Effects of aqueous extract of
            <i>Medicago denticulata</i>
            against paracetamol‐induced hepatotoxicity in rabbits

Ahmad, Saeed; Zeb, Alam; Khan, Sanaullah

doi:10.1111/jfbc.13985

Cited by 5 publications

(2 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Increases in serum TG and TC levels induced by APAP treatment were found in several studies. 31 In our study, Feb treatment significantly reduced hepatic TG and TC levels, which might prevent the occurrence of lipid peroxidation events and oxidative stress induced by APAP overdose. A growing amount of evidence has revealed that inflammatory reactions play a critical role in further aggravating APAP-induced DILI.…”

Section: Discussionsupporting

confidence: 54%

Febuxostat ameliorates APAP-induced acute liver injury by activating Keap1/Nrf2 and inhibiting TLR4/NF-κB p65 pathways

Tian,

Zhang,

et al. 2023

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Excessive acetaminophen (APAP) application is a major cause of drug-induced liver injury (DILI). Febuxostat (Feb), a drug for reducing uric acid (UA) levels, was demonstrated to relieve hepatic inflammation and reverse organ functions. However, the effect of Feb on APAP-induced DILI and its mechanisms have not been fully explored. In this study, Feb (10 mg/kg) was given to mice by gavage 1 h after APAP (300 mg/kg, i.g.) induction. Serum and liver samples were collected 12 or 3 h after APAP challenge. Feb treatment was found to remarkably improve APAP-induced DILI, as evidenced by reduced serum ALT, AST and UA levels, pathomorphology, inflammatory, and oxidative responses. Consistently, treatment with Feb also reduced the cell injury induced by APAP in LO2 cells. Mechanistically, Feb induced GPX4 expression, activated the Keap1/Nrf2 pathway, and inhibited the TLR4/NF-κB p65 pathway. Feb also inhibited glutathione (GSH) depletion and Jun N-terminal kinase (JNK) activation in the early injury phase. Notably, pretreatment with Feb for 3 days also revealed preventive effects against APAP-induced DILI in mice. Overall, our data revealed a potential health impact of Feb on APAP-mediated DILI in vivo and in vitro, suggesting that Feb might be a potential candidate for treating DILI.

show abstract

Section: Discussionsupporting

confidence: 54%

Febuxostat ameliorates APAP-induced acute liver injury by activating Keap1/Nrf2 and inhibiting TLR4/NF-κB p65 pathways

Tian,

Zhang,

et al. 2023

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…In view of the concern caused by the hepatotoxicity of APAP, many efforts have been made to understand the mechanisms of its toxic action. Generally, APAP-induced oxidative stress and mitochondrial dysfunction play a central role in the pathogenesis of ALF (Jaeschke et al, 2012;Ahmad et al, 2021b). APAP overdose is a major cause leading to liver failure due to oxidative stress, mitochondrial and lysosomal dysfunction (Zubairi et al, 2014;Rostami et al, 2022).…”

Section: Introductionmentioning

confidence: 99%

Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

Vikulina,

Koshevoy,

Naumenko

et al. 2024

Ukr. Jour. of Vet. and Agr. Sci.

View full text Add to dashboard Cite

Changes in the redox balance at different levels, which lead to the accumulation of toxic radicals against the background of a decrease in the content of redox-active compounds, i.e., a state of oxidative stress (OS), are considered the leading pathogenetic factor in pathological conditions. Processes of peroxide oxidation of biological substrates, especially cell membrane lipids and lipophilic compounds have both regulatory and pathological effects in the body of animals and humans. For now, it remains relevant to establish the regularities of interaction of metabolism during OS development. Among the large number of existing OS models, attention is drawn to those that can be reproduced in clinical practice, as a complication of treatment measures or an error in the medical strategy, due to a constant influence on peroxidation processes in the body. Important among such means is paracetamol (acetaminophen, APAP) – one of the most common antipyretic and analgesic drugs. In addition to the known hepato-, nephro- and neurotoxic effects of its long-term and/or excessive use, there are data on reproductive toxicity and disorders of lipid metabolism. Therefore, the aim of our work was to determine the lipid profile and the level of sex hormones in male rabbits during paracetamol-induced OS. The study was performed on male rabbits of the Khila breed. According to the principle of analogs, a control group (n = 12) was formed, which were kept on a standard diet, and an experimental group (n = 12), whose animals were simulated the state of OS by oral injection of a solution of paracetamol with food at a dose of 300 mg/kg of weight body once during 21 days. The following results were obtained by determining the dynamics of changes in biochemical indicators in the rabbit body during chronic injection of paracetamol: in the rabbits of the experimental group, after the injection of paracetamol, the level of diene conjugates was 63.0 % higher, and the content of thiobarbiturate-active products was 1.26 times higher (P ˂ 0.05). A decrease in the activity of the antioxidant defence system was also noted – the amount of reduced glutathione decreased by 35.4 %, and the activity of superoxide dismutase decreased by 25.6 % (P ˂ 0.05). The obtained changes were consistent with the comprehensive indicator of total antioxidant activity, which on the 21st day of the experiment was 34.1 % lower than the values of the control group (P ˂ 0.05). At the same time, the level of steroid hormones also changed during the study – the level of total testosterone gradually decreased (on the 21st day – by 22.8 %, and at the end of the experiment – by 30.9 %, P ˂ 0.05), while the level of 17β-estradiol had an upward trend and on the 21st day was higher than the control indicators by 10.7 % (P ˂ 0.05). Significant changes in lipid metabolism were found in male rabbits – the total cholesterol content on the 21st day of the experiment exceeded the data of control animals by 25.3 %, the level of triacylglycerols – by 42.3 %, and the content of low-density lipoprotein cholesterol also increased by 1.1 times (P ˂ 0.05), and the high-density lipoprotein cholesterol level, on the contrary, was reduced by 17.0 % (P ˂ 0.05). In general, the obtained results indicate the relationship between the development of OS with changes in lipid metabolism and the balance of sex hormones, which allows us to use the model of paracetamol-induced OS in rabbits for further research.

show abstract

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

Cited by 5 publications

References 28 publications

Febuxostat ameliorates APAP-induced acute liver injury by activating Keap1/Nrf2 and inhibiting TLR4/NF-κB p65 pathways

Febuxostat ameliorates APAP-induced acute liver injury by activating Keap1/Nrf2 and inhibiting TLR4/NF-κB p65 pathways

Plasma lipid profile and sex hormone levels in rabbits under paraceta-mol-induced oxidative stress

Comprehensive review on traditional uses, phytochemistry, pharmacological properties and metal nanoparticles of a leafy vegetable, Medicago polymorpha

Contact Info

Product

Resources

About