Acute Toxicity Test of Pomegranate (Punica granatum L.) Peel ExtractNanogel on the Liver and Kidneys of Wistar Rats

Introduction: Periodontal disease is a chronic inflammatory condition of the supporting tissues of the teeth causedprimarily by biofilm-associated microbial infection. With a high global prevalence—including 74.1% in Indonesia as of2022—conventional treatment relying on mechanical therapy and synthetic drugs often faces challenges such as adverseeffects and the development of antibiotic resistance. As a safer alternative, herbal therapies using pomegranate (Punicagranatum L.) peel extract, rich in bioactive compounds like flavonoids, tannins, and punicalagin, offer antioxidant,antibacterial, and anti-inflammatory benefits. However, safety evaluations, including acute toxicity testing, are essentialprior to clinical application, especially in nanogel formulations designed for topical use.Materials and methods: This laboratory-based experimental study used a post-test control group design involving 30female Wistar rats, divided into one control group (0.5% Na-CMC) and four treatment groups receiving nanogel doses of5, 50, 300, and 2000 mg/kg BW (BW). Parameters assessed included clinical signs of toxicity, mortality, body weightchanges, organ weights, macroscopic appearance of the liver and kidneys, serum levels of creatinine, ALT, and AST, aswell as histopathological evaluations of the liver and kidneys.Results: No mortality or significant toxic symptoms were observed throughout the 14-day observation period. There wereno statistically significant differences (p > 0.05) in body weight, relative organ weights, or biochemical markers (creatinine,ALT, AST) between the treatment and control groups. Histopathological analysis showed normal liver architecture acrossall groups, while mild inflammation in renal tissue was observed only at the highest dose (2000 mg/kg BW).Conclusion: The administration of pomegranate peel extract nanogel up to a dose of 2000 mg/kg BW resulted in nosystemic toxicity and only mild, non-lethal renal inflammation. These findings suggest that the formulation is well-toleratedin acute exposure and may be considered safe for further development as a topical adjunctive therapy in periodontaltreatment.