Melatonin protected against kidney impairment induced by 5-fluorouracil in mice

Published on Sunday, 13 August 2023

Abstract

The utility of 5-fluorouracil (5-FU) as a successful chemotherapeutic drug for several cancers is limited by the induction of kidney injury and dysfunction due to redox imbalance, inflammation, and apoptosis.

Meanwhile, melatonin (MLT) is a potent antioxidant and anti-inflammatory natural compound with a wide safety range. The current study aimed to investigate MLT's protective effect against 5-FU-induced kidney impairment.

Male mice were given multiple doses of 5-FU at 25 and 100 mg/kg, as well as MLT at 20 mg/kg. MLT treatment alleviated the toxic effect of 5-FU by normalizing blood urea and creatinine levels and preserving the histological structure, indicating MLT's nephroprotective ability.

This is accompanied by body weight maintenance, an increase in survival percentage, and preserved hematological parameters in comparison to the 5-FU-treated mice.

MLT's renoprotective effect was explained by improvements in C-reactive protein, IL-6, and caspase-3 in kidney tissue, indicating MLT's anti-inflammatory and antiapoptotic ability.

Furthermore, MLT inhibited 5-FU-induced lipid peroxidation by maintaining the activity of superoxide dismutase and catalase, as well as glutathione levels in kidney tissue from mice treated with both doses of 5-FU.

The current findings show that MLT has a novel protective effect against 5-FU-induced renal injury and renal impairment.

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- 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 use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- 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;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- 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;