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FIGURE 4 3.4 Nitazoxanide reduced apoptosis in rats with MTX-hepatotoxicity MTX significantly induced hepatic apoptosis as demonstrated by increased proapoptotic markers, Bax level, and caspase-3 activity (Figures 5A, D) while reduced antiapoptotic Bcl-2 level (Figure 5B) and increased Bax/Bcl-2 ratio (Figure 5C) compared to CTRL group

This leads to a situation where white blood cells such as macrophages continue producing cytokines and, while continuing their attack on foreign microbes, release reactive oxygen species (ROS) and other chemicals that harm normal tissue

2, was popularized by Lynn Margulis (then Lynn Sagan) in her 1967 publication [21], and in more detail in her subsequent books [22,23]

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