Abstract
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from impaired insulin secretion, insulin action, or both, and it is associated with severe microvascular and macrovascular complications. Despite the availability of several antidiabetic drugs, long-term therapy is often limited by adverse effects, reduced efficacy, high cost, and failure to prevent disease progression, highlighting the need for novel therapeutic strategies. Drug repurposing has emerged as an effective approach to identify new pharmacological uses for existing drugs with established safety profiles. Streptozotocin-induced diabetic rat models are widely used in experimental research due to their ability to mimic pancreatic ?-cell destruction, oxidative stress, and metabolic abnormalities observed in human diabetes, making them suitable for preclinical evaluation of antidiabetic agents. Atovaquone, a hydroxynaphthoquinone derivative primarily used as an antiprotozoal and antimicrobial agent, has gained recent scientific interest for its potential metabolic and cytoprotective effects. Its ability to modulate mitochondrial electron transport, reduce oxidative stress, and influence cellular energy metabolism provides a strong rationale for exploring its antidiabetic potential. This review aims to critically evaluate the antidiabetic activity of Atovaquone in streptozotocin-induced diabetic rats by summarizing available preclinical evidence related to its effects on blood glucose levels, insulin sensitivity, lipid profile, oxidative stress markers, inflammatory mediators, and pancreatic histopathology. The findings from experimental studies suggest that Atovaquone may exert significant antihyperglycemic and antioxidant effects, contributing to improved metabolic control in diabetic conditions. However, further mechanistic investigations and well-designed clinical studies are necessary to validate these findings and establish its therapeutic relevance in diabetes management. This review highlights the potential of Atovaquone as a promising repurposed candidate for future antidiabetic drug development.
Keywords
Diabetes mellitus, Atovaquone, Streptozotocin, Drug repurposing, Antidiabetic activity
Introduction
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The disease has reached epidemic proportions globally, affecting an estimated 537 million adults worldwide, a number projected to rise to 643 million by 2030 according to the International Diabetes Federation (IDF) [1]. The pathophysiology of diabetes mellitus involves disturbances in carbohydrate, lipid, and protein metabolism, often accompanied by oxidative stress, chronic inflammation, and endothelial dysfunction [2]. Chronic hyperglycemia leads to severe complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases, significantly increasing morbidity and mortality rates among affected individuals [3]. Despite the availability of several pharmacological interventions including insulin, sulfonylureas, biguanides, thiazolidinediones, and DPP-4 inhibitors, the effective management of diabetes remains a major challenge. Many of these agents exhibit limited efficacy over time and are associated with undesirable side effects such as hypoglycemia, weight gain, and gastrointestinal disturbances [4,5]. Consequently, there is a continuous need to explore new therapeutic strategies, including the repurposing of existing drugs with favorable safety profiles for novel indications [6]. Experimental animal models play a pivotal role in diabetes research by providing valuable insights into disease mechanisms and facilitating the evaluation of potential antidiabetic agents before clinical translation. Among these, rodent models are most widely used due to their physiological similarity to humans, reproducibility, and well-characterized metabolic pathways [7]. Atovaquone, a hydroxy-naphthoquinone derivative primarily used as an antimalarial and antipneumocystis agent, has recently garnered attention for its pleiotropic pharmacological properties beyond antiparasitic activity [8]. It exhibits potent antioxidant, anti-inflammatory, and mitochondrial modulatory effects, which may contribute to its potential antidiabetic efficacy [9]. Given the involvement of oxidative stress and mitochondrial dysfunction in diabetes pathogenesis, exploring Atovaquone’s effect on glucose metabolism and pancreatic β-cell protection in experimental diabetic models is scientifically justified. Therefore, investigating the antidiabetic potential of Atovaquone against streptozotocin (STZ)-induced diabetic rats may provide novel insights into drug repurposing for metabolic disorders [10].
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Rushikesh Kale
Corresponding author
M. Pharm, Department of pharmacology, Anuradha College of Pharmacy Chikhali, Buldhana, Maharashtra, India.
Deepak Ambhore
Co-author
Assoc. Prof. M. Pharm, Department of Pharmaceutics, Anuradha College of Pharmacy Chikhali, Buldhana, Maharashtra, India.
Dr. G. V. Bihani
Co-author
Assoc. Prof. M. Pharm PhD, Department of pharmacology, Anuradha College of Pharmacy Chikhali, Buldhana, Maharashtra, India.
Dr. K. R. Biyani
Co-author
Principal, M. Pharm PhD, Department of pharmacology, Anuradha College of Pharmacy Chikhali, Buldhana, Maharashtra, India.
Rushikesh Kale*, Deepak Ambhore, Dr. G. V. Bihani, Dr. K. R. Biyani, Exploring the Antidiabetic Potential of Atovaquone: Insights from Streptozotocin-Induced Diabetic Rat Models, Int. J. Sci. R. Tech., 2026, 3 (2), 27-35. https://doi.org/10.5281/zenodo.18472891
10.5281/zenodo.18472891
