Abstract:
Cancer progression, as well as the side effects of chemotherapy, have been associated with an imbalance between
ROS and the antioxidant defense system. Chemotherapeutic agents used in the treatment of cancer are known to
increase levels of ROS, free radicals and lipid peroxidation. Oxidative stress considered as a crucial mechanism
in cell injury attack and subsequent peroxidative . As a result, the appearance of often irreversible cell and tissue
toxicity and loss of the integrity of cell membranes. Thus, antioxidant compounds are seen as a promising remedy
to neutralize ROS and ensure the protection of tissues against toxicities that could suppress the development of
oxidative stress and cancers. This study aimed to evaluate the cytoprotective effect of three antioxidants, namely
CAT (catechin), Q (quercetin), and GA (gallic acid), against oxidative stress (OS) induced by etoposide. Human
red blood cells (RBCs) and hemoglobin (Hb) were pretreated with these antioxidants and then exposed to
etoposide. Several measurements were performed to assess the protective effects. The inhibition of RBCs
membrane cytotoxicity induced by etoposide by measuring cell turbidity, Hb release, methemoglobin (metHb)
generation, and intracellular Hb content. The inhibition of Hb oxidation using CAT, Q, and GA was also
evaluated by measuring Hb levels. Furthermore, this study explore the inhibition of membrane lipid peroxidation
by these antioxidants to mitigate oxidative stress induced by VP16.The results indicated that at a concentration
of 1 mM, CAT, Q, and GA enhanced cytoprotection against OS induced by VP16. Pretreatment with Q protected
human RBCs against VP16 cytotoxicity, resulting in high cellular concentration (1.068±0.021). GA also
improved the cytoprotective effect against VP16. Similarly, Hb release significantly decreased in RBCs exposed
to VP16 when pretreated with CAT, GA, and Q with Hb rates about (0.233±0.04), (0.675±0.061) and
(1.376±0.016), respectively.Moreover, the antioxidants Q, GA, and CAT exerted a highly significant inhibition
of metHb generation against VP16. The inhibition rates were 63.15%, 33.43%, and 20.68% for Q, GA, and CAT,
respectively. The intracellular Hb content was about (2.020±0.009) Q, (1.242±0.022) GA and (0.911±0.007)
CAT, it was significantly higher in RBCs pretreated with these antioxidants, indicating significant cytoprotection
against VP16. CAT, Q, and GA also protected Hb molecules against VP16-induced damage, as evidenced by
high Hb levels.Furthermore, CAT, Q, and GA exhibited inhibition of lipid peroxidation against VP16, resulting
in low levels of malondialdehyde (MDA) ranging from (0.002±0.017) to (0.054±0.002), which is a marker of
lipid peroxidation. In conclusion, the three antioxidants (CAT, Q, and GA) demonstrated the ability to inhibit
oxidative stress induced in human RBCs by VP16, a chemotherapy agent. They exerted a strong protective effect
on RBC membranes, as well as on Hb molecules, potentially mitigating the side effects of chemotherapy-induced
oxidative stress
