Protective role of <i>Silybum marianum</i> against hepatorenal toxicity induced by copper oxide nanoparticles in male albino rats: genetic and histological studies

Copper oxide nanoparticles (CuONPs) are widely used in gas sensors, high- temperature conductors, and as antimicrobial agents, yet concerns remain regarding their potential toxicity. <i>Silybum marianum</i> (SM), or milk thistle, is known for its hepatoprotective and antioxidant properties. This study aimed to assess the genetic and pathogenic effects of CuONPs on adult male Wistar albino rats and to evaluate the protective role of milk thistle. Thirty-two male Wistar rats were divided into four groups (<i>n</i> = 8): Group 1 (control), Group 2 (SM) received oral milk thistle (50 mg/kg/day) for 4 weeks, Group 3 (CuONPs) was intraperitoneally injected with CuONPs (50 mg/kg/day) for 3 weeks starting from day 7, and Group 4 (SM + CuONPs) received SM alone for one week then both SM and CuONPs for the next 3 weeks. Blood, bone marrow, liver, and kidney samples were collected for molecular, histopathological, immunohistochemical, and biochemical analyses. Group 3 showed DNA damage, reduced mitosis, and degeneration in liver and kidney tissues, along with increased expression of PCNA, Bax, and Cyclin D and elevated enzyme levels. In contrast, Group 4 (SM + CuONPs) exhibited notable improvement, with preserved tissue structure, reduced oxidative damage, and normalized enzymes. In conclusion, CuONPs induced genetic and organ toxicity, while <i>S. marianum</i> demonstrated a protective effect against these adverse outcomes.