Toxicol Res.  2012 Sep;28(3):179-185.

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

Affiliations
  • 1Agro-Material Safety Evaluating Division, National Academy of Agricultural Science, Rural Development Administration, Suwon 441-707, Korea.
  • 2Department of Bio Applied Toxicology, Hoseo Toxicology Research Center, Hoseo University, Asan 336-795, Korea. Jeongsh@hoseo.edu
  • 3Environmental Science and Ecological Engineering, Korea University, Seoul 136-701, Korea.

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 (beta2m), glutathione S-transferase alpha (GST-alpha), 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.

Keyword

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

MeSH Terms

Animals
Biomarkers
Blood Urea Nitrogen
Calcium-Binding Protein, Vitamin D-Dependent
Clusterin
Creatinine
Cystatin C
Female
Filtration
Fruit
Functional Food
Glutathione Transferase
Humans
Hypertrophy
Isoenzymes
Kidney
Lipocalins
Male
Matrix Metalloproteinase 1
Neutrophils
Osteopontin
Paecilomyces
Rats
Tissue Inhibitor of Metalloproteinase-1
Vascular Endothelial Growth Factor A
Calcium-Binding Protein, Vitamin D-Dependent
Clusterin
Creatinine
Cystatin C
Glutathione Transferase
Isoenzymes
Lipocalins
Matrix Metalloproteinase 1
Osteopontin
Tissue Inhibitor of Metalloproteinase-1
Vascular Endothelial Growth Factor A
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