Assessment of Paclitaxel toxicity in the model organism Caenorhabditis elegans.

CANDELARIA GONZALES MORENO; PATRICIA LUCERO; VICTORIA LEONHARD; ROXANA ALASINO; MIRIAM VIRGOLINI

Congreso; Third Latin American C. elegans Meeting; 2023

Paclitaxel is a plant alkaloid extracted from the bark of the Pacific yew tree. This agent works by disrupting the microtubular network essential for cell division and other normal cell functions, ultimately causing cell death. These properties determine its therapeutic uses as an antitumor drug and the need for toxicity assessment. In this study, the round-worm Caenorhabditis elegans was selected as an experimental model to evaluate paclitaxel in a solution. Two exposure times: 1 h and 24 h, and 3 concentrations: 100 ng/ml, 500 ng/ml, and 1000 ng/ml, in addition to the control group and vehicle (DMSO), were assessed in liquid medium in triplicate in a total of four independent samples. Lethality, size (length and area), and locomotion were evaluated in adult (larval stage L4) N2 (wild type) worms. The results evidenced a 100% survival for all doses and exposure times. Interestingly, a dose-dependent effect was seen in the worm’s size and locomotor parameters provided by the Microtracker device (Phylumtech S.A.) such as average speed and distance travelled. The results demonstrate the sensitivity of the invertebrate C. elegans to detect subtle effects in the nanosafety evaluation of therapeutic agents. These tests represent the basic parameters to be used for the nanosafety evaluation of different Paclitaxel nanoformulations currently being studied. Financing agencies: PICT 2017-0874 and PICT 2019-02444 from ANPCyT (MBV).