Protective Effects of Crocin Against Methotrexate-Induced Hepatotoxicity in Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

Kader, Ghada Abdel; Abdelaziz, Eman Z.; Hassan, Ranya; Greish, Sahar M; Abogresha, Noha M.; Sultan, Basma O; Yousef, Einas; Morsi, Shereen

doi:10.7759/cureus.34468

Cited by 2 publications

References 32 publications

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Spirulina and Thymoquinone Protect Against Methotrexate-Induced Hepatic Injury in Rats

Behairy,

Elkomy,

Elsayed

et al. 2023

Rev. Bras. Farmacogn.

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Methotrexate is a chemotherapy medication frequently used to treat various forms of cancer. The purpose of this research was to examine if the administration of Arthrospira platensis (Spirulina) and/or thymoquinone could ameliorate the liver injury resulting from methotrexate. The rats were randomly assigned to seven groups, each containing seven rats. The groups included a control group that received only saline, a group that received A. platensis orally at a dose of 500 mg/kg, a group that received thymoquinone orally at a dose of 10 mg/kg, a group that received a single i.p. dose of 20 mg/kg methotrexate, a group that received both A. platensis and methotrexate, a group that received both thymoquinone and methotrexate, and a group that received A. platensis, thymoquinone, and methotrexate. The injection of methotrexate caused an increase in the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, triacylglycerides, and low-density lipoprotein-cholesterol, and a decrease in high-density lipoprotein-cholesterol (HDL-cholesterol). The liver tissues also showed an increase in malondialdehyde and a decrease in reduced glutathione, superoxide dismutase, and catalase, along with pathological lesions and increased expression of TNF-α and caspase-3. However, administration of A. platensis and thymoquinone alone or in combination reduced the toxicity and apoptosis induced by methotrexate. Graphical Abstract

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Spirulina and Thymoquinone Protect Against Methotrexate-Induced Hepatic Injury in Rats

Behairy,

Elkomy,

Elsayed

et al. 2023

Rev. Bras. Farmacogn.

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Garden cress oil attenuates methotrexate-induced hepatic damage by enhancing inflammation, apoptosis, and histological profile: in vivo and in silico studies

Mabrouk,

El-Akad,

Afifi

et al. 2024

Preprint

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Methotrexate (MTX) has been used in high doses for cancer therapy and low doses for autoimmune diseases. It is proven that methotrexate-induced hepatotoxicity occurs even at relatively low doses. It is known that garden cress has anti-inflammatory, antioxidant, and hepatoprotective properties. This study investigates the potential alleviating effect of garden cress oil (GCO) against MTX-induced hepatotoxicity in rats. The chemical composition of GCO was assessed using GC/MS analysis. Liver damage was studied using molecular and histological analysis. Also, the effects of GCO on TNF-α and caspase-3 proteins were evaluated through molecular docking studies. MTX showed clear signs of apoptosis, such as increased mRNA expression levels of BAX, Caspase-3, and P53, and increased liver inflammation indicated by higher levels of TNF-α expression. MTX exhibited significant liver damage, as demonstrated by histological examination. Treatment with GCO effectively alleviated the apoptotic effects of MTX and provided protection against inflammation, as well as restoring histological alterations. Molecular docking revealed that linoleic acid and α-tocopherol are recognized as leading compounds for attenuating the inflammatory and apoptosis cascade reactions in the liver by inhibiting TNF-α and caspase-3 proteins, and in vivo and in silico studies demonstrated that GCO could potentially alleviate MTX hepatotoxicity.

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Protective Effects of Crocin Against Methotrexate-Induced Hepatotoxicity in Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study

Cited by 2 publications

References 32 publications

Spirulina and Thymoquinone Protect Against Methotrexate-Induced Hepatic Injury in Rats

Spirulina and Thymoquinone Protect Against Methotrexate-Induced Hepatic Injury in Rats

Garden cress oil attenuates methotrexate-induced hepatic damage by enhancing inflammation, apoptosis, and histological profile: in vivo and in silico studies

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