Abstract
Pharmaceuticals are actually identified as a threat to the ecosystem. Nowadays, the growing consumption of antineoplastic agents has been related to their continuous input in natural environments. These substances can interfere with physiological and biochemical processes of aquatic species over their entire life cycle. Oxaliplatin (OXA) is a widely used chemotherapeutic agent to treat colon or rectal cancer. This study was aimed to evaluate the developmental toxicity of the OXA exposure. To this end, zebrafish embryos were incubated with 0.001, 0.1, 0.5 mg/L OXA. At different timepoints mortality rate, hatching rate, developmental abnormalities, histological analysis, oxidative stress and mRNA expression of gene related to oxidative stress were evaluated. Our results showed that OXA exposure can induce increased mortality and developmental abnormalities reducing the hatching rate. Histological analysis demonstrated that OXA induced liver, intestine, muscle and heart injury. Superoxide dismutase and catalase activities were significantly increased after OXA exposure demonstrating its oxidative effects. The mRNA expression levels of apoptosis-related genes (caspase-3, bax and bcl-2) were significantly upregulated by OXA exposure. In conclusion, we highlighted that OXA exposure led to a dose-related developmental toxicity, oxidative stress and apoptosis.
Highlights
Global Cancer Statistics 2020 (GLOBOCAN) estimates that 19.3 million new cancer cases and about 10.0 million cancer deaths occurred globally in 2020
OXA selectively inhibits the synthesis of deoxyribonucleic acid (DNA), the guanine and cytosine content correlates with the degree of OXA-induced cross-linking
The results indicate that OXA in a dose dependent manner induced cell death in zebrafish embryos
Summary
Global Cancer Statistics 2020 (GLOBOCAN) estimates that 19.3 million new cancer cases and about 10.0 million cancer deaths occurred globally in 2020. Platinum-based antineoplastic agents are widely used in chemotherapy. They crosslink DNA strands or form DNA-protein crosslinks in cancer cells [1,2] and include cisplatin (CDDP), carboplatin (CARP) and oxaliplatin (OXA). OXA is a chemotherapeutic agent used to treat colon or rectal cancer that has spread (metastasized) [5]. It is frequently used in conjunction with other anticancer medications (fluorouracil and leucovorin). The anticancer mode of action of platinum-complex drugs is owing to the development of platinum adjuncts between adjacent DNA bases, and it is classed as “alkylating agent”.
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