Study of the possible synergistic protective effects of Melatonin and Pregabalin in Vincristine induced peripheral neuropathy Wistar Albino rats

Abstract

Chemotherapy Induced Peripheral Neuropathy (CIPN) results from some widely used chemotherapeutic agents as Vincristine (VCR). CIPN can turn so tough that a reduction in the chemotherapy dose is a must.

Melatonin (an antioxidant) can be used to counteract VCR's CIPN effect on the sciatic nerve and potentiate its anticancer effect in colon cancer.

In vivo and in vitro experiments were conducted in the study. The in vivo experiment included developing a CIPN Wistar Albino rat model. They were injected with VCR sulfate to induce CIPN, while Melatonin and Pregabalin were co-administered with the aim of investigating the degeneration/protection of the sciatic nerve and toxicity level. Tail Immersion Test (TIT) and histopathological analyses were done to validate the experimental model (induction of rat peripheral neurodegeneration) and examine the possible Melatonin synergistic effect.

Concerning the in vitro experiment, cell viability tests in addition to apoptotic assays were conducted using HCT-116 colon cancer cell line treated with VCR, Melatonin and their combination. Liver and kidney function tests, catalase activity and malondialdehyde (MDA) levels were measured.

VCR caused an elevated level of oxidation (MDA level increase) in the sciatic nerve, while Melatonin could proof its antioxidant effect through increasing catalase activity (antioxidant enzyme) with no significant toxic effect on body's functions. HCT-116 in-vitro test proved the strong cytotoxic effect of VCR and Melatonin synergism on the apoptosis level (Caspases 3 and 9 increased levels) and inhibitory concentration 50%.

In conclusion, Melatonin possesses an antioxidant effect that can protect the sciatic nerve from degeneration and potentiate VCR's anticancer effect at the same time.

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See also:

- Official Web Site: The Di Bella Method;

- 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;

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

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- 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 - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

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

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

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