Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress.

AIM

To determine whether oral glutathione (GSH) administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa.

METHODS

Rats were divided into eight groups. One group was fed , another was fed and received oral GSH, and six groups were administrated saline (SA) or GSH orally during fasting. Mucosal height, apoptosis, and cell proliferation in the jejunum were histologically evaluated. iNOS protein expression (by immunohistochemistry), nitrite levels (by high performance liquid chromatography, as a measure of NO production), 8-hydroxydeoxyguanosine formation (by ELISA, indicating ROS levels), glutathione/oxidized glutathione (GSH/GSSG) ratio (by enzymatic colorimetric detection), and γ-glutamyl transpeptidase () mRNA levels in the jejunum (by semi-quantitative RT-PCR) were also estimated.

RESULTS

Oral GSH administration was demonstrated to drastically reduce fasting-induced intestinal atrophy in the jejunum. In particular, jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals [527.2 ± 6.9 for 50 mg/kg GSH, 567.6 ± 5.4 for 500 mg/kg GSH 483.1 ± 4.9 (μm), < 0.01 at 72 h]. This effect was consistent with decreasing changes in GSH-treated animals compared to SA-treated animals for iNOS protein staining [0.337 ± 0.016 for 50 mg/kg GSH, 0.317 ± 0.017 for 500 mg/kg GSH 0.430 ± 0.023 (area of staining part/area of tissue), < 0.01 at 72 h] and NO [2.99 ± 0.29 for 50 mg/kg GSH, 2.88 ± 0.19 for 500 mg/kg GSH 5.34 ± 0.35 (nmol/g tissue), < 0.01 at 72 h] and ROS [3.92 ± 0.46 for 50 mg/kg GSH, 4.58 ± 0.29 for 500 mg/kg GSH 6.42 ± 0.52 (8-OHdG pg/μg DNA), < 0.01, < 0.05 at 72 h, respectively] levels as apoptosis mediators in the jejunum. Furthermore, oral GSH administration attenuated cell proliferation decreases in the fasting jejunum [182.5 ± 1.9 for 500 mg/kg GSH 155.8 ± 3.4 (5-BrdU positive cells/10 crypts), < 0.01 at 72 h]. Notably, both GSH concentration and mRNA expression in the jejunum were also attenuated in rats following oral administration of GSH during fasting as compared with fasting alone [0.45 ± 0.12 0.97 ± 0.06 (nmol/mg tissue), < 0.01; 1.01 ± 0.11 2.79 ± 0.39 ( mRNA/ mRNA), < 0.01 for 500 mg/kg GSH at 48 h, respectively].

CONCLUSION

Oral GSH administration during fasting enhances jejunal regenerative potential to minimize intestinal mucosal atrophy by diminishing fasting-mediated ROS generation and enterocyte apoptosis and enhancing cell proliferation.