Effects of curcumin and B1-6-12 on alterations in cell viability, oxidative stress, expression of tight junction proteins and barrier property of endothelial cell and pericyte induced by cisplatin and oxaliplatin in vitro

Abstract

Cisplatin and oxaliplatin are platinum chemotherapeutic drugs that can cause peripheral neuropathy. Nowadays, the pathogenesis of cisplatin/oxaliplatin-induced neuropathy has not been completely elucidated. Emerging evidence revealed that both drugs cause vascular complications. Both drugs might damage nerve capillaries leading to cisplatin/oxaliplatin-induced neuropathy. The objective of this study is to examine the effect of curcumin and B1-6-12 on cisplatin and oxaliplatin-induced alterations in cell viability, apoptosis (caspase-3), oxidative stress (ROS and GSH/GSSG ratio), expression of tight junction proteins (claudin-5, occludin, ZO-1, and ZO-2), and barrier property in endothelial cell and pericyte in vitro. Human umbilical vein endothelial cell (HUVEC) and human brain vascular pericyte (HBVP) were utilized as a model of endothelial cells and pericytes, respectively. Cisplatin caused the reduction of cell viability, induction of caspase-3, overproduction of oxidative stress, depletion of tight junction protein expression, and barrier dysfunction in both HUVEC and HBVP. Co-treatment with curcumin improved these toxic effects in both cells. Moreover, co-treatment with B1-6-12 improved all damage except oxidative stress in both HUVEC and HBVP. Oxaliplatin also caused alterations in HUVEC and HBVP similar to cisplatin and curcumin relieved the alterations in both cell types. In contrast, B1-6-12 was not effective against oxaliplatin-induced cytotoxicity in both HUVEC and HBVP. The combination of curcumin and B1-6-12 was not significantly more effective than curcumin or B1-6-12 alone in most parameters. Both curcumin and B1-6-12 are effective against cisplatin-induced endothelial cell and pericyte cytotoxicity: however, only curcumin is the potential treatment against oxaliplatin-induced microvascular damage. In addition, it is not worth combining these two agents for the management of platinum chemotherapy-induced microvascular toxicity.