EFFECTS OF L-ARGININE ON CISPLATIN¬-INDUCED HEMATOLOGICAL CHANGES AND DYSLIPIDEMIA IN MALE WISTAR RATS

Student: Asonta Lois Ambrose
Supervisor: Prof Ajayi Ayodeji Folorunsho
HOD: Dr Bolaji Abosede Oreoluwa
Department of Physiology
Basic Medical Sciences
Adeleke University, Ede, Osun State

Abstract

ABSTRACT Background of Study: Cisplatin is a potent chemotherapeutic agent, that is limited by systemic toxicity affecting the kidneys, liver, and blood cells, causing anemia, leukopenia, thrombocytopenia, and dyslipidemia due to oxidative stress and inflammation. Recent studies highlight L-arginine's protective role, as it enhances nitric oxide production, counters oxidative damage, and improves immune and endothelial function. It performs this function by mitigating cisplatin-induced cytotoxicity, genotoxicity, and dyslipidemia by restoring antioxidant defenses and normalizing lipid metabolism. Aim: This study looks to evaluate the protective effect of L-arginine on hematological alterations and dyslipidemia induced by cisplatin in male Wistar rats. Methodology: Twenty-eight (28) male Wistar rats (150–250 g) were obtained from Adebare Animal Farms Owode-Ede. They were used for this study and housed under controlled conditions on 12:12hr light/dark cycle for 21 days. Rats were divided into four groups receiving distilled water orally, L-arginine (100 mg/kg) orally, Cisplatin (5 mg/kg) via intraperitoneal injection, and L-arginine orally + Cisplatin via intraperitoneal injection (100 mg/kg + 5 mg/kg). Blood was collected via retro-orbital puncture for hematological and biochemical assays. Hematological parameters were analyzed using a Sysmex XS 1000i analyzer, while lipid profile and oxidative stress markers were also assessed using standardized biochemical methods. Statistical analysis was performed using GraphPad Prism, Further analyses were done by one-way analysis of variance (ANOVA) followed by post hoc test (Bonferroni) with results expressed as mean ± SEM and significance set at p < 0.05. Results: L-Arginine significantly reversed cisplatin-induced toxicity in Wistar rats. Cisplatin increased erythropoietin, cholesterol, triglycerides, LDL, MDA, and decreased RBCs, WBCs, platelets, hemoglobin, HDL, SOD, CAT, GSH, and body weight. However, treatment with L- Arginine (100 mg/kg) reversed these changes, restoring hematological parameters, lipid profiles, antioxidant levels, and body weight towards normal values (p < 0.05). These findings suggest that L-Arginine possesses antioxidant, hematoprotective, and lipid-modulating properties offering protective effects against cisplatin-induced hematological, oxidative, lipid and weight disturbances in rats. Statistical analyses were done using one-way ANOVA and Bonferroni’s post hoc test. Conclusion: L-Arginine demonstrated protective effects against cisplatin-induced toxicity in Wistar rats by improving blood cell counts, stabilizing lipid profiles, and enhancing antioxidant activity. It helped mitigate oxidative stress and metabolic disruptions, suggesting its potential as a supportive agent to reduce cisplatin’s side effects during chemotherapy. Keywords: Cisplatin, L-Arginine, Hematological changes, Dyslipidemia, EPO, WBC, RBC, Hemoglobin, Platelets, CAT, SOD, MDA, GSH, Triglyceride, Total Cholesterol, HDL, and LDL.

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