Dexamethasone and Citicoline Mitigate Cisplatin-Induced Peripheral Neuropathy: A Novel Experimental Study in Mice.

Abstract

Objectives: Given the rising prevalence of cisplatin-induced peripheral neuropathy (CisIPN), investigations to alleviate its adverse effects are required. Oxidative stress and free radical development are essential pathways of CisIPN. Specifically, dexamethasone and citicoline are characterized by anti-inflammatory and antioxidant activities that might reduce CisIPN incidence and severity. The current study assessed the possible impacts of novel interventions, dexamethasone, and, citicoline on CisIPN.

Materials and methods: Seventy-two male mice were randomly allocated into nine groups (n: 8/each group). Different doses of dexamethasone (7.5, 15, 30 mg/kg, i.p.), citicoline (10, 20, 40 mg/kg, i.p.), and the combination (dexamethasone 7.5 mg/kg + citicoline 10 mg/kg, i.p.) were injected in the first three days and one day before receiving cisplatin (2 mg/kg, i.p.). The tail-flick method was used for assessing nociception. Besides, malondialdehyde (MDA), interleukin-1 beta (IL-1β), tumor necrosis factor-α (TNF-α), total antioxidant capacity (TAC), and mice weight differences (ΔW) were measured.

Results: Different doses of dexamethasone and citicoline enhanced latency time (p<0.05). Moreover, dexamethasone 15 mg/kg diminished the level of MDA and increased TAC (p<0.05) and in 30 mg/kg, MDA was reduced (p<0.05). Besides, 20 and 40 mg/kg of citicoline reduced MDA and elevated TAC (p<0.05), and 10 mg/kg merely reduced MDA (p<0.05). Dexamethasone in all doses declined IL-1β and TNF-α levels, and citicoline only at 40 mg/kg lessened their levels (p<0.05). Interestingly, ΔW declined more in the dexamethasone and citicoline groups than the cisplatin group (p<0.05).

Conclusion: Dexamethasone and citicoline attenuate CisIPN through anti-inflammatory activity, improving the antioxidant capacity, and inhibiting lipid peroxidation.