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

Abstract

Aims Investigate Melatonin administration along with Vincristine (VCR) owing to two reasons: First, Melatonin’s sciatic nerve protective effect against Chemotherapy Induced Peripheral Neuropathy (CIPN). Second, Vincristine’s anticancer work potentiation that may lead to a decrease in its dose and its side effects accordingly.

Main methods 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 (neuroleptic) were co-administered with the aim of investigating the degeneration/protection of the sciatic nerve. Tail Immersion Test and histopathological analyses were done to validate the experimental model (induction of rat peripheral neurodegeneration) and examine the possible Melatonin and Pregabalin protective/analgesic effects respectively. Liver and kidney function tests, catalase activity and malondialdehyde (MDA) level were measured. Concerning the in vitro experiment, cell viability assays in addition to ELISA (for caspases 3&9) were conducted using HCT-116 colon cancer cell line treated with VCR, Melatonin and their combination.

Key findings VCR caused an elevated level of oxidation (MDA level increment) in the sciatic nerve, while Melatonin could prove 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 in addition to the synergistic effect of combining Melatonin to VCR on the cellular apoptotic level (caspases 3&9 increased activity levels) and inhibitory concentration 50%.

Significance Melatonin possesses an antioxidant property that can protect the sciatic nerve from CIPN-induced degeneration and potentiate VCR's anticancer effect at the same time