Krishnaraj Prithvika, Ravindran Sriram, Kurian Gino A
School of Chemical and Biotechnology, Sastra University, Thanjavur, India.
Vascular Biology Lab, Sastra University, Thanjavur, 613401, India.
Int Urol Nephrol. 2016 Nov;48(11):1927-1935. doi: 10.1007/s11255-016-1375-z. Epub 2016 Jul 27.
Vascular calcification (VC) is an impact of calcium accumulation in end-stage renal diseases, normally initiated in the mitochondria. Sodium thiosulfate (STS) is effective in rescuing mitochondrial function in the neurovascular complications associated with VC, but has limitation in protecting the cardiac mitochondria. However, the STS efficacy in restoring the renal mitochondrial function has not been studied, which is the primary focus of this study.
Wistar rats (n = 6/group) were administered 0.75 % adenine in the diet for 28 days to induce renal failure. STS (400 mg/kg) was given in two regimens STS_Pre (preventive: along with adenine for 28 days) and STS_Cur (curative: 29th to 49th day). Renal failure was assessed by plasma and urinary markers. The effectiveness of treatment was assessed from oxidative stress, DNA damage, mitochondrial physiology and enzymology in the renal tissue.
0.75 % adenine diet caused renal medullary swelling, tubular interstitial nephropathy and impaired renal function (creatinine, urea, uric acid and ALP), which were recovered after STS treatment. The renal failure was due to oxidative stress as measured by elevated malondialdehyde (29 %) and lowered reduced glutathione (27 %) levels. STS reduced the lipid peroxidation and significantly (p < 0.05) elevated the antioxidant enzymes. Further, it improved renal mitochondrial respiratory capacity by maintaining the hyperpolarized membrane potential and restored the complex enzyme activities. Absence of renal DNA fragmentation supports the above findings.
STS protects the kidney by preserving renal mitochondria, in experimental adenine-induced vascular calcified rats. The efficacy was prominent when given after induction, i.e., in STS_Cur group.
血管钙化（VC）是终末期肾病中钙积累的一种表现，通常始于线粒体。硫代硫酸钠（STS）可有效挽救与VC相关的神经血管并发症中的线粒体功能，但在保护心脏线粒体方面存在局限性。然而，STS恢复肾线粒体功能的功效尚未得到研究，这是本研究的主要重点。
将Wistar大鼠（每组n = 6）在饮食中给予0.75%腺嘌呤，持续28天以诱导肾衰竭。STS（400 mg/kg）以两种方案给药，即STS_Pre（预防性：与腺嘌呤一起给药28天）和STS_Cur（治疗性：第29天至第49天）。通过血浆和尿液标志物评估肾衰竭。从肾组织中的氧化应激、DNA损伤、线粒体生理学和酶学方面评估治疗效果。
0.75%腺嘌呤饮食导致肾髓质肿胀、肾小管间质性肾病和肾功能受损（肌酐、尿素、尿酸和碱性磷酸酶），STS治疗后这些症状得到恢复。肾衰竭是由氧化应激引起的，表现为丙二醛水平升高（29%）和还原型谷胱甘肽水平降低（27%）。STS减少了脂质过氧化，并显著（p < 0.05）提高了抗氧化酶的水平。此外，它通过维持超极化膜电位改善了肾线粒体呼吸能力，并恢复了复合酶活性。肾DNA片段化的缺失支持了上述发现。
在实验性腺嘌呤诱导的血管钙化大鼠中，STS通过保护肾线粒体来保护肾脏。诱导后给药时，即STS_Cur组，疗效显著。
