Bioactive Spirulina Protein Hydrolysate Mitigates Cyclophosphamide‐Induced Physiological, Biochemical, Histopathological, and Oxidative Stress Alterations in Rats

Chemotherapy‐induced toxicity remains a significant challenge in cancer treatment; natural product‐derived dietary supplements have attracted considerable attention as potential protective agents. Spirulina, a nutrient‐rich filamentous cyanobacterium widely used as a dietary supplement, is recognized for its antioxidant and anti‐inflammatory properties. Here, spirulina protein hydrolysate was evaluated for its protective effects against cyclophosphamide‐induced systemic toxicity in male Wistar rats aged 8 weeks at arrival. Following 1 week of acclimatization, rats were allocated to four groups ( n  = 6/group): normal control, cyclophosphamide control, and two hydrolysate‐treated groups. The hydrolysate was administered orally at 3 or 6 mg/kg body weight daily for 14 days, with cyclophosphamide (200 mg/kg body weight) injected intraperitoneally on Days 7 and 14. Histopathological examination used hematoxylin and eosin staining. Cyclophosphamide exposure was associated with lower body weight and sperm viability, whereas hydrolysate‐treated rats continued to gain weight and exhibited higher sperm viability than cyclophosphamide controls ( p < 0.05). Hydrolysate supplementation shifted selected serum biochemical parameters toward normal‐control values. Serum albumin concentrations were 2.52 ± 0.18 g/dL in cyclophosphamide controls and 3.62 ± 0.23 and 3.63 ± 0.37 g/dL in the 3 and 6 mg/kg hydrolysate groups, respectively (mean ± SD; both p < 0.05 vs. cyclophosphamide controls). Histopathological examination revealed cyclophosphamide‐associated damage in the liver, kidney, lung, testis, epididymis, seminal vesicle, and prostate gland. Hydrolysate‐treated groups, particularly the high‐dose group, showed better preservation of tissue architecture and fewer inflammatory and degenerative changes. These findings suggest that spirulina protein hydrolysate may mitigate selected cyclophosphamide‐associated physiological, biochemical, and histopathological alterations, providing preliminary preclinical evidence for its potential as a supportive dietary intervention.