Abstract
Oxaliplatin treatment is associated with the development of a dose-limiting painful neuropathy impairing patient’s quality of life. Since oxidative unbalance is a relevant mechanism of oxaliplatin neurotoxicity, we assessed the potential antioxidant properties of Vitis vinifera extract in reducing oxaliplatin-induced neuropathy as a valuable therapeutic opportunity. A hydroalcoholic extract of Vitis vinifera red leaf was characterized and tested in primary rat astrocyte cells treated with oxaliplatin (100 μM). Oxaliplatin lethality in the human adenocarcinoma cell line HT-29 was evaluated in the absence and presence of the extract. In vivo, pain hypersensitivity was measured in a rat model of neuropathy induced by oxaliplatin and ex vivo molecular targets of redox balance were studied. Vitis vinifera extract (50 μg mL−1, 4 h incubation) significantly reduced the oxaliplatin-dependent superoxide anion increase and lipid peroxidation in rat astrocytes but did not interfere with the mortality elicited by oxaliplatin in HT-29 cancer cells. In oxaliplatin-treated rats, a repeated daily administration of the Vitis vinifera extract (300 mg kg−1, p.o.) significantly prevented mechanical and thermal hypersensitivity to noxious and non noxious stimuli. mRNA and protein levels of Nrf2 were normalized in spinal cord and DRGs. Moreover, in the spinal cord, the extract significantly decreased the activation of astrocytes. Vitis vinifera reduced oxidative damages and relieved pain without influencing oxaliplatin anti-cancer activity.
Highlights
Oxaliplatin, a third-generation platinum-based anticancer agent, is mainly used in the treatment of colorectal cancer[1]
According to the liquid chromatography- mass spectrometry (LC-MS) method developed by means of a UHPLC-qToF the Vitis Vinifera leaf freeze dried extract metabolomic profile reported in the Fig. 1 has been collected
Aimed to evaluate a possible interaction between the treatment with Vitis vinifera extract and the therapeutic properties of oxaliplatin, we investigated the vitality of the human colorectal cancer cell line HT-29
Summary
Oxaliplatin, a third-generation platinum-based anticancer agent, is mainly used in the treatment of colorectal cancer[1]. It generates the cross-link DNA that leads to the replication failure of cancer cells and has improved cancer therapy[2,3]. Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of oxaliplatin. Various studies have reported that natural products could be a great source of new therapeutic compounds essential in treatment of disorder related to pain[6,7,8]. Chemical composition of Vitis vinifera leaves is known very well, the studies conducted on the biological effects of the leaves are limited
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