Protein and non-protein sulfhydryls and disulfides in gastric mucosa and liver after gastrotoxic chemicals and sucralfate: Possible new targets of pharmacologic agents

Table 1 Total glutathione (GSH + GSSG) in the mucosa of rat glandular stomach and liver following i.g. administration of gastrotoxic chemicals

	0 min	1 min	3 min	6 min	12 min
Stomach
Ethanol	2.6 ± 0.3	1.7 ± 0.5	1.6 ± 0.3	1.4 ± 0.3a	1.2 ± 0.2b
HCl	2.3 ± 0.7	1.5 ± 0.6	0.9 ± 0.4	0.9 ± 0.3	0.5 ± 0.2a
NaOH	2.6 ± 0.5	2.4 ± 0.4	1.9 ± 0.6	1.9 ± 0.6	1.9 ± 0.5
NaCl	2.9 ± 0.6	2.5 ± 0.5	2.0 ± 0.2	1.8 ± 0.1	1.5 ± 0.3a
Ammonia	3.0 ± 0.7	2.6 ± 0.5	2.3 ± 0.4	2.8 ± 0.4	2.9 ± 0.7
Liver
Ethanol	3.8 ± 0.5	3.9 ± 1.0	4.1 ± 0.6	4.3 ± 0.8	4.2 ± 0.5

The damaging agent, 1 mL of 75% ethanol, 0.6 mol/L HCl, 0.2 mol/L NaOH, 25% NaCl or 1% ammonia-water was given by gavage to fasted S-D rats (n = 4-6), and the animals were killed subsequently at time-points indicated. Data are expressed as mean ± SEM of nmol GSH mg wet tissue.

^aP < 0.05,

^bP < 0.01, vs corresponding control values (0 min).

Table 2 Oxidized glutathione (GSSG) in the mucosa of rat glandular stomach and liver following i.g. administration of gastrotoxic chemicals

	0 min	1 min	3 min	6 min	12 min
Stomach
Ethanol	20.0 ± 3.0	17.0 ± 3.5	26.0 ± 4.0	32.0 ± 5.1	39.0 ± 2.1b
HCl	19.0 ± 6.0	18.0 ± 4.0	18.0 ± 2.8	22.0 ± 4.8	20.0 ± 4.5
NaOH	20.0 ± 2.0	25.0 ± 2.1	26.0 ± 3.7	25.0 ± 4.6	24.0 ± 3.1
NaCl	27.0 ± 1.9	25.0 ± 2.1	35.0 ± 5.7	35.7 ± 6.9	58.0 ± 8.9b
Ammonia	28.1 ± 8.9	34.7 ± 7.1	57.0 ± 9.9	63.0 ± 10.3a	60.0 ± 9.7a
Liver
Ethanol	74.0 ± 13.1	81.4 ± 15.2	64.0 ± 11.3	58.9 ± 10.8	66.6 ± 13.3

The damaging agent, 1 mL of 75% ethanol, 0.6 mol/L HCl, 0.2 mol/L NaOH, 25% NaCl or 1% ammonia-water was given by gavage to fasted S-D rats (n = 4-6), and the animals were killed subsequently at time-points indicated. Data are expressed as mean ± SEM of pmol GSSG in 1 mg wet tissue.

^aP < 0.05,

^bP <0.01, vs corresponding control values (0 min).

Table 3 Protein SH (PSH) in the mucosa of rat glandular stomach and liver following i.g. administration of gastrotoxic chemicals

	0 min	1 min	3 min	6 min	12 min
Stomach
Ethanol	32.9 ± 1.2	29.6 ± 1.9	22.4 ± 1.1b	15.9 ± 1.3d	13.7 ± 1.0b
HCl	34.2 ± 3.0	39.8 ± 2.1	38.7 ± 1.3	35.7 ± 3.3	31.7 ± 4.2
NaOH	26.9 ± 1.0	22.3 ± 2.1	13.0 ± 4.1b	11.8 ± 3.5b	14.0 ± 4.9a
NaCl	26.7 ± 3.6	26.5 ± 2.1	23.1 ± 6.9	13.0 ± 6.7	15.1 ± 2.1a
Ammonia	29.8 ± 2.9	22.6 ± 2.0	26.6 ± 3.9	30.9 ± 2.1	26.3 ± 4.9
Liver
Ethanol	55.4 ± 4.8	51.2 ± 2.4	53.0 ± 1.8	54.3 ± 4.1	50.6 ± 4.5

The damaging agent, 1 mL of 75% ethanol, 0.6 mol/L HCl, 0.2 mol/L NaOH, 25% NaCl or 1% ammonia-water was given by gavage to fasted S-D rats (n = 4-6), and the animals were killed subsequently at time-points indicated. Data are expressed as mean ± SEM of nmol cysteine in 1 mg protein.

^aP < 0.05,

^bP < 0.01,

^dP < 0.001, vs corresponding control values (0 min).

Table 4 Protein-GSH mixed disulfides (PSSG) in rat glandular stomach mucosa and liver following various chemicals given i.g.

	0 min	1 min	3 min	6 min	12 min
Stomach
Ethanol	0.17 ± 0.04	0.28 ± 0.08	0.37 ± 0.03b	0.35 ± 0.02b	0.49 ± 0.04d
HCl	0.20 ± 0.02	0.62 ± 0.11a	0.83 ± 0.15a	0.83 ± 0.16a	0.84 ± 0.09b
NaOH	0.22 ± 0.03	0.31 ± 0.10	0.36 ± 0.09	0.45 ± 0.12	0.43 ± 0.15
NaCl	0.20 ± 0.02	0.19 ± 0.04	0.17 ± 0.04	0.20 ± 0.01	0.22 ± 0.05
Ammonia	0.26 ± 0.03	0.25 ± 0.04	0.27 ± 0.04	0.36 ± 0.11	0.32 ± 0.04
Liver
Ethanol	0.68 ± 0.03	0.86 ± 0.03	0.74 ± 0.03	0.64 ± 0.11	0.81 ± 0.10

The damaging agent, 1 mL of 75% ethanol, 0.6 mol/L HCl, 0.2 mol/L NaOH, 25% NaCl or 1% ammonia-water was given by gavage to fasted S-D rats (n = 4-6), and the animals were killed subsequently at time-points indicated. Data are expressed as mean ± SEM of nmol GSSG in 1 mg protein.

^aP < 0.05,

^bP <0.01,

^dP < 0.001, vs corresponding control values (0 min).

Table 5 Protein disulfides (PSSP) in rat glandular stomach mucosa and liver following various chemicals given i.g.

	0 min	1 min	3 min	6 min	12 min
Stomach
Ethanol	0.55 ± 0.08	0.94 ± 0.06b	1.36 ± 0.20b	1.72 ± 0.05d	1.71 ± 0.13d
HCl	0.54 ± 0.20	0.57 ± 0.04a	0.90 ± 0.30	1.33 ± 0.45	1.69 ± 0.09b
NaOH	0.44 ± 0.07	0.52 ± 0.17	0.55 ± 0.04	0.66 ± 0.14	0.59 ± 0.20
NaCl	0.57 ± 0.02	0.53 ± 0.02	1.00 ± 0.12b	1.01 ± 0.18b	1.35 ± 0.05d
Ammonia	0.39 ± 0.07	0.52 ± 0.17	0.56 ± 0.15	0.78 ± 0.20	0.64 ± 0.15
Liver
Ethanol	0.89 ± 0.25	0.75 ± 0.20	0.95 ± 0.30	0.86 ± 0.17	0.69 ± 0.05

The damaging agent, 1 mL of 75% ethanol, 0.6 mol/L HCl, 0.2 mol/L NaOH, 25% NaCl or 1% ammonia-water was given by gavage to fasted S-D rats (n = 4-6), and the animals were killed subsequently at time-points indicated. Data are expressed as mean ± SEM of nmol half cystine residue in 1 mg protein.

^bP < 0.01,

^dP < 0.001, vs corresponding control values (0 min).

Table 6 Changes in the concentrations of nonprotein and protein sulfhydryls and disulfides in the rat glandular stomach in the early phase of chemically-induced mucosal injury

Agent	Total GSH	GSSG	GSH/GSSG	PSH	PSSG	PSSP	PSH/PSSG	SH/PSSP
Ethanol	DD	II	DD	DD	III	III	DD	DD
HCl	D	I	DD	D	No	II	No	DD
NaOH	DD	No	D	No	I	I	DD	DD
NaCl	No	No	D	D	No	I	DD	D
Ammonia	No	I	D	No	No	No	No	D

Total GSH: GSH + GSSG; GSSG: glutathione disulfide; PSH: protein SH; PSSG: protein-GSH mixed disulfide; PSSP: protein disulfides; I: increase; D: decrease, Ior D: P < 0.05; II or DD: P < 0.01; III or DDD: P < 0.001; No: no significant change in comparison with corresponding controls in the 12 min experiments.