Dietary copper triggers onset of fulminant hepatitis in the Long-Evans cinnamon rat model

Table 1 Genes analyzed by real-time polymerase chain reaction in liver

Gene symbol	Synonym	Accession number	Primer (forward/reverse)
Vegfa	Vascular endothelial growth factor A	NM031836	CAGTTCGAGGAAAGGGAAAGGCAAATGCTTTCTCCGCTCTG
Hmox1	Heme oxygenase (decycling) 1	NM012580	AGAGGCTAAGACCGCCTTCC AGGCCTCTGGCGAAGAAAC
Cdkn1a	Cyclin-dependent kinase inhibitor 1A	U24174	CTTGCACTCTGGTGTCTCACG ATCGGCGCTTGGAGTGATAG
Timp1	TIMP metallopeptidase inhibitor 1	BC099821	CCTGGTTCCCTGGCATAATC TTGCAAGGGATGGCTGAAC
Srebf1	Sterol regulatory element binding protein-1	AF286470	AGAAGGCCAGTGGGTACCTG TGCGGGCCACAAGAAGTAG

Table 2 Male and female Long-Evans cinnamon rats after copper diet

		Early hCu		Late hCu		rCu		Long-Evans agouti
		Male	Female	Male	Female	Male	Female	Female
Bilirubin	> 0.4 mg/dL1 (d)	55 (67 ± 5)	63 (60 ± 1)	28 (30 ± 1)	28 (32 ± 1)	0.32 (0.3 ± 0)	0.22 (0.2 ± 0)	0.22 (0.2 ± 0)
AST	> 240 U/L1 (d)	74 (75 ± 3)	68 (68 ± 1)	28 (34 ± 3)	30 (33 ± 1)	1152 (117 ± 4)	1032 (103 ± 3)	1142 (114 ± 5)
ALT	> 110 U/L1 (d)	44 (50 ± 2)	54 (54 ± 1)	28 (30 ± 2)	28 (31 ± 1)	692 (69 ± 6)	752 (75 ± 6)	542 (54 ± 1)
Liver Cu	(μg/g)	868 (880 ± 93)	1036 (1058 ± 59)	1494 (1452 ± 161)	1235 (1178 ± 59)	503 (495 ± 75)	309 (326 ± 29)	46 (44 ± 9)
Survival	(day after hCu)	85 (81 ± 4)	81 (75 ± 9)	37 (37 ± 6)	35 (35 ± 2)	NA	NA	NA

NA: Not available; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; hCu: High copper; rCu: Reduced copper.

¹Sera up to sacrifice were analyzed by logrank test using thresholds calculated from Long-Evans agouti rat (mean ± SE) × 2;

²Max values up to sacrifice are given. Data of male and females did not differ (logrank, t test, Kruskal-Wallis, Kaplan-Meier).