Table 1 Summary and comparison of APAP-induced effects in age-matched fasted and nonfasted male CD-1 mice and Z-VAD.fmk (10 mg/kg) pretreated fed mice (APAP 530 mg/kg; 5h and 24 h).^a

5 h after dose

Irreversible binding, nmol/mg

—

1.87 (0.45)

—

1.95 (0.44)

—

1.82 (0.64)

Hepatic ATP, nmol/mg

35.5 (4.0)

5.2 (2.1)^c

17.1 (5.3)

2.3 (1.0)^c

37.4 (6.1)

3.1

(1.4)^c

Hepatic GSH, nmol/mg

70.6 (10.6)

9.6 (5.1)^c

42.6 (5.9)

3.6 (1.8)^c

63.2 (12.5)

15.3

(7.8)^c

Serum total HMGB1, ng/mL

7.4 (5.2)

210.2 (55.1)^c

20.1 (6.3)

295.8 (20.3)^{d, e}

2.5 (5.4)

301.9

(24.0)^{d, e}

Hypoacetylated HMGB1, fold increment

N/D

17.4 (2.3)^d

N/D

24.1 (5.1)^{d, e}

N/D

27.3

(3.4)^{d, e}

Hyperacetylated HMGB1, fold increment

N/D

1.4 (0.2)^b

N/D

1.6 (0.4)^b

N/D

2.1

(0.4)^b

Serum K18 fragments, pmol/mL

126.2 (25.1)

801.4 (198.1)^b

176.7 (62.3)

232.4 (201.6)^e

107.8 (40.3)

164.9

(78.4)^e

Serum full-length K18, pmol/mL

6.5 (2.4)

15,246.1 (804.3)^d

8.9 (4.5)

19,057.5 (1024.7)^{d, f}

7.1 (2.4)

23,614.0

(1237.2)^{d, f}

Serum ALT activity, U/L

78.2 (65.4)

2,146.4 (1012.3)^b

49.8 (27.5)

2,048.6 (461.7)^c

35.8 (10.5)

3,607.0

(782.1)^{c, e}

Serum TNF-α, pg/mL

51.4 (12.4)

62.1 (13.5)

57.1 (13.0)

101.2 (40.1)

68.1 (22.1)

60.4

(7.8)

Serum IL-6, pg/mL

25.4 (6.7)

54.3 (10.2)^b

23.1 (4.0)

35.4 (10.5)^e

34.0 (9.8)

50.4

(18.4)

24 h after dose

Irreversible binding, nmol/mg

—

—

—

—

—

Hepatic ATP, nmol/mg

33.1 (2.1)

27.4 (6.6)

16.4 (3.7)

5.1 (2.0)^{c, f}

37.4 (7.1)

31.5

(3.9)

Hepatic GSH, nmol/mg

65.4 (10.7)

58.3 (5.9)

39.7 (6.3)

22.5 (8.5)^{b, e}

73.8 (15.9)

47.9

(10.1)^{b, e}

Serum total HMGB1, ng/mL

10.2 (7.4)

17.5 (5.5)

15.4 (3.5)

353.1 (28.6)^{d, g}

4.7 (3.1)

429.5

(42.0)^{d, g}

Hypoacetylated HMGB1, fold increment

N/D

N/D

N/D

33.6 (5.8)^d

N/D

35.6

(4.7)^d

Hyperacetylated HMGB1, fold increment

N/D

1.7 (0.3)

N/D

14.9 (4.2)^{c, f}

N/D

17.2

(3.2)^{c, f}

Serum K18 fragments, pmol/mL

102.6 (35.1)

914.0 (103.2)^b

150.1 (21.5)

160.4 (42.9)^e

183.4 (71.0)

162.2

(39.2)^e

Serum full-length K18, pmol/mL

5.4 (1.2)

17,610.0 (1599.5)^d

13.6 (6.9)

26,721.6 (3853.0)^{d, f}

10.3 (5.8)

30,016.6

(2128.6)^{d, f}

Serum ALT activity, U/L

27.5 (5.7)

2,654.5 (334.5)^c

63.2 (22.5)

3,603.8 (508.8)^{c, e}

50.2 (11.2)

4,891.6

(701.2)^{c, f}

Serum TNF-α, pg/mL

45.8 (6.4)

95.0^b (14.1)

63.1 (19.7)

227.8 (53.6) ^{c, f}

54.7 (16.1)

262.2

(39.7) ^{d, f}

Serum IL-6, pg/mL

30.1 (2.0)

203.0 (39.6) ^c

27.5 (12.6)

96.4 (35.2)^{b, f}

26.6 (3.3)

100.8

(28.1)^{b, f}