1. Background
Chemotherapy-induces peripheral neuropathy (CIPN) is a common
complication of chemotherapy agents with a significant impact on
patients’ quality of life. The risk of developing CIPN is higher among
conventional chemotherapy drugs especially with platinum (e.g.,
cisplatin and oxaliplatin), taxanes, and vinca alkaloids [1, 2].
The development of CIPN during antineoplastic therapy is one of the most
common cause of the termination or modification of cancer treatment
[3]. Peripheral neuropathy may present as sensory, motor, or
autonomic dysfunction. Clinical signs of neurological complications
include paresthesia, numbness of the fingers, gait disturbance, ataxia,
loss of deep tendon reflexes, wrist or foot drop, facial nerve palsy,
and optic neuropathy [4, 5].
The functional impairment of neurons induced by chemotherapeutic drugs
may be mediated through oxidative stress, inflammation, apoptosis and
electrophysiological disturbances [6]. In oxidative stress, the
release of oxygen free radicals including hydrogen peroxide, superoxide
ions, and nitric oxide causes changes in cell components which may lead
to lipid peroxidation and subsequent cell death [7-9]. Silymarin is
a flavonoid mixture extracted from Silybum marianum seed, which consists
of a mixture of flavolignans including silibinin, isosilibinin,
silicristin, and silidianin [10]. Although silymarin has been mostly
known as its hepatoprotective properties [11], growing evidence has
shown the neuroprotective effects of silymarin in neurodegenerative
diseases, such as Alzheimer’s disease, Parkinson’s disease, and cerebral
ischemia, via reducing reactive oxygen species (ROS), decreasing
inflammatory cytokines, and altering cellular apoptosis pathway
[12]. Beside the positive effect on CIPN, Laboratory data show that
silymarin and its compounds (especially silibinin) have strong
anticarcinogenic effect against cancer cells such as breast cancer and
human promyelocytic leukemia HL-60 cells [13, 14].
It is acknowledged that the treatment of peripheral neuropathy is
difficult and completely relieve of peripheral neuropathy (especially
associated pain) may not occur with current therapies and complementary
therapies may help in better management of CIPN [4, 15, 16].
The aim of this study was to evaluate the efficacy and side effects of
silymarin in the treatment of peripheral neuropathy caused by
chemotherapy drugs.