L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-κB pathways.
- 2019-02
- Toxicology and applied pharmacology 365
- Rana Yehia
- Samira Saleh
- Hanan El Abhar
- Amr S Saad
- Mona Schaalan
- PubMed: 30592963
- DOI: 10.1016/j.taap.2018.12.015
Study Design
- Type
- Randomized Controlled Trial (RCT)
- Sample size
- n = 65
- Population
- 65 colorectal cancer patients treated with oxaliplatin-based chemotherapy
- Methods
- prospective randomized controlled study design; patients randomly assigned to Arm A (FOLFOX-6 regimen) or Arm B (FOLFOX-6 regimen and daily oral L-carnosine 500 mg)
- Blinding
- Open-label
- Duration
- three months
- Funding
- Unclear
Background
Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancer patients treated with oxalipatin based chemotherapy.Aim
The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatin neurotoxicity in colorectal cancer patients with emphasis on the redox (Nrf-2, MDA), inflammatory (NF-κB, TNF-α), and apoptotic (caspase-3) parameters.Methods
In this pilot study, 65 patients were recruited using a prospective randomized controlled study design and enrolled randomly into two arms; Arm A, 31 patients received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B, 34 patients received FOLFOX-6 regimen and daily oral L-carnosine (500 mg) along the treatment period. Patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTC version 4).Results
The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal. In arm B, the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%) and TNF-α (36.6%); this anti-inflammatory effect entailed also its anti-oxidative and anti-apoptotic effects, thus MDA level (51.8%) and caspase-3 activity (49%) were also reduced, whereas Nrf-2 was increased (38.7%) as compared to Arm A. In both arms a significant correlation was only evident between TNF-α and the neuropathy grading score (P < .03); the correlation analysis was significantly positive between NF-κB and both Nrf-2 and caspase 3.Conclusion
L-Carnosine exerted a neuroprotective effect against oxaliplatin-induced peripheral neuropathy in colorectal cancer patients by targeting Nrf-2 and NF-κB pathways.Research Insights
Nrf-2 was increased (38.7%) as compared to Arm A
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 500 mg/day
caspase-3 activity (49%) were also reduced
- Effect
- Beneficial
- Effect size
- Large
- Dose
- 500 mg/day
MDA level (51.8%) ... was also reduced
- Effect
- Beneficial
- Effect size
- Large
- Dose
- 500 mg/day
the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%)
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 500 mg/day
the addition of L-carnosine decreased significantly the levels/activity of NF-κB (27%)
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 500 mg/day
The neuropathy grading evaluation of Arm B vs Arm A revealed that 17 patients (56.7%) vs 11 patients (35.5%) suffered grade 1, one patient (3.3%) vs 19 patients (61.3%) suffered grade 2, while 12 patients (40%) vs one patient (3.2%) were normal.
- Effect
- Beneficial
- Effect size
- Large
- Dose
- 500 mg/day
TNF-α (36.6%)
- Effect
- Beneficial
- Effect size
- Moderate
- Dose
- 500 mg/day