Abstract: Background: 5-Fluorouracil (5-FU) is a chemotherapeutic agent that induces toxicity in several organs, especially nephrotoxicity and splenic injury. Aim: The aim of the study was to evaluate the ameliorative effects of Ziziphus spina-christi (ZSC) fruit extract on 5-FU-induced nephrotoxicity and splenic injury in male Wistar rats. Methodology: Rats were divided into four groups: control, 5-FU (150 mg/kg), and two ZSC pre-treatment groups (200 and 400 mg/kg/day) followed by 5-FU administration. Renal function parameters and spleen indices, oxidative stress indicators (MDA, SOD, CAT, GSH) as well as histopathology were measured. Results: 5-FU elevated serum creatinine (1.28±0.08 mg/dL) and BUN (68.5±4.2 mg/dL) significantly, which indicated severe renal dysfunction. It also increased the MDA significantly in the kidneys (48.7±2.5 nmol/mg protein) and spleen (39.1±2.1 nmol/mg protein) and seriously reduced the antioxidant enzymes (SOD, CAT) and GSH. There was widespread tubular necrosis in both kidneys and significant lymphoid depletion in spleens identified by histopathology. These adverse effects were mitigated by ZSC pre-treatment on a dose-dependent basis. A 400 mg/kg ZSC dose has almost normalized creatinine (0.52±0.04 mg/dL) and BUN (28.7±2.0 mg/dL) levels, ZSC significantly reduced MDA levels (kidney: 18.1±1.2; spleen: 16.9±1.0), in addition to restoring SOD, CAT, and GSH activities to control levels. Histologically, ZSC played a major role in preserving the renal and splenic architecture and decreased necrosis and lymphoid depletion and tissue destruction. Conclusion: Ziziphus spina-christi fruit extract is a a promising natural agent to counteract 5-FU-induced nephrotoxicity and splenic injury through the processes of improving antioxidant responses and tissue preservation.
Al-Jubori* et al. (Thu,) studied this question.