Abstract
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.
Highlights
The pathogenesis of chronic kidney disease (CKD) involves a complex interaction of inflammation, oxidative stress, and fibrosis thatAbbreviations: BP, blood pressure; BUN, blood urea nitrogen; CKD, chronic kidney disease; CrCl, creatinine clearance; CRP, C-reactive protein; PPC, polyenylphosphatidylcholine; ROS, reactive oxygen species; THC, tetrahydrocurcumin.lead to progressive glomerular and tubulointerstitial scarring.[1,2] Oxidative stress promotes inflammation via toxic effects of reactive oxygen species (ROS) and by activation of redox-sensitive proinflammatory signaling pathways
We report that THC with PPC had positive renal effects, which correlated with decreased systemic hypertension and less cardiac hypertrophy
To the best of our knowledge, this is the first study of dietary tetrahydrocurcumin in 5/6 nephrectomy rats
Summary
The pathogenesis of chronic kidney disease (CKD) involves a complex interaction of inflammation, oxidative stress, and fibrosis that. Inflammation and oxidative stress perpetuate atherosclerosis and vascular calcification, directly contributing to the elevated cardiovascular morbidity and mortality rates in CKD patients.[2,3] THC prevented ferric nitrilotriacetate and chloroquine-induced oxidative kidney injury via inhibition of lipid peroxidation and upregulation of antioxidant catalytic activity.[12,13] In rats with streptozotocin-induced diabetes mellitus, THC has been shown to decrease tissue oxidative stress, decrease albuminuria and serum creatinine, and improve plasma insulin levels.[14,15,16] Curcumin but not THC has previously been investigated in 5/6 nephrectomized CKD rats 17-19 and we chose to study THC in this nephron mass reduction model to determine effects on proteinuria, fibrosis, and inflammation. We report that THC with PPC had positive renal effects, which correlated with decreased systemic hypertension and less cardiac hypertrophy
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