered with 250 mg/kg of seeds extract. While, seeds extract of Albizia gummifera increased only urea in male rats at 250 mg/kg. Some histopathological changes in liver and kidney were also observed for both plants extracts. There were inflammations, congestions and focal hepatocellular necrosis of the liver tissue. The extracts also produced atrophyof the glomeruli of the kidney. The observed changes in both of the plant seeds extract might have resulted because of the presence of some bioactive ingredients in the extract. Therefore, the active ingredients which might be responsible for toxic insult should be researched with their mechanisms of actions.

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Section: Discussionsupporting

confidence: 92%

Evaluations of Biochemical, Hematological and Histopathological Parameters of Subchronic Administration of Ethanol Extract of Albizia Gummifera Seed in Albino Wistar Rat

Debebe¹,

Afework²,

Makonnen³

et al. 2017

J Clinic Toxicol

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“…Liver damage can be measured in relation to increased levels of these enzymes in the bloodstream, and this increase may be proportional to the number of affected hepatocytes (Hall 2007, Ozer et al 2008. In the present study, the absence of alterations in the serum levels of transaminases analyzed, this confirms a reduction of hepatotoxicity caused by usnic acid, resulting from their encapsulation in PLGA-microspheres.…”

Section: Discussionsupporting

confidence: 75%

Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI) during pregnancy in Wistar rats

Marinho

Antonio

Silva

et al. 2017

An. Acad. Bras. Ciênc.

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This study aimed to evaluate the teratogenic and hepatotoxic potential of the usnic acid encapsulated into PLGA-microspheres. In total, 12 female Wistar rats in pregnancy were randomly distributed in the control group (n= 6) that received 1.0 mL of physiological solution and treatment group (n= 6) that received 25 mg/kg of encapsulated usnic acid by oral administration. All females were euthanized at day 20 of pregnancy and their fetuses were removed and analyzed. During the pregnancy was observed a reduction in weight gain. There was no difference in serum transaminases levels analyzed as well as any difference in liver weight in both groups. The histomorphometric analysis of the liver from the treatment group revealed an increase in number of hepatocytes and a decrease in nuclear area of these cells. Moreover, no alteration was observed in cell area of hepatocytes or number of Kupffer cells. The fetuses had an increase in total number of hepatocytes and a reduction in the amount of megakaryocytes. These results show the hepatotoxic potential of usnic acid during pregnancy. However, its toxicity can be minimized by encapsulation in microspheres.

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“…Many studies have been conducted to identify more reliable and sensitive early blood markers for liver injury by using various high throughput technologies such as protein mass spectrometry and gene expression arrays (3,4). These efforts have so far yielded candidates that perform no better than the existing aminotransferase-based markers.…”

mentioning

confidence: 99%

Circulating microRNAs, potential biomarkers for drug-induced liver injury

Wang

Zhang²,

Marzolf³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

1,064

957

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Drug-induced liver injury is a frequent side effect of many drugs, constitutes a significant threat to patient health and has an enormous economic impact on health care expenditures. Numerous efforts have been made to identify reliable and predictive markers to detect the early signs of drug-induced injury to the liver, one of the most vulnerable organs in the body. These studies have, however, not delivered any more informative candidates than the serum aminotransferase markers that have been available for Ϸ30 years. Using acetaminophen overdose-induced liver injury in the mouse as a model system, we have observed highly significant differences in the spectrum and levels of microRNAs in both liver tissues and in plasma between control and overdosed animals. Based on our survey of microRNA expression among normal tissues, some of the microRNAs, like messenger RNAs, display restricted tissue distributions. A number of elevated circulating microRNAs in plasma collected from acetaminophen-overdosed animals are highly expressed in the liver. We have demonstrated that specific microRNA species, such as mir-122 and mir-192, both are enriched in the liver tissue and exhibit dose-and exposure duration-dependent changes in the plasma that parallel serum aminotransferase levels and the histopathology of liver degeneration, but their changes can be detected significantly earlier. These findings suggest the potential of using specific circulating microRNAs as sensitive and informative biomarkers for drug-induced liver injury.acetaminophen overdose ͉ plasma ͉ miRNA ͉ toxicity ͉ ALT

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The current state of serum biomarkers of hepatotoxicity

Cited by 1,015 publications

References 64 publications

Evaluations of Biochemical, Hematological and Histopathological Parameters of Subchronic Administration of Ethanol Extract of Albizia Gummifera Seed in Albino Wistar Rat

Evaluations of Biochemical, Hematological and Histopathological Parameters of Subchronic Administration of Ethanol Extract of Albizia Gummifera Seed in Albino Wistar Rat

Hepatic toxicity caused by PLGA-microspheres containing usnic acid from the lichen C ladonia substellata (AHTI) during pregnancy in Wistar rats

Circulating microRNAs, potential biomarkers for drug-induced liver injury

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