Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPARγ and Nrf2: Protective effect of 18β-Glycyrrhetinic acid.

  title={Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPAR$\gamma$ and Nrf2: Protective effect of 18$\beta$-Glycyrrhetinic acid.},
  author={Ayman Moawad Mahmoud and Omnia E. Hussein and Walaa G. Hozayen and Sanaa M. Abd El-Twab},
  journal={Chemico-biological interactions},

Chicoric acid prevents methotrexate hepatotoxicity via attenuation of oxidative stress and inflammation and up-regulation of PPARγ and Nrf2/HO-1 signaling

CA prevented oxidative stress, inflammation, and liver injury induced by MTX by activating Nrf2 /HO-1 signaling and PPARγ and inhibited apoptosis in MTX-administered rats.

Ferulic acid prevents oxidative stress, inflammation, and liver injury via upregulation of Nrf2/HO-1 signaling in methotrexate-induced rats

Ferulic acid prevented MTX hepatotoxicity by activating Nrf2/HO-1 signaling and PPARγ, and attenuating oxidative stress, inflammation, and cell death, and prevented all histological alterations, ameliorated liver function markers, and boosted antioxidants in MTX-induced rats.

Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis.

Drug-induced nephrotoxicity contributes to acute kidney injury (AKI) and represents a major problem in the clinical setting. We investigated the possible involvement of NLRP3 inflammasome activation

Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses

HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.

Galangin mitigates oxidative stress, inflammation, and apoptosis in a rat model of methotrexate hepatotoxicity

Gal possesses a hepatoprotective effect mediated by attenuating oxidative damage, inflammation, and apoptosis in rats, which relieved liver injury, ameliorated liver function, oxidative stress, and inflammation markers, and increased antioxidants in MTX-treated rats.

Ellagic acid reduces methotrexate-induced apoptosis and mitochondrial dysfunction via up-regulating Nrf2 expression and inhibiting the IĸBα/NFĸB in rats

The clinical application of methotrexate (MTX), an efficacious cytotoxic drug, is restricted due to its associated liver toxicity. Ellagic acid (EA), a natural polyphenol, possesses hepatoprotective,

Activation of pCREB/Nrf-2 signaling mediates re-positioning of liraglutide as hepato-protective for methotrexate -induced liver injury (MILI).

Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death

PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice, suggesting that PU may have great therapeutic potential for the prevention of methotrexate-induced hepatotoxicity.



18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants

Findings make 18β-GA candidate as a potent agent in preventing MTX-induced kidney injury with possible mechanisms of attenuating oxidative stress and inflammation through up-regulating the Nrf2/ARE signaling.

Hesperidin protects against cyclophosphamide-induced hepatotoxicity by upregulation of PPARγ and abrogation of oxidative stress and inflammation.

  • A. Mahmoud
  • Biology, Medicine
    Canadian journal of physiology and pharmacology
  • 2014
The study suggests that hesperidin exerts its protective effect against CYP-induced hepatotoxicity through upregulation of hepatic PPARγ expression and abrogation of inflammation and oxidative stress.

The Protective Effect of Glycyrrhetinic Acid on Carbon Tetrachloride-Induced Chronic Liver Fibrosis in Mice via Upregulation of Nrf2

Results suggested that GA can protect the liver from oxidative stress in mice, presumably through activating the nuclear translocation of Nrf2, enhancing the expression of its target genes and increasing the activity of the antioxidant enzymes.

Gamma-Glutamylcysteine Ethyl Ester Protects against Cyclophosphamide-Induced Liver Injury and Hematologic Alterations via Upregulation of PPARγ and Attenuation of Oxidative Stress, Inflammation, and Apoptosis

Pretreatment with GCEE protected against CP-induced hepatotoxicity, possibly by activating PPARγ, preventing GSH depletion, and attenuating oxidative stress, inflammation, and apoptosis.

Berberine mitigates cyclophosphamide-induced hepatotoxicity by modulating antioxidant status and inflammatory cytokines

Berberine showed a marked hepatoprotective effect against CP-induced hepatotoxicity through alleviation of the elevated serum marker enzymes in addition to its antioxidant and anti-inflammatory efficacies.

Mechanisms of Thymoquinone Hepatorenal Protection in Methotrexate-Induced Toxicity in Rats

Using TQ concurrently with MTX restored kidney and liver functions, as well as their normal histology, and TQ may be beneficial adjuvant that confers hepatorenal protection to MTX toxicity via antioxidant, antinitrosative, anti-inflammatory, and antiapoptotic mechanisms.

Protective Effects of Glycyrrhizic Acid and 18β-Glycyrrhetinic Acid against Cisplatin-Induced Nephrotoxicity in BALB/c Mice.

Oral administration of GA or 18βGA significantly reduced CP-induced increases in the levels of blood urea nitrogen, creatinine, and lactate dehydrogenase, and it was demonstrated that GA and 18 βGA rendered renal cells resistant toCP-induced HMGB1 cytoplasmic translocation and release.

Peroxisome Proliferator Activator Receptor (PPAR)-γ Ligand, but Not PPAR-α, Ameliorates Cyclophosphamide-Induced Oxidative Stress and Inflammation in Rat Liver

Activation of PPAR-γ, but not PPar-α, conferred protection against CP-induced hepatotoxicity, via activation of antioxidant and anti-inflammatory mechanisms, and may serve as supplement during CP chemotherapy.

Neuroprotective effects of glycyrrhizic acid and 18beta-glycyrrhetinic acid in PC12 cells via modulation of the PI3K/Akt pathway.

The results suggest that GA may protect PC12 cells from ischemic injury via modulation of the intracellular antioxidant system and mitochondria-induced apoptosis and suggest that the cytotoxicity of 6-OHDA may influence the mitochondrial Bax/Bcl-2 ratio without altering the expression of Bax.