Curcumin Prevents Renal Damage of l‐NAME Induced Hypertension in by Reducing MMP‐2 and MMP‐9.

In the present study, we investigated whether curcumin administration would interfere with the main renal features of l‐NAME‐induced hypertension model. For this purpose, we conducted both in vitro and in vivo experiments to evaluate renal indicators of inflammation, oxidative stress, and metalloproteinases (MMPs) expression/activity. Hypertension was induced by l‐NAME (70 mg/kg/day), and Wistar rats from both control and hypertensive groups were treated with curcumin (50 or 100 mg/kg/day; gavage) or vehicle for 14 days. Blood and kidneys were collected to determine serum creatinine levels, histological alterations, oxidative stress, MMPs expression and activity, and ED1 expression. l‐NAME increased blood pressure, but both doses of curcumin treatment reduced these values. l‐NAME treatment increased creatinine levels, glomeruli area, Bowman's space, kidney MMP‐2 activity, as well as MMP‐9 and ED1 expression, and reduced the number of glomeruli. Curcumin treatment prevented the increase in creatinine levels, MMP‐2 activity, and reduced MMP‐2, MMP‐9, ED1, and superoxide levels, as well as increased superoxide dismutase activity and partially prevented glomeruli alterations. Moreover, curcumin directly inhibited MMP‐2 activity in vitro. Thus, our main findings demonstrate that curcumin reduced l‐NAME‐induced hypertension and renal glomerular alterations, inhibited MMP‐2 and MMP‐9 expression/activity, and reduced oxidative stress and inflammatory processes, which may indirectly impact hypertension‐induced renal outcomes. Significance Statement: Curcumin is an intense yellow polyphenol isolated from the plant Curcuma longa Linn. that presents several pharmacological actions. The use of curcumin as a supplement may help to prevent hypertension‐induced kidney damage. This is the first study to show that curcumin prevents renal damage in an l‐NAME hypertension model by reducing MMP‐2, MMP‐9, and ED‐1 macrophage marker levels. Additionally, we first demonstrated a direct inhibition of MMP‐2 by curcumin in vitro. Our results suggest that curcumin may have clinical application as a supplement for hypertension‐induced kidney damage. [ABSTRACT FROM AUTHOR]