The effects of acetyl-l-carnitine on house ear institute-organ corti 1 (hei-oc1) and htb-186 medulloblastom a cells against cisplatin and radiotherapy ototoxicity

Radiotherapy and Chemotherapeutic agents such as cisplatin (CDDP) may produce toxic effects either alone or in combination in cancer treatments. The aim of this study was to investigate in in-vitro models the protective effects of Acetyl-L-Carnitine (ALC) against radiotherapy (RT) and CDDP on the cochlea and medulloblastoma cells. The possible side effects were deciphered in biochemical and molecular levels. Chemotherapy, radiotherapy and chemoradiotherapy were used on HEI-OC1 cohlea and HTB-186 medulloblastoma cells to investigate cell viability, apoptosis, MDA, caspase3-8-9, mitochondrial membrane potential, ROS, GSSG/GSH as well as Nrf2 and related genes expressions were investigated. In the SPSS22 program for statistical analysis parametric t-test was performed and p<0.05 was considered statistically significant. IC50 doses were in HEI-OC1 (72h) and HTB-186 (24h) cells; 5 Gy RT, 50 μM CDDP (HEI-OC1), 75 μM CDDP (HTB-186), 50 ALC (HEI-OC1) and 25 μM ALC (HTB-186). In HEI-OC1 cells in comparison to control group; by using ALC+CDDP, apoptosis, MDA, ROS, Nrf2 activation and expressions of Nrf2, GR, NQO1, GST genes and in ALC+RT apoptosis, MDA, ROS, HO-1 and in Nrf2 activations NQO1, SOD3 genes expression as well as in ALC+CDDP+RT apoptosis, MDA, ROS, HO-1 activation and expression of Nrf2, GR, HO-1, NQO1, SOD2, SOD3, GPx, GST, Gclm and catalase genes were increased. HTB-186 cells in comparison to control group; ALC+CDDP+RT apoptosis, MDA, ROS, HO-1 and Nrf2 activations and GR, Gclm, NQO1, catalase genes expressions also in CDDP+RT apoptosis, MDA, caspase 3-8-9, ROS, HO-1 activation increased and the expression levels of GR, NQO1, Glcm and catalase genes levels were down-regulated. In our study especially in chemotherapy+ALC group it was observed that the expression levels of Nrf2, antioxidant and phase II detoxifying genes were induced in the ear cells. When chemoradiotherapy+ALC was applied to medulloblastoma cells, induced oxidative stress related genes like as Nrf2 however at the same time antioxidant and phase II detoxifying genes expressions levels were decreased. Key Words: Cohlea, Medulloblastoma, Acetyl-L-Carnitine, Cisplatin, Radiation