Division of Nephrology and Hypertension Department of Medicine University of California-Irvine Orange CA.
Department of Internal Medicine Riverside Community Hospital University of California-Riverside School of Medicine Riverside CA.
Pharmacol Res Perspect. 2018 Feb 19;6(2):e00385. doi: 10.1002/prp2.385. eCollection 2018 Apr.
Tetrahydrocurcumin (THC) is the principal metabolite of curcumin and has antioxidant properties. In the present investigation, the effect of THC on renal and cardiovascular outcomes was studied in rats with chronic kidney disease (CKD). CKD rats were randomized following 5/6 nephrectomy to a special diet for 9 weeks which contained 1% THC (CKD+THC group). Low-dose polyenylphosphatidylcholine was used as a lipid carrier to increase bioavailability. Endpoints included tail blood pressure, normalized heart weight, plasma and urine biochemical data, and kidney tissue analyses. CKD animals demonstrated increased proteinuria, decreased creatinine clearance, hypertension, and cardiac hypertrophy. The antioxidant proteins CuZn SOD and glutathione peroxidase were decreased in the remnant kidney, while apoptosis (caspase-3) and fibrosis (alpha-SM actin) were increased. Renal fibrosis was confirmed histologically on trichrome staining. These pathologic changes were ameliorated in the CKD+THC group with significant decrease in proteinuria, hypertension, and kidney fibrosis. THC therapy restored levels of CuZn SOD and glutathione peroxidase. Consistent with prior reports, dietary THC did not improve nuclear Nrf2 levels. In summary, dietary THC therapy improved expression of antioxidant proteins in the remnant kidney, decreased renal fibrosis and proteinuria, and ameliorated hypertension in 5/6 nephrectomized rats.
四氢姜黄素（THC）是姜黄素的主要代谢物，具有抗氧化特性。在本研究中，研究了 THC 对慢性肾脏病（CKD）大鼠的肾脏和心血管结局的影响。5/6 肾切除术 9 周后，CKD 大鼠随机分为特殊饮食组，该饮食含有 1%的 THC（CKD+THC 组）。多烯磷脂酰胆碱的低剂量用作增加生物利用度的脂质载体。终点包括尾血压、校正的心脏重量、血浆和尿液生化数据以及肾脏组织分析。CKD 动物表现出蛋白尿增加、肌酐清除率降低、高血压和心脏肥大。抗氧化蛋白 CuZn SOD 和谷胱甘肽过氧化物酶在残肾中减少，而细胞凋亡（半胱氨酸天冬氨酸蛋白酶-3）和纤维化（α-SM 肌动蛋白）增加。在三原色染色的组织学上证实了肾纤维化。这些病理变化在 CKD+THC 组得到改善，表现为蛋白尿、高血压和肾脏纤维化显著减少。THC 治疗恢复了 CuZn SOD 和谷胱甘肽过氧化物酶的水平。与之前的报道一致，饮食 THC 并未改善核 Nrf2 水平。总之，饮食 THC 治疗改善了残肾中抗氧化蛋白的表达，减少了肾纤维化和蛋白尿，并改善了 5/6 肾切除大鼠的高血压。
