Pathology Department, University at Buffalo, Buffalo, New York, USA.
Division of Nephrology, Department of Medicine, University of California, Irvine, California, USA.
Pharmacol Res Perspect. 2023 Apr;11(2):e01079. doi: 10.1002/prp2.1079.
Tetrahydrocurcumin (THC), a principal metabolite of curcumin, was tested in a rat model of type 2 diabetes mellitus. THC was administered via daily oral gavage with the lipid carrier polyenylphosphatidylcholine (PPC) as add-on therapy to losartan (angiotensin receptor blocker) to examine effects on kidney oxidative stress and fibrosis. A combination of unilateral nephrectomy, high-fat diet and low-dose streptozotocin was used to induce diabetic nephropathy in male Sprague-Dawley rats. Animals with fasting blood glucose >200 mg/dL were randomized to PPC, losartan, THC + PPC or THC + PPC + losartan. Untreated chronic kidney disease (CKD) animals had proteinuria, decreased creatinine clearance, and evidence of kidney fibrosis on histology. THC + PPC + losartan treatment significantly lowered blood pressure concurrent with increased messenger RNA levels of antioxidant copper-zinc-superoxide dismutase and decreased protein kinase C-α, kidney injury molecule-1 and type I collagen in the kidneys; there was decreased albuminuria and a trend for increased creatinine clearance compared to untreated CKD rats. There was decreased fibrosis on kidney histology in PPC-only and THC-treated CKD rats. Plasma levels of kidney injury molecule-1 were decreased in THC + PPC + losartan animals. In summary, add-on THC to losartan therapy improved antioxidant levels and decreased fibrosis in the kidneys, and lowered blood pressure in diabetic CKD rats.
四氢姜黄素（THC）是姜黄素的主要代谢产物，在 2 型糖尿病大鼠模型中进行了测试。通过每日口服脂质载体多烯磷脂酰胆碱（PPC）给予 THC 作为洛沙坦（血管紧张素受体阻滞剂）的附加治疗，以检查其对肾脏氧化应激和纤维化的影响。单侧肾切除术、高脂肪饮食和小剂量链脲佐菌素联合使用，诱导雄性 Sprague-Dawley 大鼠发生糖尿病肾病。空腹血糖>200mg/dL 的动物随机分为 PPC、洛沙坦、THC+PPC 或 THC+PPC+洛沙坦。未经治疗的慢性肾脏病（CKD）动物有蛋白尿、肌酐清除率降低和组织学上有肾脏纤维化的证据。THC+PPC+洛沙坦治疗可显著降低血压，同时增加肾脏中抗氧化铜锌超氧化物歧化酶的信使 RNA 水平，降低蛋白激酶 C-α、肾脏损伤分子-1 和 I 型胶原的水平；与未治疗的 CKD 大鼠相比，白蛋白尿减少，肌酐清除率有增加的趋势。PPC 仅和 THC 治疗的 CKD 大鼠的肾脏组织学纤维化减少。THC+PPC+洛沙坦治疗动物的血浆肾脏损伤分子-1 水平降低。总之，洛沙坦联合 THC 治疗可改善糖尿病 CKD 大鼠的抗氧化水平，减少肾脏纤维化，并降低血压。
