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

Cell Biochem Funct. 2024 Sep;42(7):e4119. doi: 10.1002/cbf.4119.

Abstract

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.

Keywords: kidney damage; l‐NAME induced hypertension; matrix metalloproteinases; oxidative stress.

MeSH terms

  • Animals
  • Curcumin* / pharmacology
  • Hypertension* / chemically induced
  • Hypertension* / drug therapy
  • Hypertension* / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / drug therapy
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • Male
  • Matrix Metalloproteinase 2* / metabolism
  • Matrix Metalloproteinase 9* / metabolism
  • NG-Nitroarginine Methyl Ester* / pharmacology
  • Oxidative Stress / drug effects
  • Rats
  • Rats, Wistar

Substances

  • Curcumin
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Mmp2 protein, rat
  • Mmp9 protein, rat
  • NG-Nitroarginine Methyl Ester