Modulatory Role of Saroglitazar on Novel Hematological Inflammatory Ratios and Metabolic Parameters in Animal Model of 5-Fluorouracil Toxicity

Hani Hadi Mohammed; Roza Haroon Rasheed; Tavga Ahmed Aziz

doi:10.54133/ajms.v10i2.2325

Authors

Hani Hadi Mohammed Department of Basic Medical Sciences, College of Medicine, University of Sulaimani, Kurdistan Region, Iraq https://orcid.org/0009-0007-2198-2655
Roza Haroon Rasheed Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq https://orcid.org/0009-0005-2198-3418
Tavga Ahmed Aziz Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Kurdistan Region, Iraq https://orcid.org/0000-0003-2742-6127

DOI:

https://doi.org/10.54133/ajms.v10i2.2325

Keywords:

Chemotherapy-induced toxicity, 5-FU, Hematological inflammatory ratios, Saroglitazar

Abstract

Background: 5-Fluorouracil (5-FU), a widely used chemotherapeutic agent, causes oxidative stress, inflammation, and multi-organ damage, particularly cardiotoxicity. Saroglitazar, a dual peroxisome proliferator-activated receptor α/γ agonist with lipid-lowering, insulin-sensitizing, and anti-inflammatory effects, may ameliorate these adverse outcomes. Objective: To evaluate how saroglitazar influences hematological inflammatory ratios and metabolic parameters in a rat model of 5-fluorouracil-induced toxicity. Methods: 35 adult males Wistar rats were categorized into five groups: Control (NC), 5-FU-treated positive control (PC), N-acetylcysteine (NAC) (100mg/kg) + 5-FU, SAR low (0.5mg/kg)+5-FU, and SAR high (5.0mg/kg)+5-FU. 150mg/kg 5-FU was given intraperitoneally on the 10th day of treatment. Biochemical markers were evaluated, including cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), glucose, and HbA1c; inflammatory markers such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR); and hematological markers such as hemoglobin concentration (Hb), red blood cell count (RBC), and white blood cell count (WBC). Results: 5-FU treatment caused significant metabolic alteration, including dyslipidemia, hyperglycemia, systemic inflammation, and hematological suppression. Saroglitazar, on the other hand, improved lipid profiles by reducing cholesterol, triglycerides, and LDL and showed a glucose-lowering effect. It also reduced NLR and MLR, demonstrating their superior anti-inflammatory activity. Saroglitazar also improved RBC count and Hb levels, indicating its influence on erythropoiesis and bone marrow function. Conclusion: Saroglitazar mitigates 5-fluorouracil-induced metabolic, inflammatory, and hematological disturbances, supporting its potential as an adjunct to chemotherapy. Assessing its long-term effectiveness and practical use is recommended.

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