title: Chronic ingestion of high dosed Phikud Navakot extraction induces mesangiolysis in rats with alteration of AQP1 and Hsp60 expressions.
abstract: Phikud Navakot (PN) is commonly used in Thai traditional medicine for alleviation of cardiovascular and cerebrovascular symptoms; however little is known about the chronic toxicity effects of the extracts from the herbs in PN. Repeated extraction doses of 10, 100, and 1,000 mg/kg/day were randomly administered to both male and female Sprague Dawley rats for 12 months. Histopathological study revealed that mesangiolysis was predominately found at the highest dose. Aquaporin 1 (AQP1) expression in the mesangiolytic glomeruli was significantly lower than in the intact glomeruli. This may be relevant to an imbalance of vascular function manifested by AQP1 alteration. In the mesangiolytic glomeruli, 60 kDa heat shock protein (Hsp60) was significantly upregulated on the endothelial lining cells of aneurysm and vascular cyst. Hsp60 increase may be related to endothelial cell damage due to its intracellular protective role. Blood urea nitrogen and creatinine levels remained within their normal range indicating well-functioning renal reserve function. In conclusion, high dosed PN may affect the endothelium leading to inability of vascular permeability and consequence to mesangiolysis. Our results suggest that only a high dose of chronic oral administration of PN is relatively toxic in association with mesangiolysis. The NOAEL was determined to be 100 mg/kg/day.
authors: Academic Services Office, National Laboratory Animal Center, Mahidol University, 999 Salaya, Puttamonthon, Nakorn Pathom, Bangkok 73170, Thailand.
authors: Kanchana
authors: 0000-0003-0974-3479
authors: K
authors: Kengkoom
authors: Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand.
authors: Sumate
authors: S
authors: Ampawong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D001774:Blood Chemical Analysis; D018834:Chaperonin 60 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006965:Hyperplasia; D007150:Immunohistochemistry; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D009928:Organ Specificity; D010936:Plant Extracts / Q000008:administration & dosage* / Q000009:adverse effects*; D017207:Rats, Sprague-Dawley
chemical_list: D018834:Chaperonin 60; D010936:Plant Extracts; C000603668:phikud navakot; D051398:Aquaporin 1