Curcumin prevents cisplatin-induced decrease in the tight and adherens junctions: relation to oxidative stress.

Area of Science:

• Nephrology
• Pharmacology
• Biochemistry

Background:

• Cisplatin, an antineoplastic agent, causes nephrotoxicity via oxidative stress, apoptosis, and fibrosis.
• Renal tight junction (TJ) and adherens junction (AJ) proteins are compromised in cisplatin-induced kidney injury.
• The protective effects of curcumin on cisplatin-induced alterations in TJ and AJ proteins remain unevaluated.

Purpose of the Study:

• To investigate curcumin's potential to prevent fibrosis and decreased expression of TJ/AJ proteins (occludin, claudin-2, E-cadherin) in cisplatin-induced nephrotoxicity.
• To assess curcumin's antioxidant capacity against various reactive oxygen species.
• To determine if curcumin mitigates cisplatin-induced oxidative stress and related molecular changes in the kidney.

Main Methods:

• Rats were administered cisplatin followed by curcumin (200 mg kg(-1)) in three doses.
• Renal function, oxidative stress markers, apoptosis, fibrosis, and TJ/AJ protein expression were evaluated 72 hours post-cisplatin.
• In vitro antioxidant assays assessed curcumin's radical scavenging activity.
• NADPH oxidase activity and its subunits were analyzed in isolated glomeruli and proximal tubules.

Main Results:

• Curcumin demonstrated concentration-dependent scavenging of superoxide anion, hydroxyl radical, and other reactive oxygen species.
• Cisplatin induced significant renal damage, characterized by elevated creatinine, kidney injury markers, apoptosis, fibrosis, and increased oxidative stress.
• Curcumin treatment effectively prevented cisplatin-induced renal damage, fibrosis, apoptosis, and the decrease in occludin, claudin-2, β-catenin, and E-cadherin.
• Curcumin's protective effect was linked to the inhibition of glomerular and proximal tubular superoxide anion production mediated by NADPH oxidase.

Conclusions:

• Curcumin exhibits potent antioxidant properties and effectively protects against cisplatin-induced nephrotoxicity.
• Curcumin preserves renal structure and function by preventing fibrosis and maintaining the integrity of tight junction and adherens junction proteins.
• The renoprotective mechanism of curcumin involves the suppression of NADPH oxidase-dependent oxidative stress in the kidney.