Background and Objectives: GIfosfamide (IFO) is a highly effective chemotherapeutic agent used for treating a variety of cancer but has reported to cause certain side effects such as hepatotoxicity. Being antioxidant and anti-inflammatory agents, omega-3 fatty acids (ω3 FAs) were effective in the treatment of various medical conditions. This study aimed to elucidate the possible hepatoprotective role of ω3 FAs against IFO-induced liver injury. Methods and Results: A total of 42 adult male albino rats were divided into 4 groups; the control group (Gp I) of 12 rats, and 3 groups each of 10 rats. Omega-3 group (Gp II) received 300 mg/kg/day of omega-3 plus orally. IFO group (Gp III) received intraperitoneal injection of IFO 50 mg/kg, which was subdivided equally into IFO subgroup (Gp IIIa) and IFO recovery subgroup (Gp IIIb). IFO + Omega-3 group (Gp IV) received omega-3 plus as pretreatment and combined treatment with IFO. Liver sections were stained with Hematoxylin and Eosin (H&E), Periodic acid Schiff (PAS) and immunohistochemical stain for caspase-3. The mean area percent (%) of glycogen & optical density of immunopositive cells were measured. IFO had degenerative effects on rat hepatocytes with marked depletion of glycogen, inflammatory cells infiltration, dilatation and congestion of blood sinusoids, prominent Kupffer cells (KC), besides, a significant increase in caspase-3 immunoexpression. However, these alterations were far less pronounced in IFO + Omega-3 group. Conclusions: Administration of omega-3 FAs as a pretreatment and combined treatment with IFO ameliorated the liver injury induced by IFO indicating its hepatoprotective effects.

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