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Review
. 2024 Dec;37(6):1325-1378.
doi: 10.1007/s10534-024-00637-7. Epub 2024 Sep 30.

Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence

Ademola C Famurewa  1   2   3 , Mina Y George  4 , Cletus A Ukwubile  5 , Sachindra Kumar  6 , Mehta V Kamal  7 , Vijetha S Belle  7 , Eman M Othman  8   9   10 , Sreedhara Ranganath K Pai  6
Affiliations
Review

Trace elements and metal nanoparticles: mechanistic approaches to mitigating chemotherapy-induced toxicity-a review of literature evidence

Ademola C Famurewa et al. Biometals. 2024 Dec.

Abstract

Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.

Keywords: Apoptosis; Cancer; Cancer therapy; Chemotherapy; Metal nanoparticles; Trace elements.

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Conflict of interest statement

Declarations. Conflict of interests: The authors declare no competing interests.

References

    1. Abd El-Aal SA, AbdElrahman M, Reda AM, Afify H, Ragab GM, El-Gazar AA, Ibrahim SSA (2022) Galangin mitigates DOX-induced cognitive impairment in rats: Implication of NOX-1/Nrf-2/HMGB1/TLR4 and TNF-α/MAPKs/RIPK/MLKL/BDNF. Neurotoxicology 92(July):77–90. https://doi.org/10.1016/j.neuro.2022.07.005 - DOI - PubMed
    1. Abd El-Twab SM, Hozayen WG, Hussein OE, Mahmoud AM (2016) 18β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Ren Fail 38(9):1516–1527. https://doi.org/10.1080/0886022X.2016.1216722 - DOI - PubMed
    1. Abd-Allah S, Hashem KS (2015) Selenium nanoparticles increase the testicular antioxidant activity and spermatogenesis in male rats as compared to ordinary selenium. Int J Adv Res 3:792–802
    1. Abdelghffar EA, Obaid WA, Mohammedsaleh ZM, Ouchari W, Eldahshan OA, Sobeh M (2022) Ajwa dates (Phoenix dactylifera L.) attenuate cisplatin-induced nephrotoxicity in rats via augmenting Nrf2, modulating NADPH oxidase-4 and mitigating inflammatory/ apoptotic mediators. Biomed Pharm 156:113836 - DOI
    1. Abd-Elmawla MA, Abdelalim E, Ahmed KA, Rizk SM (2023) The neuroprotective effect of pterostilbene on oxaliplatin-induced peripheral neuropathy via its anti-inflammatory, anti-oxidative and anti-apoptotic effects: comparative study with celecoxib. Life Sci 315:121364. https://doi.org/10.1016/j.lfs.2022.121364 - DOI - PubMed

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