Eiam-Ong Somchit, Nakchui Yuyen, Chaipipat Mookda, Eiam-Ong Somchai
Department of Physiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
School of Medicine, Walailak University, Nakhonsrithammarat, Thailand.
Toxicol Res. 2018 Apr;34(2):143-150. doi: 10.5487/TR.2018.34.2.143. Epub 2018 Apr 15.
It has been demonstrated that vanadate causes nephrotoxicity. Vanadate inhibits renal sodium potassium adenosine triphosphatase (Na, K-ATPase) activity and this is more pronounced in injured renal tissues. Cardiac cyclic adenosine monophosphate (cAMP) is enhanced by vanadate, while increased cAMP suppresses Na, K-ATPase action in renal tubular cells. There are no data collectively demonstrating the effect of vanadate on renal cAMP levels; on the abundance of the alpha 1 isoform (α) of the Na, K-ATPase protein or its cellular localization; or on renal tissue injury. In this study, rats received a normal saline solution or vanadate (5 mg/kg BW) by intraperitoneal injection for 10 days. Levels of vanadium, cAMP, and malondialdehyde (MDA), a marker of lipid peroxidation were measured in renal tissues. Protein abundance and the localization of renal α-Na, K-ATPase was determined by Western blot and immunohistochemistry, respectively. Renal tissue injury was examined by histological evaluation and renal function was assessed by blood biochemical parameters. Rats treated with vanadate had markedly increased vanadium levels in their plasma, urine, and renal tissues. Vanadate significantly induced renal cAMP and MDA accumulation, whereas the protein level of α-Na, K-ATPase was suppressed. Vanadate caused renal damage, azotemia, hypokalemia, and hypophosphatemia. Fractional excretions of all studied electrolytes were increased with vanadate administration. These findings demonstrate that vanadate might suppress renal α-Na, K-ATPase protein functionally by enhancing cAMP and structurally by augmenting lipid peroxidation.
已证实钒酸盐会导致肾毒性。钒酸盐会抑制肾钠钾三磷酸腺苷酶（Na，K - ATPase）的活性，且在受损肾组织中这种抑制作用更为明显。钒酸盐会使心脏环磷酸腺苷（cAMP）增加，而cAMP增加会抑制肾小管细胞中的Na，K - ATPase活性。目前尚无数据能全面证明钒酸盐对肾cAMP水平、Na，K - ATPase蛋白α1亚型（α）的丰度或其细胞定位，以及对肾组织损伤的影响。在本研究中，大鼠通过腹腔注射接受生理盐水或钒酸盐（5 mg/kg体重），持续10天。测定肾组织中钒、cAMP和脂质过氧化标志物丙二醛（MDA）的水平。分别通过蛋白质印迹法和免疫组织化学法测定肾α - Na，K - ATPase的蛋白丰度和定位。通过组织学评估检查肾组织损伤，并通过血液生化参数评估肾功能。用钒酸盐处理的大鼠血浆、尿液和肾组织中的钒水平显著升高。钒酸盐显著诱导肾cAMP和MDA积累，而α - Na，K - ATPase的蛋白水平受到抑制。钒酸盐导致肾损伤、氮质血症、低钾血症和低磷血症。给予钒酸盐后，所有研究电解质的分数排泄量均增加。这些发现表明，钒酸盐可能通过增强cAMP在功能上抑制肾α - Na，K - ATPase蛋白，并通过增加脂质过氧化在结构上抑制该蛋白。
