The influence of small doses of paracetamol on rabbit liver

Maciejewska-Paszek, Izabela; Pawłowska-Góral, Katarzyna; Kostrzewski, M.; Kurzeja, Ewa; Wardas, Maria; Rzepecka‐Stojko, Anna

doi:10.1016/j.etp.2007.04.003

Cited by 8 publications

(3 citation statements)

References 10 publications

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“…One group served as negative control (control) and was provided with normal feed while the other group was positive control fed with 200 mg/kg paracetamol (PC). Previous studies showed that hepatotoxicity in rabbits was induced at low doses to 1 g/kg rabbits (Maciejewska‐Paszek et al., 2007; Zubairi et al., 2014). The 200 mg/kg of MD was fed to another group and represented as extract control (EC).…”

Section: Methodsmentioning

confidence: 99%

Effects of aqueous extract of Medicago denticulata against paracetamol‐induced hepatotoxicity in rabbits

2021

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Medicago denticulata is commonly used as a leafy vegetable, salad, and food ingredient. In this study, different doses of leaves aqueous extract of M. denticulata (MD) were fed to intoxicated rabbits with paracetamol (100, 200, and 300 mg/kg) for regular 21 days. The aqueous extract was evaluated for phenolic composition using HPLC‐DAD. Serum biochemical and hematological parameters were studied to check its activity. The liver was examined histologically and for antioxidant status. Results revealed that paracetamol led to a significant alteration in all the hematological (RBC, WBC, Hb, PLT, and HCT), and serum lipid parameters (TC, HDL, LDL, and TG) while MD at the dose rate of 300 mg/kg had a curative effect on the stabilization of the affected parameters. The high dose of MD ameliorated different antioxidant parameters such as reduced glutathione (GSH), DPPH radical scavenging activity (RSA), and thiobarbituric acid reactive substances (TBARS) of the liver on day 21st of the treatment. Histological studies revealed significant paracetamol‐induced toxicity of the liver, whereas the MD had positive effects on induced toxicity. Improvement in all these alterations confirms the curative potential of Medicago denticulata extract. Practical applications Paracetamol is a well‐known antipyretic and analgesic medicine. However, it has been found to cause toxicity including hepatotoxicity. Synthetic drugs such as statins, antibiotics, and anti‐viral are used for curing hepatic diseases also cause severe side effects. Thus, nutraceuticals from plant foods are used to reduce the side effects of different hepatotoxic medicine are continuously researched. This study reported for the first time that aqueous extract of the plant leaves was protective against the hepatotoxicity induced by paracetamol.

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Section: Methodsmentioning

confidence: 99%

Effects of aqueous extract of Medicago denticulata against paracetamol‐induced hepatotoxicity in rabbits

2021

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“…In the future, a dose-escalating study of paracetamol and sunitinib should be conducted due to the lack of data concerning different doses of paracetamol coadministered with sunitinib. Taking into consideration the common use of acetaminophen, coadministration of low doses of paracetamol used for extended period of time (Kim et al 2009b ; Maciejewska-Paszek et al 2007 ; Haznedar et al 2009 ) should be examined.…”

Section: Discussionmentioning

confidence: 99%

The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide

Karbownik

Szałek

Sobańska

et al. 2014

Eur J Drug Metab Pharmacokinet

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The study aimed to examine the effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite, paracetamol glucuronide. Both drugs share metabolic pathways in the liver, and the drug interactions between sunitinib and paracetamol administered in higher doses were reported. These interactions resulted in hepatotoxicity. The adult New Zealand male rabbits were divided into three groups (6 animals each): rabbits receiving sunitinib and paracetamol (SUN + PC), rabbits receiving sunitinib (SUN), and a control group receiving paracetamol (PC). Sunitinib was administered orally (25 mg) and paracetamol was administrated intravenously (35 mg/kg). Blood samples for sunitinib and SU12662 assays were collected up to 96 h after drug administration and for paracetamol and paracetamol glucuronide up to 300 min after drug administration. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin were analysed before and after drug administration. A number of pharmacokinetic parameters were analysed. There were no differences in the levels of AST, ALT, and bilirubin among the groups at either time point. Significantly higher values of AUC0–t, AUC0–∞, and Cmax and lower clearance and volume of distribution of paracetamol were observed in group PC vs. group SUN + PC (p < 0.01). The maximum plasma concentration of paracetamol glucuronide tended to be higher in group PC 213.27 μg/mL (90 % CI 1.06, 1.25; p = 0.0267). Statistically significant differences were revealed for paracetamol glucuronide mean residence time (MRT); MRT was higher in group SUN + PC than in group PC (p = 0.0375). The mean tmax of paracetamol glucuronide was similar in both groups: SUN + PC and group PC (15 and 20 min, respectively). The mean tmax of sunitinib was different in groups SUN + PC and SUN (10.0 and 7.0, respectively; p = 0.0134). At the studied doses, neither of the drugs, whether administered alone or together, had hepatotoxic effects. The present study was not able to confirm that sunitinib, administered at low doses in conjunction with paracetamol, displays a hepatoprotective effect. Significant differences were observed in some pharmacokinetic parameters of paracetamol.

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“…Paracetamol has been shown to exert toxic effects to common laboratory animal models, such as rodents (Moldéus 1978;Rikans and Moore 1988;Maciejewska-Paszeka et al 2007), but also to human patients (Larson 2007;Mitchell et al 2011), and these findings raised concerns regarding its environmental relevance (see de Voogt et al 2009). Paracetamol is a model hepatotoxicant, especially at greater doses, which was already fully documented in both experimental animals and humans (Brind 2007;Hinson et al 2004;Jaeschke and Bajt 2006;Jaeschke et al 2003;Prescott 1980;Xu et al 2008).…”

Section: Introductionmentioning

confidence: 98%

Preliminary evaluation of Diopatra neapolitana regenerative capacity as a biomarker for paracetamol exposure

Freitas

Coelho

Pires

et al. 2015

Environ Sci Pollut Res

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An increasing number of studies established unequivocal relationships between exposure to pharmaceutical drugs and toxicity in wildlife. However, few studies investigated physiological alterations caused by such compounds in polychaetes. Thus, in this study, the effects of increasing concentrations of paracetamol were studied in the polychaete Diopatra neapolitana using tissue regenerative capacity as a biomarker. The obtained results revealed that individuals exposed to ecologically relevant concentrations (namely, 25 μg/L) of paracetamol exhibited significantly lower capacity to regenerate their body in comparison with control organisms. This study evidenced that paracetamol can induce significant physiological alterations in D. neapolitana resulting in an overall diminished regenerative capacity, which is of significance to a species with high ecological and economic relevance. Additionally, this study indicates the promise of D. neapolitana as a test organism in laboratory-based bioassays, but also as an adequate sentinel species to pharmaceutical drugs.

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The influence of small doses of paracetamol on rabbit liver

Cited by 8 publications

References 10 publications

Effects of aqueous extract of Medicago denticulata against paracetamol‐induced hepatotoxicity in rabbits

Effects of aqueous extract of Medicago denticulata against paracetamol‐induced hepatotoxicity in rabbits

The effect of sunitinib on the plasma exposure of intravenous paracetamol and its major metabolite: paracetamol glucuronide

Preliminary evaluation of Diopatra neapolitana regenerative capacity as a biomarker for paracetamol exposure

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