Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose

Waring, W. Stephen; Stephen, A F L; Robinson, O D G; Dow, Margaret; Pettie, Janice

doi:10.1093/qjmed/hcn023

Cited by 24 publications

(21 citation statements)

References 21 publications

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“…The ammonia molecules combine to form urea, which is then deposited in the blood and transported to the kidneys for excretion. Higher than normal levels of serum BUN indicate malfunctioning of kidneys, whereas lower levels of serum BUN indicate liver disease or damage or malnutrition (Gregory, 2003;Waring et al, 2008). In our findings, serum BUN level in the paracetamol group was lower than that of the control group (13.85 ± 1.20 vs. 20.52 ± 0.67 mg/dL).…”

Section: Analysis Of Oxidative Biomarkersmentioning

confidence: 40%

“…In our findings, serum BUN level in the paracetamol group was lower than that of the control group (13.85 ± 1.20 vs. 20.52 ± 0.67 mg/dL). Similarly, Waring et al (2008) reported that BUN is decreased in the serum of mice administered paracetamol, which may be due to paracetamol-induced hepatotoxicity. However, in the current study, when WPH was administered orally and intraperitoneally (preventive and curative groups), BUN increased to normal in the curative group (20.01 ± 1.22 mg/dL), was slightly lower in the preventive (17.09 ± 1.03 mg/dL) and oral (17.97 ± 1.55 mg/dL) groups compared with the control group, but was significantly higher than in the paracetamol (control, no WPH) group of mice (Table 1).…”

Section: Analysis Of Oxidative Biomarkersmentioning

confidence: 88%

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Ameliorative potential of whey protein hydrolysate against paracetamol-induced oxidative stress

Athira

Mann

Sharma

et al. 2013

Journal of Dairy Science

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The aim of the present study was to validate the antioxidant effect of whey protein hydrolysate (WPH) using a small animal model. Paracetamol is common drug that is safe at therapeutic levels; however, an overdose causes oxidative stress, which may lead to potential hepatic and renal necrosis. The protective effect of WPH against paracetamol-induced hepato-nephrotoxicity in mice was investigated in this study. The WPH was prepared by hydrolyzing ultrafiltered retentate of mozzarella cheese whey with commercial food-grade alcalase; the resulting WPH had substantial in vitro antioxidant activity. Male albino mice were treated with WPH for 4 d [intraperitoneally at 4 mg/kg of body weight (BW) per day or orally at 8 mg/kg of BW per day] before or after oral administration of paracetamol (300 mg/kg of BW) for 2 d. Two control groups were used; the negative control mice were administered water only; the paracetamol group was administered paracetamol at 300 mg/kg of BW but received no WPH. Levels of different marker enzymes (glutamate pyruvate transaminase and alkaline phosphatase), creatinine, and blood urea nitrogen were measured in the experimental animal blood sera. The WPH successfully mitigated the increase in the concentration of oxidative biomarkers such as glutathione pyruvate transaminase, alkaline phosphatase, and creatinine, and restored the level of blood urea nitrogen to normal in sera of mice in which oxidative stress was induced with an overdose of paracetamol. Furthermore, the indices of different antioxidant enzymes, such as catalase, superoxide dismutase, and glutathione peroxidase, and lipid peroxidation end-products were determined in liver homogenate. The mice that were given WPH, either intraperitoneally or orally, showed increased activities of antioxidant enzymes and a reduction in thiobarbituric acid reactive substances (TBARS) compared with the paracetamol control group. The protective effect of WPH was less when administered orally than intraperitoneally. We concluded that WPH is the potential protector against paracetamol-induced hepato-nephrotoxicity and can be effectively used in health-promoting foods as a biofunctional ingredient.

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Section: Analysis Of Oxidative Biomarkersmentioning

confidence: 40%

Section: Analysis Of Oxidative Biomarkersmentioning

confidence: 88%

Ameliorative potential of whey protein hydrolysate against paracetamol-induced oxidative stress

Athira

Mann

Sharma

et al. 2013

Journal of Dairy Science

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“…The present resulted indicated that lipid peroxidation might be a contributing factor to the development of renal toxicity, Ghosh et al (2010) found that exposure of rats with a nephrotoxic dose of APAP elevated a number of biomarkers as BUN and creatinine levels, and the authors explained these disturbances to renal oxidative stress, decreased antioxidant activity, elevated renal tumor necrosis factor-a (TNF-a) and nitric oxide (NO) levels demonstrating deterioration of renal function. Contradictory with the finding of Kuhad et al (2007), Waring et al (2008) reported that low serum urea concentrations were encountered in a high proportion of patients after APAP overdose. This is likely to be explained by a high prevalence of risk factors for hepatotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic and protective effects of Caesalpinia gilliesii and Cajanus cajan proteins against acetaminophen overdose-induced renal damage

et al. 2013

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The present work aims to evaluate the protective and ameliorative effects of two plant-derived proteins obtained from the seeds of Cajanus cajan and Caesalpinia gilliesii(Leguminosae) against the toxic effects of acetaminophen in kidney after chronic dose through determination of certain biochemical markers including total urea, creatinine, and kidney marker enzyme, that is, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In addition histopathological examination of intoxicated and treated kidney with both proteins was performed. The present results show a significant increase in serum total urea and creatinine, while significant decrease in GAPDH. Improvement in all biochemical parameters studied was demonstrated, which was documented by the amelioration signs in rats kidney architecture. Thus, both plant protein extracts can counteract the nephrotoxic process, minimize damage to the kidney, delay disease progression, and reduce its complications.

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“…However, there are difficulties in relying on patient reporting, and errors may occur concerning the reported drug name, dose and timing of ingestion (Zyoud et al 2012; Hewett et al 2013; Rutter et al 2013). A history of acute or chronic alcohol ingestion and biochemical tests of malnutrition have been explored as means of detecting an increased susceptibility to paracetamol liver toxicity; however, none of these are sufficiently reliable for routine clinical application (Waring et al 2008a, b, d; Zyoud et al 2011). …”

Section: Introductionmentioning

confidence: 99%

The 100 most influential publications in paracetamol poisoning treatment: a bibliometric analysis of human studies

et al. 2016

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BackgroundAnalysis of the most influential publications within paracetamol poisoning treatment can be helpful in recognizing main and novel treatment issues within the field of toxicology. The current study was performed to recognize and describe the most highly cited articles related to paracetamol poisoning treatment.MethodsThe 100 most highly cited articles in paracetamol poisoning treatment were identified from the Scopus database in November 2015. All eligible articles were read for basic information, including total number of citations, average citations per year, authors’ names, journal name, impact factors, document types and countries of authors of publications.ResultsThe median number of citations was 75 (interquartile range 56–137). These publications were published between 1974 and 2013. The average number of years since publication was 17.6 years, and 45 of the publications were from the 2000s. A significant, modest positive correlation was found between years since publication and the number of citations among the top 100 cited articles (r = 0.316; p = 0.001). A total of 55 journals published these 100 most cited articles. Nine documents were published in Clinical Toxicology, whereas eight documents were published in Annals of Emergency Medicine. Citations per year since publication for the top 100 most-cited articles ranged from 1.5 to 42.6 and had a mean of 8.5 citations per year and a median of 5.9 with an interquartile range of 3.75–10.35. In relation to the origin of the research publications, they were from 8 countries. The USA had the largest number of articles, 47, followed by the UK and Australia with 38 and nine articles respectively.ConclusionsThis study is the first bibliometric assessment of the top 100 cited articles in toxicology literature. Interest in paracetamol poisoning as a serious clinical problem continues to grow. Research published in high-impact journals and from high income countries is most likely to be cited in published paracetamol research.

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Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose

Abstract: Low serum urea concentration is not an independent risk factor for hepatotoxicity after paracetamol overdose.

Cited by 24 publications

References 21 publications

Ameliorative potential of whey protein hydrolysate against paracetamol-induced oxidative stress

Ameliorative potential of whey protein hydrolysate against paracetamol-induced oxidative stress

Therapeutic and protective effects of Caesalpinia gilliesii and Cajanus cajan proteins against acetaminophen overdose-induced renal damage

The 100 most influential publications in paracetamol poisoning treatment: a bibliometric analysis of human studies

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