L-Arginine Ameliorates Cyclophosphamide-Induced Toxicity Via Targeting Inflammatory Pathways and Oxidative Stress Mitigation

Abstract

Cyclophosphamide (CP)-induced toxicity was widely recognized previously. Therefore, L-Arginine, a compound with potent anti-inflammatory and antioxidant properties, was evaluated for its ability to ameliorate CP-related toxic changes in male albino rats. Twenty-eight mature male albino rats were divided into four groups (7 rats/each) and treated orally as follows: Group I functioned as the untreated control group, Group II received CP at a dose of 50 mg/kg body weight (B.Wt.), and Group III was treated with L-Arginine (L-Arg) (200 mg/kg B.Wt.), whereas Group IV was co-administered CP and L-Arg at the same previously stated doses. The treatment protocols were administered orally three times weekly for eight weeks. Among the hematological findings, leukopenia and thrombocytopenia were the most prominent alterations in the CP-treated group associated with increments in red blood cells (RBCs) count and hemoglobin (Hb) level. Moreover, the CP-exposed group exhibited significant elevations in serum hepatic enzyme activities, urea, creatinine, and cystatin-C concentrations with a significant decrement in serum testosterone level. Additionally, it showed marked elevations in serum levels of some inflammatory and oxidative markers such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and malondialdehyde (MDA) with marked decrease in catalase (CAT) activity and reduced glutathione (GSH) level. These biochemical alterations correlated histopathologically with multiple hepatic, renal, and testicular lesions, which were represented by inflammatory cell infiltration, vascular congestion, varying degrees of degeneration, and interstitial edema. L-Arg administration partially alleviated CP-induced hemato-biochemical disturbances and restored the histo-architecture of the affected organs. Overall, these results verified the multi-organ toxicity of CP and highlighted the mitigation effect of L-Arg against CP-induced hematological, biochemical, and histopathological alterations.