Rana Yehia1, Samira Saleh2, Hanan El Abhar3, Amr S Saad4, Mona Schaalan5. 1. Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Misr International University, Cairo, Egypt. Electronic address: rana.magdy@miuegypt.edu.eg. 2. Pharmacology and Toxicology Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University in Egypt (FUE), Cairo, Egypt.; Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. 3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. 4. Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt. 5. Biochemistry and Clinical Pharmacy Department, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
Abstract
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 theredox (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.
RCT Entities:
BACKGROUND: Chemotherapy-induced peripheral neuropathy is a common side effect afflicting cancerpatients treated with oxalipatin based chemotherapy. AIM: The study investigated the potential prophylactic effect of L-carnosine against acute oxaliplatinneurotoxicity in colorectal cancerpatients 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 cancerpatients by targeting Nrf-2 and NF-κB pathways.
Authors: Anna Lethicia L Oliveira; Gisele G L Santos; Renan F Espirito-Santo; Gessica Sabrina A Silva; Afrânio F Evangelista; Daniela N Silva; Milena B P Soares; Cristiane Flora Villarreal Journal: Stem Cells Int Date: 2021-01-06 Impact factor: 5.443
Authors: Jeremy Chung Bo Chiang; David Goldstein; Azadeh Tavakoli; Terry Trinh; Jacob Klisser; Craig R Lewis; Michael Friedlander; Thomas J Naduvilath; Kimberley Au; Susanna B Park; Arun V Krishnan; Maria Markoulli Journal: Sci Rep Date: 2021-11-24 Impact factor: 4.379