The protective role of melatonin in chemotherapy‐induced nephrotoxicity: a systematic review of non-clinical studies

ABSTRACT

Introduction: The aim of this study was to investigate the potential role of melatonin in the prevention of chemotherapy-induced nephrotoxicity at the preclinical level.

Areas covered: To illuminate the possible role of melatonin in preventing chemotherapy-related nephrotoxicity, Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. A comprehensive search strategy was developed to include PubMed, Web of Science, Scopus, and Embase electronic databases from their inception to May 2018. Based on a set of prespecified inclusion and exclusion criteria, 21 non-clinical articles were ultimately included in the study.

Expert opinion: Our findings clearly demonstrate that melatonin has a protective role in the prevention of chemotherapy-induced nephrotoxicity which may be caused by different chemotherapy agents such as cyclophosphamide, cisplatin, doxorubicin, methotrexate, oxaliplatin, etoposide, and daunorubicin. On the basis of current review of non-clinical studies, this protective effect of melatonin is attributed to different mechanisms such as reduction of oxidative stress, apoptosis, and inflammation. The findings presented in this review are based on non-clinical studies and thus conducting appropriate clinical trials to evaluate the real effectiveness of the concurrent use of chemotherapy agents with melatonin in the cancer patients is necessary.

KEYWORDS:

• Cancer
• chemotherapy
• kidney
• melatonin
• nephrotoxicity
• systemic review
• toxicity

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Article Highlights

• The current study is a systematic review of the non-clinical publications about the protective effects of melatonin on chemotherapy-induced nephrotoxicity.

• The kidney is particularly vulnerable to the cytotoxic effects of chemotherapy, which is caused through different mechanisms such as oxidative stress, inflammation, and apoptosis.

• Due to its different antioxidative, anti-inflammatory, and anti-apoptotic properties, melatonin can serve as a protective role in chemotherapy-induced nephrotoxicity.

• This review showed that when melatonin is used in combination with chemotherapeutic agents surprisingly does not reduce their anticancer effects, but reduces nephrotoxicity that brings us to the conclusion that melatonin works with mechanisms other than oxidative stress somehow making a differentiation between normal and cancer cells.

• The conclusion of this article is limited to non-clinical studies, but regarding the chemosensitizing effects of melatonin on cancer cells, more detailed studies should be carried out in both preclinical and clinical levels to confirm the exact benefit of concurrent therapy of chemotherapy agents and melatonin in cancer and the reduction of nephrotoxicity.

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Acknowledgments

This invited paper is the outcome of an in-house, financially non-supported study. Authors wish to thank TUMS and INSF in providing full-text of the articles needed. Authors wish to thank Fatima Isamil Hassan for assisting in English language editing.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

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Funding

This paper was not funded.