Diagnosis of drug-induced renal tubular toxicity using global gene expression profiles

Table 1 In vivo compound treatments used in training and testing

Compound	Class	Conducted by	Dose (mpk)	Necropsy day	Vehicle – Route
Cisplatin	DNA – alkylator	Merck	0.5	3, 8	0.9% (w/v) sodium chloride – IP
			3.5	3, 8
			7	3, 8
Cyclosporin A	Calcineurin inhibitor	Merck	6	3, 9, 15	olive oil – SC
			30	3, 9, 15
			60	3, 9, 15
Gentamycin	Antibiotic	Merck	20	3, 9, 15	0.9% (w/v) sodium chloride – IP
			80	3, 9, 15
			240	3, 9, 12
Sodium Fluoride	Environmental toxin	Merck	35	3, 8, 12	Water – PO
			75	3, 8, 12
Merck X	Antibiotic	Merck	75	3, 8, 14	0.5%saline – IV
			150	3, 8, 14
			225	3, 8
Allopurinol	Xanthine oxidase inhibitor	Charles River	6	3	corn oil – IP
			30	3
			100	3, 7, 14
D-serine	Serine analog	Charles River	750	3, 14	water – IP
Hexachloro 1,3, butadiene	Synthetic toxin	Charles River	7.5	3	corn oil – IP
			40	3, 14
			100	3
Puromycin	Antibiotic	Charles River	5	3	0.9% (w/v) sodium chloride – IP
			20	3, 7, 14
			60	3, 7
Tobramycin	Antibiotic	Charles River	6	3	0.9% (w/v) sodium chloride – IP
			30	14
			60	3, 14

Male Sprague-Dawley rats were treated daily with the listed compounds except D-serine which was given as a single dose once on day 0. Each dose group includes 4 or 5 rats. Animals were terminated at the end of study. Terminal or interim necropsy were performed 24 hours post dosing. Kidney expression profiles were obtained for each necropsy day (when kidney samples were harvested). Appropriate dosing routes were applied: PO – Oral Garvage, IV – intravenous, SC – subcutaneous.

ISSN: 1479-5876