Amino acid modified [70] fullerene derivatives with high radical scavenging activity as promising bodyguards for chemotherapy protection

Yue Zhou,Jiasheng Zheng,Chunying Shu,Chunru Wang,Mingming Zhen,Wei Li,Tong Yu,Mirong Guan,Liang Ma

doi:10.1038/s41598-018-34967-7

Abstract

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients’ organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and β-alanine were separately employed to chemically modify C70 fullerene, and L-lysine derivative of fullerene (C70-Lys) exhibits superior radical scavenging activity to β-alanine derivative of C70 (C70-Ala). As expected, C70-Lys show much better protective effect than C70-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.

Highlights

Chemotherapy is currently the mainstream for clinical cancer treatments, but the severe side effects of chemotherapeutic drugs are extremely hard to reduce[1,2,3]
Certain free radicals know as reactive oxygen species (ROS) are considered to be an important factor for oxidative stress and damage, which leads to the imbalance of oxidant-antioxidant systems[12,13]
The ratio of nitrogen to carbon (N/C) from the elemental analysis was used to assess the average number of amino acid group, approximately with eight L-lysine and six β-alanine molecules severally attached to the fullerenes

Summary

Introduction

Chemotherapy is currently the mainstream for clinical cancer treatments, but the severe side effects of chemotherapeutic drugs are extremely hard to reduce[1,2,3]. It is of great significance to seek a chemical species with a high efficiency to scavenge free radicals, both for preserving our health and for utilization of cancer chemotherapy. Water solubility and biocompatibility, such as the carboxyl-modified[18], hydroxylated (known as fullerenols)[19], ethylenediamine-modified[20] and amino acid modified fullerenes and metallofullerenes[21], all of which exhibit different degrees of antioxidant activities in vitro or in vivo. Some other hydrophilic fullerene derivatives have been studied for their protection against chemotherapy medicines induced free radical damage[23,24]. We investigated the chemical and physical properties of the derivatives and discovered that the L-lysine derivative of fullerene (C70-Lys) exhibited better capability in scavenging ROS than the β-alanine derivative fullerene (C70-Ala). For the hepatoprotective and cardioprotective effects against DOX, as well as the cytoprotective effect on human umbilical vein endothelial cells (HUVECs), the C70-Lys were more excellent than that of the C70-Ala, which attributed to the different modifications on the fullerene surface

Methods

Results

Conclusion