Red yeast rice supplement containing silica nanoparticles induces renal injury in rats with unilateral nephrectomy

TL;DR

Red yeast rice supplements with silica nanoparticles may cause kidney damage in rats with one kidney.

Contribution

The study identifies silica nanoparticle accumulation as a potential cause of kidney injury in rats with unilateral nephrectomy.

Findings

Silica nanoparticles from CP tablets accumulated in the proximal tubules of uninephrectomized rats.

Unilateral nephrectomy increased susceptibility to CP-induced renal injury.

PA alone at CP tablet doses did not cause significant kidney damage.

Abstract

Acute kidney injury (AKI) caused by red yeast rice Cholestehelp® (CP) tablets has become a public health issue in Japan. Puberulic acid (PA) contaminated in CP tablets may cause AKI; however, we detected silica nanoparticles in a CP patient. CP-related kidney injury was examined in rats that underwent left nephrectomy to increase silica nanoparticle loading.

Six male Sprague–Dawley rats were administered CP and underwent left nephrectomy on day 4. Blood and urine samples were collected on day 11. Renal tissues were observed by electron microscopy and low-vacuum scanning electron microscopy-energy dispersive X-ray spectroscopy (LVSEM-EDS). The amount of PA in CP was measured, and PA was administered to normal rats and unilaterally nephrectomized rats.

Normal rats receiving CP (2KCP) had increased urine volume and lower urine specific gravity than controls, but no significant changes were observed in urinary protein, renal function, electrolytes, or blood gasses. Unilaterally nephrectomized rats receiving CP (1KCP) had increased water intake and urine volume, decreased urine specific gravity, and increased low-molecular-weight proteinuria. The glomeruli of 1KCP rats showed expanded subendothelial space and increased endocytic vesicles were observed in the proximal tubules relative to 2KCP rats. The accumulation of nanoparticles in the endosomes of the proximal tubules, and LVSEM-EDS detected silicon in renal tissue. Administration of PA at the doses in CP tablet did not result in significant renal injury.

Uninephrectomized rats administered CP tablets showed accumulation of silicon-containing nanoparticles in the proximal tubules and renal injury.

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