Toxicological Assessment of Ethanol Extract of Ficus exasperata and Sida acuta leaves in Alloxan-induced Diabetic Rats

Background: The mechanism of diabetes mellitus involves oxidative stress, which damages cells, tissues, and organs and predisposes affected individuals to complications such as nephropathy, hepatotoxicity, and cardiovascular disease. Interestingly, combining therapeutic agents that target multiple biochemical pathways, including antioxidant, anti-inflammatory, and metabolic mechanisms, may yield better outcomes than monotherapy. The adverse effects associated with some conventional antidiabetic drugs have also increased interest in plant-based therapies with organ-protective potentials. Aim: This study evaluated the toxicological effects of ethanol extracts of Ficus exasperata and Sida acuta, administered singly and in combination, in alloxan-induced diabetic rats. Study Design: Experimental animal study involving acute toxicity testing and a 28-day antidiabetic treatment in alloxan-induced diabetic Wistar rats. Place and Duration of Study: Department of Applied Biochemistry, Faculty of Biosciences, Nnamdi Azikiwe University, Awka, and Chris Experimental Animal Farm and Research Laboratory, Awka, Nigeria. The duration of treatment was 28 days. Methodology: Acute oral toxicity (LD50) was evaluated using Lorke’s method. One hundred and four (104) male Wistar rats were used for the acute toxicity study, while 63 female Wistar albino rats were used for the antidiabetic study and divided into nine groups (n = 7). Diabetes was induced with alloxan monohydrate (150 mg/kg, intraperitoneally). After 28 days of treatment, serum liver function markers, renal function indices, and electrolyte parameters were determined using standard spectrophotometric and diagnostic methods. Results: The LD50 of the ethanol extract of Sida acuta was 2154 mg/kg body weight, while that of Ficus exasperata was 3808 mg/kg body weight. Untreated diabetic rats showed significant increases in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, urea, and creatinine concentrations compared to the normal control. Treatment with the single and combined extracts improved these parameters compared with the untreated diabetic group. The extracts also improved the electrolyte imbalance. Conclusion: The ethanol extracts of Sida acuta and Ficus exasperata leaves showed protective effects against diabetes induced hepatic and renal dysfunction, with evidence of improved biochemical and electrolyte parameters when administered singly or in combination. These findings support the safety and ethnomedicinal relevance of both plants.