Cyanotoxins are a significant concern due to their frequent presence in Southamerica waters. While numerous studies have investigated the toxic effects of MC-LR, knowledge regarding the toxicity of [D-Leu¹]MC-LR remains limited. The aim of this study was to determine the impact of [D-Leu¹]MC-LR and MC-LR administration on different brain structures in rats and the resulting modifications in oxidative stress. Male Sprague-Dawley rats were divided into two groups and administered 5 intraperitoneal injections of mixed MCs at doses of 2 and 15 µg kg^-1 for each injection over a 21-day period, i.e. total doses of 10 and 75 µg kg^-1.The MCs consisted on MC-LR (3 %), [D-Leu¹]MC-LR (96.7 %) and others (0.3 %) isoforms. To evaluate the effect of treatments with different doses, the concentration of both MC isoforms, reactive oxygen species (ROS), lipid damage and antioxidant activity were measured in the cerebral cortex, hippocampus, striatum and cerebellum. The results revealed variability in MC concentration across brain regions. The accumulation rate of MC-LR was 2000 times higher than that of [D-Leu¹]MC-LR, regardless of the dose administered at different areas. Taken together, our results highlighted that chronic exposure to MCs induced a mild oxidative stress in the rat brain characterized by increased ROS and antioxidant defense activation due to [D-Leu¹]MC-LR in both the striatum and cortex at high dose. At low dose, the uptake of only MC-LR was determined in the cerebellum and hippocampus, resulting in increased ROS levels but no change in CAT activity in the hippocampus. In contrast, in the cerebellum, there was a decrease in ROS, possibly due to increased CAT consumption. However, the absence of detection of an MC variant under certain conditions does not allow for the exclusion of its metabolic effects. Chronic MC administration resulted in dose- and region-dependent distribution within the rat brain. Reactive species levels and cellular responses also varied by dose and region.

Keywords: Antioxidant capacity; Microcystins; Oxidative stress; Rat brain; [D-Leu1]MC-LR.

© 2025 The Authors. Published by Elsevier B.V.

蓝藻毒素由于在南美水域中的频繁存在而成为一个重要的问题。虽然有许多研究调查了MC-LR（微囊藻毒素-莱因）的毒性作用，但对于[D-Leu¹]MC-LR毒性的了解仍然有限。本研究旨在确定[D-Leu¹]MC-LR和MC-LR给药对大鼠不同脑结构的影响以及由此产生的氧化应激变化。实验将雄性Sprague-Dawley大鼠分为两组，并在21天内每只老鼠接受了5次腹腔注射混合微囊藻毒素，剂量分别为每次注射2 µg kg^-1 和 15 µg kg^-1 ，即总剂量为10 µg kg^-1和75 µg kg^-1。这些微囊藻毒素由3%的MC-LR、96.7%的[D-Leu¹]MC-LR和其他等位基因形式（0.3%）组成。为了评估不同剂量治疗的效果，测量了大脑皮质、海马体、纹状体和小脑中的两种微囊藻毒素异构体浓度、活性氧(ROS)水平、脂质损伤及抗氧化能力的变化。结果显示，在不同的脑区域中存在MC浓度的差异性变化。无论在给药的不同区域，MC-LR的积累速率比[D-Leu¹]MC-LR高2000倍。综合来看，我们的结果表明慢性暴露于微囊藻毒素会导致大鼠大脑出现轻度氧化应激，表现为ROS水平升高和抗氧化防御激活，特别是在纹状体和皮质中的高剂量情况下的[D-Leu¹]MC-LR。在低剂量情况下，在小脑和海马中只检测到MC-LR的摄取量增加，但仅在海马体内CAT（过氧化氢酶）活性未见变化，而在ROS水平上升。相比之下，在小脑内观察到了ROS水平下降的现象，可能是由于CAT消耗增多所致。然而，特定条件下无法检出某一种微囊藻毒素变体，并不能排除其代谢效应的存在。慢性给予MC会导致大鼠大脑中剂量和区域依赖性的分布。反应性物种的浓度及细胞响应也表现出剂量与区域差异。

关键词：

抗氧化能力；微囊藻毒素；氧化应激；大鼠脑；[D-Leu¹]MC-LR。

© 2025 The Authors. Published by Elsevier B.V.