Vitamin C (Ascorbic acid) protects from neuropathy caused by cisplatin, through enhanced heat shock protein-70 and reduced oxidant effect

Abstract

OBJECTIVE:We aimed to determine whether vitamin C has a protective effect on cisplatin-induced neuropathy in rats. METHODS: In total, 24 rats were included in the study of which 8 rats (no drug administered) were categorized as the control group. The remaining 16 rats were given a total dose of 20 mg/kg cisplatin to induce neuropathy. These drug-administered rats (16 rats) were randomly divided into two groups, namely, group-1 (n=8): cisplatin+saline and group-2 (n=8): cisplatin+vitamin C (500 mg/kg/day). All rats were tested for motor function and electromyographic activity 3 days after cisplatin. Motor performance was evaluated by an inclined-plane test. Compound muscle action potential was evaluated. Plasma malondialdehyde, glutathione, tumor necrosis factor-α, interleukin 6, and sciatic nerve HSP 70 levels were measured. Axon diameter and nerve growth factor expression levels were analyzed. RESULTS: Plasma malondialdehyde, tumor necrosis factor-α, and interleukin 6 levels were higher in the cisplatin+saline group than control group (p<0.001). But vitamin C significantly reduced malondialdehyde and inflammatory cytokine levels when compared with the cisplatin+saline group (p<0.001). Glutathione levels were lower in both cisplatin+saline and cisplatin+vitamin C groups than control group, but vitamin C significantly ameliorated the glutathione levels (p<0.05). Sciatic heat shock protein-70 levels were significantly higher in the cisplatin+vitamin C group than cisplatin+saline group. Compound muscle action potential amplitude and inclined plane test scores were significantly improved in the vitamin C group (p<0.05). Axon diameter and nerve growth factor expression ameliorated with vitamin C (p<0.05). CONCLUSIONS: We demonstrated the ameliorated effects of vitamin C on cisplatin-induced neuropathy through increased heat shock protein-70, nerve growth factor levels, and reduced inflammatory and oxidant effects. The results are promising to improve the neurotoxic effects of cisplatin in cancer patients.

A case for the use of chemotherapy in hereditary mitochondrial optic neuropathies: Successful administration of cisplatin/etoposide in a male patient with testicular seminoma and Leber's hereditary optic neuropathy

“…The relative safety of chemotherapy in LHON may be bolstered through the use of adjunct antioxidant treatments. Our patient was treated with high‐dose vitamin C based on evidence of faster visual recovery for LHON patients noted in one study for those treated with idebenone, vitamins B2 and C. 12 Some studies have shown improved biochemical marker profiles, compound muscle action potential amplitudes and motor performance in rats with cisplatin‐induced neuropathy treated with vitamin C. 20 However, the role of chemoprotective agents more generally in mitigating the neurotoxicity of platin‐based chemotherapy agents remains controversial, with insufficient evidence to support routine use. There have been traditional concerns that treatment efficacy may be compromised by antioxidant activity, although this has not been supported in the literature as found by one systematic review.…”

Vitamins in neuropathy: pathophysiological and therapeutic roles

“…There is a need for clinical trials on vitamin C supplementation in individuals with a DFU to fill the knowledge gap and guide clinical practice [34]. Vitamin C could ameliorate CIPN probably through increased heat shock protein-70, increased level of nerve growth factor, and reduced inflammatory and oxidant effects [35]. Vitamin C may act as an independent preventive factor for complex regional pain syndrome (CRPS).…”