Time-dependent protective effects of Silymarin on renal Ischemia-reperfusion injury in rats

Objective: Renal ischemia–reperfusion (I/R) injury is a major cause of acute kidney injury observed in surgical and clinical settings such as shock, trauma, partial nephrectomy, and renal transplantation. This study aimed to evaluate the protective effects of silymarin, a flavonolignan complex extracted from Silybum marianum (milk thistle), against renal I/R injury at varying ischemia durations in rats. Materials and methods: Forty-eight adult male Wistar albino rats were randomly divided into eight groups (n=6 each). The sham group underwent laparotomy only. Control I/R groups were subjected to 45, 60, or 90 minutes of ischemia followed by 180 minutes of reperfusion. Silymarin-treated groups received 100 mg/kg/day silymarin orally for seven days before surgery and underwent the same I/R protocols. At the end of reperfusion, renal tissues and blood samples were collected to determine total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), and malondialdehyde (MDA) levels. Histopathological evaluation was performed on hematoxylin–eosin–stained sections. Results: The highest serum TAS and SOD levels were observed in the SIL 45 group, indicating a strong early antioxidant response to silymarin. Serum and tissue MDA levels, indicators of lipid peroxidation, were significantly lower in silymarin-treated groups than in corresponding I/R groups. However, the protective effect decreased as ischemia duration increased. Histopathological analysis revealed less tubular necrosis, vacuolar degeneration, and interstitial congestion in silymarin-treated groups, particularly at shorter ischemia durations. Conclusion: Silymarin exerts a significant renoprotective effect by enhancing antioxidant capacity and reducing oxidative stress in renal I/R injury. Nevertheless, its efficacy diminishes with prolonged ischemia, suggesting a time-dependent limitation in protection.