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Molecular evidence of the inhibitory potential of melatonin against sodium arsenite toxicity

Published on Tuesday, 18 February 2025

Abstract

Introduction: Sodium arsenite (SA), NaAsO2, is among the most hazardous toxicants, and wide use and presence of this toxicant leads to a severe environmental threat. Exposure to SA is associated with many health concerns, such as the prevalence of cancer and diabetes mellitus type 2 (DMT2). Many studies suggest that SA induces inflammation and biochemical impairments through different mechanisms, including increasing oxidative stress and altering vital genes such as biochemical and anti-inflammatory. Recent studies on melatonin (MLT), a harmless hormone secreted in the body generally for induction of sleepiness, find many beneficial and positive effects. Mitigating different harms and toxicities through different mechanisms, such as antioxidant properties, anti-inflammatory effects, and critical gene regulation, is essential. Due to these findings, this study aimed to evaluate the hypothesis that MLT may ameliorate pancreatic damage caused by exposure to SA.

Methods: Forty-eight adult healthy male wistar rats aged 7-8 weeks were divided into eight for this research. Group 1 did not receive any intervention. Group 2 received 10 mg/kg/day MLT through intraperitoneal (IP) injection. Groups 3, 4, and 5 received 1.5 (1/10 LD50), 5 (1/3 LD50), and 7.5 (1/2 LD50) mg/kg SA, respectively. Groups 6, 7, and 8 were given 1.5 (1/10 LD50), 5 (1/3 LD50), and 7.5 (1/2 LD50) mg/kg of SA along with 10 mg/kg/day MLT, respectively, during the last ten days of the experiment. After 28 days of the experiment, the blood and tissue samples of the pancreas were removed for biochemical and pathological examination.

Results: MLT attenuates SA toxicity by reducing oxidative stress biomarkers and inflammation markers. Moreover, MLT improves SA exposure's biochemical and functional damages by regulating related genes and pathways.

Conclusion: MLT poses protective and preventive effects on the pancreas against exposure to SA. However, MLT's therapeutic and beneficial impacts have great potential for further investigation.

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About this publication.

- 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 - Calcium, 2 grams per day, orally);

The Di Bella's Method: Use of Melatonin since 1974 - together with others chemical compounds - in several Oncological Pathologies:

- 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;