Kidney Toxicity Induced by 13 Weeks Exposure to the Fruiting Body of Paecilomyces sinclairii in Rats

Abstract

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

Keywords: Cystatin C; Kidney damage biomarkers; Kidney injury molecule 1; Kidney toxicity; Paecilomyces sinclairiis.

Fig. 1.. Changes of KIM-1, TIMP-1, osteopontin and cystatin C in kidney of SD rats at 13 weeks of exposure and 2 weeks of postexposure to the diet containing 0 (control group), 5000, 10000 and 50000 ppm Paecilomyces sinclairii. At the end of exposure and recovery period kidney was collected for analysis. The data are expressed as means ± SD for each dose group (n = 10). * p < 0.05 and ** p < 0.01 between control and treatment group.

Fig. 2.. Change of urinary Kim-1, TIMP-1, osteopontin and cystatin C in SD rats at 2, 8 and 13 weeks of exposure and 2 weeks of post-exposure to diet containing 0 (control group), 5000, 10000 and 50000 ppm Paecilomyces sinclairii. During exposure and recovery period, 24-hour urine samples were collected for analysis. The data are expressed as means ± SD for each dose group (n = 5). * p < 0.05 and ** p < 0.01 between control and treatment group.