Antidepressants as a New Approach for Protective Interventions of Cisplatin-Induced Nephrotoxicity

El‐Arabey, Amr Ahmed; Abd-Allah, Adel R. A.

doi:10.4172/2472-1220.1000102

Cited by 3 publications

(3 citation statements)

References 26 publications

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“…In clinical practice, hydration is often used before and after chemotherapy to promote the excretion of cisplatin to prevent nephrotoxicity. Amifostine is approved by the U.S. Food and Drug Administration for use in reducing progressive nephrotoxicity of repeated cisplatin dosing in patients with advanced ovarian cancer ( el Arabey and Abd Allah, 2015 ). However, the final treatment chiefly relies on renal replacement therapy.…”

Section: Introductionmentioning

confidence: 99%

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury

Liu

Li²,

Lao³

et al. 2023

Front. Pharmacol.

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Background: Cisplatin is an effective anti-tumor drug. However, its usage is constrained by side effects such as nephron toxicity. Cisplatin-induced acute kidney injury (AKI) appears in approximately 20%–30% of cases. Hence, finding an effective protective strategy is necessary. San-Huang decoction (SHD) is a Chinese herbal decoction with good efficacy in treating chronic kidney disease (CKD). Nevertheless, the mechanism of SHD on AKI remains unclear. Consequently, we proposed to explore the potential mechanism of SHD against cisplatin-induced AKI.Methods: Active compounds, core target proteins, and associated signaling pathways of SHD were predicted through network pharmacology. Then confirmed by molecular docking. In vivo experiment, Cisplatin + SHD group was treated with SHD (6.5 g/kg/day) for 6 days before building the model. An AKI model was established with a single intraperitoneal injection of cisplatin at 20 mg/kg. After 72 h of cisplatin injection, all mice were sacrificed to collect blood and kidney tissues for verification of network pharmacology analysis.Results: We found that calycosin, rhein, and ginsenoside Rh2 may be SHD’s primary active compounds in treating cisplatin-induced AKI, and AKT, TNF-α, IL-6, IL-1β, caspase-3, and MMP9 are the core target proteins. The relationship between the compound and target protein was further confirmed by molecular docking. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses predicted that SHD has an anti-inflammatory role through the TNF and IL-17 signaling pathway. Moreover, Western blot and immunohistochemistry validated the potential molecular mechanisms of SHD, predicted from network pharmacology analysis. The mechanism of cisplatin-induced AKI involves apoptosis and inflammation. In apoptosis, Caspase-3, caspase-8, caspase-9, and Bax proteins were down-regulated, while Bcl-2 was up-regulated by SHD. The differential expression of MMP protein is involved in the pathological process of AKI. MMP9 protects from glomerular tubule damage. MMP9 and PI3K/AKT anti-apoptosis pathway were up-regulated by SHD. In addition, we discovered that SHD alleviated AKI by inhibiting the NF-κB signaling pathway.Conclusion: SHD plays a critical role in anti-inflammation and anti-apoptosis via inhibiting the NF-κB signaling pathway and activating PI3K/AKT anti-apoptosis pathway, indicating that SHD is a candidate herbal drug for further investigation in treating cisplatin-induced AKI.

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Section: Introductionmentioning

confidence: 99%

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury

Liu

Li²,

Lao³

et al. 2023

Front. Pharmacol.

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“…Yet, in spite of intense efforts over the ensuing decades to find less toxic but equally effective alternatives, CDDP continues to be widely prescribed as a standard component of treatment regimens for head and neck cancers, small-cell and nonsmall cell lung cancer, testicular cancer, ovarian, cervical cancer, bladder cancer, melanoma and others. The CDDP chief dose-limiting nephrotoxic side effect requires a reduction of the dose or discontinuation of treatment [1,2].…”

Section: Editorialmentioning

confidence: 99%

An Integrative View of Cisplatin Uptake by Kidney and Renal Toxicity

El‐Arabey¹

2018

J Kidney

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“…Amifostine is approved by the US Food and Drug Administration for Use in reducing progressive nephrotoxicity of repeated Cisplatin dosing in patients with advanced ovarian cancer. Unfortunately, even with amifostine, renal toxicity still occurs [ 44 ].…”

Section: Introductionmentioning

confidence: 99%

Nephroprotective effect of Apium graveolens L. against Cisplatin-induced nephrotoxicity

Naushad

Urooj

Ahmad

et al. 2021

Journal of Ayurveda and Integrative Medicine

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Background Cisplatin is extensively used in treating cancers, and its primary side-effect is nephrotoxicity. It accumulates in proximal convoluted tubules where it promotes cellular damage by oxidative stress, apoptosis, and inflammation, etc. In Unani medicine, Tukhm-e - Karafs (Apium graveolens L.) (TK) is mentioned in the literature to manage various kidney ailments due to its diuretic and deobstruent activities. Objective To investigate the nephroprotective effects of powder of TK in Cisplatin-induced nephrotoxicity in an animal model and to validate the Unani claim of its nephroprotective action. Material and methods In curative protocol, cisplatin (5 mg/kg body weight i.p) was administered on day one and powder of TK (500 and 1000 mg/kg p.o.) from the sixth day onwards for ten days. TK (500 and 1000 mg/kg p.o.) was given for ten days and Cisplatin (5 mg/kg body weight i.p) on day 11 in the protective model. At the end of the study, all the animals were sacrificed, and renal biochemical parameters were determined. KIM-1 level was also investigated in the kidney homogenate in conjunction with histopathological inspection of kidney tissues. Results Significant increase in serum creatinine and BUN, presence of mononuclear cell infiltration, tubular dilation and vacuolation in renal histopathology, and increased KIM-1 level confirmed the nephrotoxicity due to Cisplatin. TK's administration protects the kidney as suggested by the changes in biochemical renal function, decreased level of KIM-1, and improvement in histopathological changes. Conclusion The result advocated that TK prevented renal injury and maintained normal renal function in both models. It may be due to improved clearance of Cisplatin from kidney tubules and reduction in reactive oxygen species (ROS) produced by the inflammatory response.

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Antidepressants as a New Approach for Protective Interventions of Cisplatin-Induced Nephrotoxicity

Cited by 3 publications

References 26 publications

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury

Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury

An Integrative View of Cisplatin Uptake by Kidney and Renal Toxicity

Nephroprotective effect of Apium graveolens L. against Cisplatin-induced nephrotoxicity

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