Hitsuda Yuuka, Koto Yoshihito, Kawahara Hideaki, Kurata Koichi, Yoshikiyo Keisuke, Nishimura Kohji, Hashiguchi Ayumi, Maseda Hideaki, Okano Kunihiro, Sugiura Norio, Shimizu Kazuya, Shimizu Hidehisa
Graduate School of Natural Science and Technology, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan.
Graduate School of Life and Environmental Science, Shimane University, 1060 Nishikawatsu-Cho, Matsue 690-8504, Japan.
Toxics. 2024 Jul 27;12(8):547. doi: 10.3390/toxics12080547.
Toxic algae in eutrophic lakes produce cyanotoxic microcystins. Prior research on the effect of microcystin-LR in the kidney utilized intraperitoneal injections, which did not reflect natural exposure. Oral microcystin-LR research has focused on renal function and histopathology without examining the molecular mechanisms. The present study aimed to evaluate the mechanism of microcystin-LR in the kidneys via oral administration in WKAH/HkmSlc rats over 7 weeks, alongside stimulation of the proximal tubular cells. Although there were no differences in the concentrations of plasma albumin, blood urea nitrogen, and creatinine, which are parameters of renal function, between the control and microcystin-LR-administrated rats, expression was significantly increased in the renal cortex of the rats administered microcystin-LR and the microcystin-LR-treated proximal tubular cells. The expression levels of (), (), and () in the renal cortex did not differ significantly between the control and microcystin-LR-administered rats. However, the expression levels of were significantly positively correlated with those of , , and in the renal cortex of rats administered microcystin-LR. Additionally, a significant positive correlation was observed between the expression levels of and . Collectively, increased expression caused by the long-term consumption of microcystin-LR may initiate a process that influences renal fibrosis and abnormal renal function by regulating the expression levels of , , and .
富营养化湖泊中的有毒藻类会产生蓝藻毒素微囊藻毒素。先前关于微囊藻毒素-LR对肾脏影响的研究采用腹腔注射，这无法反映自然暴露情况。口服微囊藻毒素-LR的研究主要集中在肾功能和组织病理学方面，而未研究分子机制。本研究旨在通过对WKAH/HkmSlc大鼠进行为期7周的口服给药，并刺激近端肾小管细胞，来评估微囊藻毒素-LR在肾脏中的作用机制。虽然对照组和给予微囊藻毒素-LR的大鼠在血浆白蛋白、血尿素氮和肌酐（这些都是肾功能参数）的浓度上没有差异，但在给予微囊藻毒素-LR的大鼠肾皮质以及经微囊藻毒素-LR处理的近端肾小管细胞中， 表达显著增加。对照组和给予微囊藻毒素-LR的大鼠肾皮质中 、 和 的表达水平没有显著差异。然而，在给予微囊藻毒素-LR的大鼠肾皮质中， 的表达水平与 、 和 的表达水平显著正相关。此外，观察到 和 的表达水平之间存在显著正相关。总体而言，长期摄入微囊藻毒素-LR导致的 表达增加可能通过调节 、 和 的表达水平引发一个影响肾纤维化和肾功能异常的过程。
