ArticleSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society2020
Amlodipine alleviates cisplatin-induced nephrotoxicity in rats through gamma-glutamyl transpeptidase (GGT) enzyme inhibition, associated with regulation of Nrf2/HO-1, MAPK/NF-κB, and Bax/Bcl-2 signaling.
Article in Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 27 citations in OpenAlex.
- Renoprotective effects of perampanel against cisplatin-induced acute kidney injury: managing NLRP3-pyroptosis and enhancement of antioxidant defense.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Metabolic dynamics and stage-specific biomarkers in chronic HBV infection: a metabolomics study.BMC gastroenterology · 2025Article
- Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Review
- Glutathione‑degrading enzymes in the complex landscape of tumors (Review).International journal of oncology · 2024Review
- Berberine Alleviates Doxorubicin-Induced Myocardial Injury and Fibrosis by Eliminating Oxidative Stress and Mitochondrial Damage via Promoting Nrf-2 Pathway Activation.International journal of molecular sciences · 2023Article
- Amelioration of ethanol-induced gastric ulcer in rats by quercetin: implication of Nrf2/HO1 and HMGB1/TLR4/NF-κB pathways.Heliyon · 2022Article
- Nephrotoxicity in cancer treatment: An update.Advances in cancer research · 2022Article
- Salvianolic Acid C Protects against Cisplatin-Induced Acute Kidney Injury through Attenuation of Inflammation, Oxidative Stress and Apoptotic Effects and Activation of the CaMKK-AMPK-Sirt1-Associated Signaling Pathway in Mouse Models.Antioxidants (Basel, Switzerland) · 2021Article
- Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery.Antioxidants (Basel, Switzerland) · 2021Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
backgroundThe therapeutic utility of the effective chemotherapeutic agent cisplatin is hampered by its nephrotoxic effect. We aimed from the current study to examine the possible protective effects of amlodipine through gamma-glutamyl transpeptidase (GGT) enzyme inhibition against cisplatin nephrotoxicity.
methodsAmlodipine (5 mg/kg,
resultsAmlodipine alleviated renal injury that was manifested by significantly diminished serum creatinine and blood urea nitrogen levels, compared to cisplatin group. Amlodipine inhibited GGT enzyme, which participates in the metabolism of extracellular glutathione (GSH) and platinum-GSH-conjugates to a reactive toxic thiol. Besides, amlodipine diminished mRNA expression of NADPH oxidase in the kidney, while enhanced the anti-oxidant defense by activating Nrf2/HO-1 signaling. Additionally, it showed marked anti-inflammatory response by reducing expressions of p38 mitogen-activated protein kinase (p38 MAPK) and nuclear factor-kappa B (NF-κB), with subsequent down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1). Moreover, amlodipine reduced Bax/Bcl-2 ratio and elevated hepatocyte growth factor (HGF), thus favoring renal cell survival.
conclusionsEffective GGT inhibition by amlodipine associated with enhancement of anti-oxidant defense and suppression of inflammatory signaling and apoptosis support our suggestion that amlodipine could replace toxic GGT inhibitors in protection against cisplatin nephrotoxicity.
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