Systemic Toxicity Profile of Chemotherapeutic Agents in a Wistar Rat Model: A Preliminary Report

Chemotherapeutic agents are pivotal in cancer management, yet their utility is constrained by pronounced systemic and organ-specific toxicity, necessitating rigorous preclinical evaluation to enhance their safe application in oncology. This study examined the hematological, biochemical, electrolyte, and histopathological effects of seven chemotherapeutic drugs-docetaxel (10 mg/kg body weight), doxorubicin (10 mg/kg), paclitaxel (4 mg/kg), oxaliplatin (4 mg/kg), cisplatin (2 mg/kg), cytarabine (50 mg/kg), and cyclophosphamide (10 mg/kg)-and a phosphate-buffered saline (PBS) control (10 mL/kg) in male Wistar rats (n = 40, eight groups of five), adhering to the Organization for Economic Co-operation and Development (OECD) Guideline 425. Doses were selected based on established protocols from prior studies. Docetaxel induced leukocytosis and thrombocytosis, whereas doxorubicin and cisplatin elicited leukopenia and lymphopenia. Biochemical profiling revealed hepatotoxicity (elevated aminotransferase, alkaline phosphatase, and bilirubin) in rats treated with paclitaxel and cytarabine and nephrotoxicity (increased urea and creatinine) in those receiving paclitaxel and cyclophosphamide. Electrolyte analysis indicated hyperkaliemia with oxaliplatin, contrasted by hypokalemia with doxorubicin and cisplatin. Histopathological assessment of liver, kidney, spleen, and stomach tissues, stained with hematoxylin and eosin (H and E), revealed subacute, organ-specific alterations in rats administered cytarabine (50 mg/kg), cisplatin (2 mg/kg), doxorubicin (10 mg/kg), and cyclophosphamide (10 mg/kg) compared to the control (10 mL/kg), especially liver vacuolation and sinusoidal narrowing, kidney tubular flattening and glomerular compaction, spleen white pulp hypocellularity with red pulp congestion, and stomach submucosal inflammation with glandular hyperplasia. Notably, no necrosis or fibrosis was observed, suggesting potentially reversible effects. These findings highlight the heterogeneous toxicity profiles of chemotherapeutic agents, advocating for personalized monitoring and protective strategies in clinical practice to optimize therapeutic safety and efficacy.