Mishra Pooja, Ahsan Farogh, Mahmood Tarique, Bano Shahzadi, Ansari Vaseem Ahamad, Yadav Jyoti, Ansari Jamal Akhtar, Khan Mohd Masih Uzzaman
Department of Pharmacy, Integral University, Lucknow, India.
Department of Chemistry, Integral University, Lucknow, India.
J Appl Toxicol. 2025 Oct;45(10):2020-2041. doi: 10.1002/jat.4822. Epub 2025 May 30.
α-Arbutin, a glucoside of hydroquinone, is utilized as a skin-lightening agent that inhibits human tyrosinase activity. Although it exhibits antioxidant and anti-inflammatory properties, limited research exists on its toxicological effects. This research investigates the oral toxicity of α-arbutin in both acute and subacute settings using Sprague-Dawley rats as test subjects. Female Sprague-Dawley rats underwent acute oral toxicity testing in accordance with OECD TG 425 guidelines. The rats received oral doses of 175, 550, 1750, and 2000 mg/kg. Additionally, a subacute oral toxicity study following OECD TG 407 protocols was performed on both male and female rats. In this study, the animals were given daily oral doses of 250, 500, 1000, and 2000 mg/kg for 28 days. During acute and subacute oral toxicity assessments, no deaths or observable changes in behavior were noted at the administered doses. Examination of gross anatomy showed a significant decrease in the relative spleen weight of rats given α-arbutin at 250 mg/kg compared to the control group. Male rats treated with α-arbutin exhibited markedly non-significantly increased levels of AST, ALT, and chloride ions. In contrast, mean corpuscular hemoglobin concentration levels notably decreased at lower α-arbutin doses relative to the control group. Brain histopathology of male rats revealed moderate inflammation with pyknotic nuclei, whereas the cortex showed extensive epithelial cell necrosis following the administration of 2000 mg/kg of α-arbutin. The results showed that when given for a short time, α-arbutin is nontoxic till 2000 mg/kg. The median lethal dose (LD) of α-arbutin is more than 2000 mg/kg. A long-term toxicity study may be performed to validate the result. This study evaluated the acute and subacute oral toxicity of α-arbutin in Sprague-Dawley rats. No mortality or significant behavioral changes were observed up to 2000 mg/kg. However, at higher doses, male rats exhibited elevated liver enzymes and chloride ions, along with brain inflammation and cortical necrosis. Overall, α-arbutin showed no remarkable toxicity at tested doses, with an LD exceeding 2000 mg/kg, warranting further long-term safety assessments.
α - 熊果苷是对苯二酚的一种糖苷，用作抑制人类酪氨酸酶活性的美白剂。尽管它具有抗氧化和抗炎特性，但关于其毒理学效应的研究有限。本研究以Sprague - Dawley大鼠为实验对象，调查α - 熊果苷在急性和亚急性情况下的口服毒性。雌性Sprague - Dawley大鼠按照经合组织TG 425指南进行急性口服毒性试验。大鼠接受175、550、1750和2000mg/kg的口服剂量。此外，按照经合组织TG 407方案对雄性和雌性大鼠进行了亚急性口服毒性研究。在本研究中，动物连续28天每天接受250、500、1000和2000mg/kg的口服剂量。在急性和亚急性口服毒性评估期间，在所给予的剂量下未观察到死亡或行为上的明显变化。大体解剖检查显示，与对照组相比，给予250mg/kgα - 熊果苷的大鼠脾脏相对重量显著降低。用α - 熊果苷处理的雄性大鼠的天冬氨酸转氨酶、丙氨酸转氨酶和氯离子水平明显升高，但无显著统计学意义。相比之下，较低剂量的α - 熊果苷组平均红细胞血红蛋白浓度水平相对于对照组显著降低。雄性大鼠的脑组织病理学显示有中度炎症伴核固缩，而在给予2000mg/kgα - 熊果苷后，皮质出现广泛的上皮细胞坏死。结果表明，短期内给予α - 熊果苷，直至2000mg/kg时无毒。α - 熊果苷的半数致死剂量（LD）超过2000mg/kg。可能需要进行长期毒性研究以验证该结果。本研究评估了α - 熊果苷对Sprague - Dawley大鼠的急性和亚急性口服毒性。在高达2000mg/kg的剂量下未观察到死亡或显著的行为变化。然而，在较高剂量下，雄性大鼠表现出肝酶和氯离子升高，以及脑部炎症和皮质坏死。总体而言，α - 熊果苷在测试剂量下未显示出明显毒性，LD超过2000mg/kg，需要进一步进行长期安全性评估。
