Cyclophosphamide (CP) is an anti-neoplastic and immunosuppressive agent used in organ
transplantation and treatment of some autoimmune diseases. Melatonin (MT) has
immunomodulatory antioxidant effects. Omega-3 is an essential fatty acid used as an
antioxidant. The study aimed to compare the antioxidant role of MT versus omega-3 in the
pulmonary toxicity of cyclophosphamide in rats. Sixty male rats were divided into four equal
groups. Group Ι (Control group), Group ΙΙ: was given a single toxic dose of CP (200 mg/kg IP),
Group ΙΙΙ: was given a melatonin intraperitoneal (10mg/kg/day for two weeks) concomitantly
with CP and Group ΙV: was given fish oil through an intragastric tube (0.5 ml/kg/day for 2 weeks)
concomitantly with CP. Histological, immuno- histochemical and biochemical studies had done
to the rats' lungs. CP significantly induced oxidative lung damage. In Group ΙΙΙ and ΙV there were
significantly decreased lipid peroxidation and alterations in glutathione content (GSH),
superoxide dismutase (SOD) and catalase induced by CP in lung tissues. Histological
examination of the lungs in group II, revealed inflammatory cell infiltration with interstitial edema,
hemorrhage, septal thickening, which markedly reduced in groups III and IV (P< 0.05), but this
reduction was more marked with omega-3 (group IV). Also, groups III and IV, showed a
significant decrease (P< 0.05) in cellular infiltration and extravasated RBCs, collagen fibers
accumulation and in caspase-3 expression (P< 0.05) comparable to group II. Recommendation:
concomitant administration of omega-3with CP is essential as it over melatonin against CP
pulmonary toxicity.