Galectin 3 inhibition attenuates renal injury progression in cisplatin-induced nephrotoxicity

Area of Science:

• Nephrology
• Biochemistry
• Molecular Biology

Background:

• Chemotherapy-induced nephrotoxicity is a significant cause of acute kidney injury (AKI), often progressing to chronic kidney disease (CKD).
• Limited therapeutic options exist to prevent the progression from AKI to CKD.
• Galectin-3 (Gal-3), a key factor in kidney fibrosis and renal failure, is implicated in renal injury progression.

Purpose of the Study:

• To investigate the role of galectin-3 (Gal-3) in chemotherapy-induced kidney injury.
• To evaluate the therapeutic potential of inhibiting Gal-3 using modified citrus pectin (MCP).
• To elucidate the underlying molecular mechanisms involving protein kinase C alpha (PKC-α).

Main Methods:

• Overexpression of Gal-3 in HEK293 cells to assess its effects on cell viability, cell cycle, and apoptosis.
• Administration of MCP to mice prior to cisplatin-induced kidney injury.
• Analysis of renal function (serum creatinine) and renal tissue damage (histopathology, Masson trichrome staining).
• Western blot analysis to assess apoptosis markers (cleaved caspase-3) and fibrosis markers.

Main Results:

• Ectopic Gal-3 expression reduced cell viability and induced cell cycle arrest and apoptosis in HEK293 cells.
• MCP treatment significantly improved renal function and attenuated kidney fibrosis and apoptosis in cisplatin-injured mice.
• Gal-3 inhibition via MCP was associated with decreased renal fibrosis and apoptosis.
• The protective effect of Gal-3 inhibition was mediated by downregulating PKC-α, which reduced cell apoptosis and collagen I synthesis.

Conclusions:

• Galectin-3 plays a critical role in the progression of kidney injury and fibrosis.
• Modified citrus pectin effectively mitigates cisplatin-induced nephrotoxicity by inhibiting Gal-3.
• Gal-3 and PKC-α represent promising therapeutic targets for treating acute kidney injury (AKI) and chronic kidney disease (CKD).