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

Abstract

INTRODUCTION: Chemotherapy agents are widely and effectively used for the treatment of different malignant tumors. Nonetheless, their use may lead to different adverse outcomes such as nephrotoxicity which is the main cause of morbidity and hospitalization of patients in intensive care units. Melatonin is a small molecule with pleiotropic healing properties and effectiveness in the management of a wide range of diseases. 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 TO BE COVERED: To illuminate the possible role of melatonin in preventing chemotherapy-related nephrotoxicity, 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. Using predefined search terms, an exhaustive search of the titles and abstracts was carried out. Accordingly, based on a set of prespecified inclusion and exclusion criteria, twenty-one non-clinical articles were ultimately included in the study.

EXPERT OPINION: Our findings clearly demonstrate that melatonin has a protective role in 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. Meanwhile, chemosensitizing effect of melatonin that has been already reported should be examined in renal cancerous cells. The findings presented in this review are based on non-clinical studies and thus conducting appropriate clinical trials to evaluate the real effectiveness of concurrent use of chemotherapy agents with melatonin in the cancer patients is necessary.

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See also:

See also About Melatonin - In-vitro, review, and in-vivo (animals and humans) publications;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- The Di Bella Method (A Fixed Part - Cyclophosphamide and/or Hydroxyurea tablets, one or two per day);

- The Di Bella Method (A Variable Part - Selenium methonine, 40 μg capsules, twice a day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E - 30g/day orally);

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives);

- The Di Bella Method (A Fixed Part - Vitamin C/Ascorbic Acid, 2–4 grams per day, orally);

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up.