Melatonin protects against methotrexate-induced memory deficit and hippocampal neurogenesis impairment in a rat model

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Published on Monday, 04 March 2019

Abstract

Methotrexate (MTX) is a chemotherapy agent linked to cognitive deficits in cancer patients received chemotherapy treatment. MTX decreases cell proliferation in the hippocampus, which is concomitant with cognitive deficits in animal models.

The present study aimed to investigate the disadvantages of MTX on cognition associated with cell division, survival, and immature neurons involved in hippocampal neurogenesis, as well as the practical neuroprotective effects of melatonin.

Male Sprague Dawley rats were given two injections of MTX (75 mg/kg) on days 8 and 15 followed by Leucovorin (LCV, 6 mg/kg) at hours 18, 26, 42, 50 via i.p. injection. Some rats received co-treatment with melatonin (8 mg/kg, i.p. injection) for 15 days before and during MTX administration (preventive), 15 days after MTX administration (recovery), or both (30 days total; throughout).

Hippocampal-dependent memory was examined using novel objection location (NOL) and novel object recognition (NOR) tests. Cell division, survival and immature neurons in the subgranular zone (SGZ) in the hippocampus were evaluated using immunofluorescence staining.

Rats given MTX/LCV were found to have cognitive memory deterioration based on the NOL and NOR tests.

Moreover, reductions in cell division, cell survival, and the numbers of immature neurons were detected in the MTX/LCV group when compared to the controls.

This damage was not observed in rats in the preventive, recovery, or throughout groups.

These findings reveal that melatonin has the potential to diminish the negative effects of MTX on memory and neurogenesis.

This also indicates the benefit of melatonin co-administration in patients who undergo chemotherapy treatment.

 

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See also:

- Official Web Site: The Di Bella Method;

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

- 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;

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

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- 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;

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- 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;

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- 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.