Galangin attenuates cadmium-evoked nephrotoxicity: Targeting nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome, nuclear factor erythroid 2-related factor 2, and nuclear factor kappa B signaling.

The kidney is highly vulnerable to cadmium-evoked oxidative injury. Galangin is a natural flavone with reported antioxidant properties. This study investigated the potential modulating activity of galangin against cadmium-induced nephrotoxicity and explored the underlining mechanisms. Western blot analysis, spectrophotometric, ELISA, and histopathological techniques were employed. The results revealed that galangin suppressed tubular injury and improved glomerular function in the cadmium-intoxicated rats as evidenced by downregulation of kidney injury molecule-1, serum creatinine, and blood urea nitrogen. Galangin reduced cadmium-evoked inflammatory response and oxidative stress as indicated by reduced levels of interleukin-1 beta and TNF-α, decreased DNA damage, and improved antioxidant potential of the renal tissues. Mechanistically, galangin suppressed the nucleotide-binding domain-like receptor pyrin domain containing 3 inflammasome and efficiently decreased caspase-1 activity in the cadmium-intoxicated rats. Equally important, it inhibited the cadmium-induced nuclear translocation of nuclear factor kappa B and upregulated nuclear factor erythroid 2-related factor 2 signaling. The results highlight the ability of galangin to attenuate cadmium-evoked nephrotoxicity and support its therapeutic implementation although clinical investigations are warranted.