Mitigation of cyclophosphamide-induced hepatoxicity by Allium ampeloprasum Subsp Iranicum: A potential protective agent in chemotherapy

The liver is essential for drug metabolism and detoxification, and cyclophosphamide ( CP) can induce hepatotoxicity via oxidative stress and inflammatory responses. Allium ampeloprasum subsp. Iranicum harbors bioactive compounds with antioxidant and anti-inflammatory properties that may counteract CP-induced liver injury. The study aimed to investigate the hepatoprotective effect of A. ampeloprasum against CP-induced liver injury and to explore its underlying mechanisms. Mice were allocated into four groups: negative control, A. ampeloprasum alone, CP alone, and A. ampeloprasum combined with CP. Blood and tissue samples were collected and assessed for biochemical, histopathological, and molecular markers, including lipid peroxidation, antioxidant enzyme activity, and inflammatory cytokines. Post-treatment, aqueous extract of A. ampeloprasum significantly increased body weight versus control (p < 0.001), whereas CP reduced body weight versus control (p < 0.05). Liver weight was significantly reduced in the CP group compared to the control (p < 0.01), while no difference was observed between the A. ampeloprasum group and the control. Histopathology revealed normal morphology in control and A. ampeloprasum groups; CP induced marked hepatocellular damage with severe vacuolation, disrupted hepatic cords, and mild inflammation. A. ampeloprasum pretreatment before CP attenuated inflammation and restored architecture. CP significantly increased serum levels of aspartate aminotransferase (AST, +50.5 %), alanine aminotransferase (ALT, +107.7 %), and lactate dehydrogenase (LDH, +73.3 %), and decreased total protein (−8.5 %) and albumin (−37.3 %) vs control (P < 0.001). Thiobarbituric acid reactive substances (TBARS) rose > 4-fold with CP (P < 0.001) and were significantly attenuated by A. ampeloprasum (P < 0.001). Antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)) and pro-inflammatory cytokines (interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) were adversely modulated by CP and markedly ameliorated by A. ampeloprasum pretreatment (P range: 0.01–0.001). This study demonstrates that A. Ampeloprasum extract effectively mitigates CP-induced hepatotoxicity by reducing oxidative stress, inflammation, and tissue damage, indicating its potential as a natural protective agent during chemotherapy. Increased ( ↑ ) : • MAPK levels • γH2AX • MCP1 expression • Histopathological alterations • Oxidative stress • Inactivation of caspases-3 and −8 • Behavioral disorders • NFkB and pNFkB expressions Decreased (↓): Antioxidant enzyme activity p53, PUMA, and Drp-1 expressions • ampeloprasum mitigates CP-induced liver injury in mice. • Pretreatment lowers oxidative stress and inflammation markers. • Extract reduces IL-6, IL-1β, and TNF-α expression vs CP alone. • Potential natural protective agent during CP chemotherapy.