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Updated: May 25, 2026
Nerve Excitability Assessment in Chemotherapy-induced Neurotoxicity
Published on: April 26, 2012
Oxaliplatin-induced neuropathy: oxidative stress as pathological mechanism. Protective effect of silibinin
Lorenzo Di Cesare Mannelli1, Matteo Zanardelli, Paola Failli
1Deparment of Preclinical and Clinical Pharmacology, University of Florence, Florence, Italy. lorenzo.mannelli@unifi.it
Unlabelled:
Oxaliplatin is the standard treatment for advanced colorectal cancer. Its dose-limiting toxicity is the development of a painful neuropathic syndrome sustained by unclear mechanisms. Although the oxidative hypothesis is a matter of debate, direct data about oxidative damage induced in vivo by anticancer agents are lacking and the efficacy of the available antioxidant compounds are unsatisfactory. In a rat model of painful oxaliplatin-induced neuropathy (2.4 mgkg(-1) i.p., daily for 21 days), we described an important component of oxidative stress. In the plasma of oxaliplatin-treated rats, the increases in carbonylated protein and thiobarbituric acid reactive substances were the index of the resultant protein oxidation and lipoperoxidation, respectively. The same pattern of oxidation was revealed also in the sciatic nerve, and in the spinal cord where the damage reached the DNA level. The antioxidant compound silibinin (100 mgkg(-1) per os), administered once a day, starting from the first day of oxaliplatin injection until the 20th, prevented oxidative damage as did α-tocopherol. Repetitive administration of silibinin, as well as α-tocopherol, reduced oxaliplatin-dependent pain induced by mechanical and thermal stimuli. Antioxidants were also able to improve motor coordination. The antineuropathic effect of both molecules improved by about 50% oxaliplatin-induced behavioral alterations.
Perspective:
This study characterizes oxidative stress parameters in a rat model of oxaliplatin-induced neuropathy. A relationship between the improvement of oxidative alterations and pain relief is established in rats treated with natural antioxidant compounds like α-tocopherol and silibinin. Silibinin could be a valid therapeutic option for chemotherapy-induced neuropathy.
Insights
Oxaliplatin chemotherapy causes painful neuropathy by inducing oxidative stress. Natural antioxidants like silibinin and α-tocopherol effectively reduced pain and improved motor function in a rat model.
Area of Science:
- Neuroscience
- Pharmacology
- Biochemistry
Background:
- Oxaliplatin is a key treatment for advanced colorectal cancer, but its use is limited by dose-limiting neuropathic pain.
- The mechanisms underlying oxaliplatin-induced neuropathy are not fully understood, with oxidative stress being a debated factor.
- Existing antioxidant treatments for chemotherapy-induced neuropathy have shown limited efficacy.
Purpose of the Study:
- To investigate the role of oxidative stress in oxaliplatin-induced neuropathy using a rat model.
- To evaluate the efficacy of the natural antioxidant silibinin and α-tocopherol in preventing and treating oxaliplatin-induced neuropathy.
Main Methods:
- A rat model was established by daily intraperitoneal injection of oxaliplatin for 21 days.
- Oxidative stress markers, including protein carbonylation and lipoperoxidation, were measured in plasma, sciatic nerve, and spinal cord.
- The effects of silibinin and α-tocopherol on pain behavior, motor coordination, and oxidative damage were assessed.
Main Results:
- Oxaliplatin treatment significantly increased markers of oxidative damage in plasma, sciatic nerve, and spinal cord, including DNA damage.
- Daily administration of silibinin (100 mg/kg) or α-tocopherol prevented these oxidative alterations.
- Both antioxidants significantly reduced oxaliplatin-induced pain and improved motor coordination, with a ~50% improvement in behavioral alterations.
Conclusions:
- Oxaliplatin-induced neuropathy in rats is characterized by significant oxidative stress at molecular and cellular levels.
- Natural antioxidants silibinin and α-tocopherol demonstrate significant antineuropathic effects, correlating with the reduction of oxidative damage.
- Silibinin presents a promising therapeutic potential for managing chemotherapy-induced neuropathy.
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