ArticlePharmacognosy magazine2016
Protective Mechanisms of Thymoquinone on Methotrexate-induced Intestinal Toxicity in Rats.
Article in Pharmacognosy magazine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Recent Perspectives on the Physiological and Therapeutic Benefits of Placental Extracts in Chronic Noninfectious Diseases and Aging.Current medicinal chemistry · 2026Pooled it
- Article
- Hesperidin loaded bilosomes mitigate the nephrotoxicity induced by methotrexate; biochemical and molecular in vivo investigations.BMC nephrology · 2025Article
- Accidental methotrexate overdose leading to multisystem toxicity: A case report.Toxicology reports · 2024Article
- Molecular mechanisms underlying methotrexate-induced intestinal injury and protective strategies.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Comparative Study of the Protective Effects of Citral, Thymoquinone, and Silymarin on Methotrexate-induced Cardiotoxicity in Rats.Journal of pharmacopuncture · 2024Article
- Mechanistic aspects of ameliorative effects of Eicosapentanoic acid ethyl ester on methotrexate-evoked testiculopathy in rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Effect of thymoquinone on NRF2/NF-kB/MAPK pathway in methotrexate-induced rat testis injury.Iranian journal of basic medical sciences · 2024Article
- Effect ofCurrent issues in molecular biology · 2023Review
- Beneficial role of naringin against methotrexate-induced injury to rat testes: biochemical and ultrastructural analyses.Redox report : communications in free radical research · 2022Article
- Insights into the Protective Effects of Thymoquinone against Toxicities Induced by Chemotherapeutic Agents.Molecules (Basel, Switzerland) · 2021Review
- Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses.Cancer chemotherapy and pharmacology · 2021Article
- Update on Pharmacological Activities, Security, and Pharmacokinetics of Rhein.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- Pharmacomicrobiology of Methotrexate in Rheumatoid Arthritis: Gut Microbiome as Predictor of Therapeutic Response.Frontiers in immunology · 2021Review
- Thymoquinone-chemotherapeutic combinations: new regimen to combat cancer and cancer stem cells.Naunyn-Schmiedeberg's archives of pharmacology · 2020Review
- Ameliorative effect of nicorandil in ovarian ischemia-reperfusion-induced injury in rats: role of potassium channel.Naunyn-Schmiedeberg's archives of pharmacology · 2020Article
- The Possible Contribution of P-Glycoprotein in the Protective Effect of Paeonol against Methotrexate-Induced Testicular Injury in Rats.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Protective effects of thymoquinone and diallyl sulphide against malathion-induced toxicity in rats.Environmental science and pollution research international · 2020Article
- Paeonol Attenuates Methotrexate-Induced Cardiac Toxicity in Rats by Inhibiting Oxidative Stress and Suppressing TLR4-Induced NF-Mediators of inflammation · 2020Article
- Ameliorative effects of silymarin on HCl-induced acute lung injury in rats; role of the Nrf-2/HO-1 pathway.Iranian journal of basic medical sciences · 2019Article
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Authors and funding
3 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntestinal toxicity is a serious side effect in methotrexate (MTX) chemotherapy.
objectiveTo investigate the mechanisms by which the anticancer drug MTX-induced intestinal damage could be prevented by thymoquinone (TQ), an active ingredient of Nigella sativa. MATERIALS AND
methodsTQ was given orally for 10 days, and MTX toxicity was induced at the end of day 3 of the experiment, with or without TQ pretreatment.
resultsMTX caused intestinal damage, represented by distortion in normal intestinal histological structure, with significant oxidative stress, exhibited as decrease in reduced glutathione concentration and catalase activity, along with significant increase in malondialdehyde level compared to control group. MTX also caused nitrosative stress evident by increased intestinal nitric oxide (NO) level, with up-regulation of inducible NO synthase expression shown in immunohistochemical staining. Furthermore, MTX caused inflammatory effects as evident by up-regulation of intestinal necrosis factor-kappa beta and cyclooxygenase-2 expressions, which were confirmed by increased intestinal tumor necrosis factor-alpha level via enzyme-linked immunosorbent assay. Moreover, MTX caused apoptotic effect, as it up-regulated intestinal caspase 3 expression. Concomitant TQ significantly reversed the MTX-induced intestinal toxic effects by reversing intestinal microscopic damage, as well as significantly improving oxidative/nitrosative stress, inflammatory and apoptotic markers tested compared to MTX alone.
conclusionTQ may possess beneficial intestinal protective effects as an adjuvant co-drug against MTX intestinal toxicity during cancer chemotherapy. TQ protection is conferred via antioxidant, anti-nitrosative, anti-inflammatory, and anti-apoptotic mechanisms. SUMMARY: Methotrexate induces oxidative and nitrosative stress in intestinal tissuesMethotrexate also initiates inflammatory and apoptotic intestinal injuryThymoquinone co-administration ameliorates methotrexate-induced intestinal toxicityThymoquinone has antioxidative, anti-nitrosative, anti-inflammatory, and anti-apoptotic mechanisms. Abbreviations used: COX-2: Cyclooxygenase-2, ELISA: Enzyme-linked immunosorbent assay, H and E: Hematoxylin and eosin, iNOS: Inducible nitric oxide synthase, MDA: Malondialdehyde, MTX: Methotrexate, NO: Nitric oxide, NF-κB: Nuclear factor-κB, GSH: Reduced glutathione, TQ: Thymoquinone, TNF-α: Tumor necrosis factor-alpha.
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