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. 2022 Dec;27(1):111-118.
doi: 10.1080/13510002.2022.2074128.

Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury

R E Akhigbe  1   2 , D T Oluwole  1 , T E Adegoke  3 , M A Hamed  2   4 , D C Anyogu  5 , A F Ajayi  1
Affiliations

Suppression of glutathione system and upregulation of caspase 3-dependent apoptosis mediate rohypnol-induced gastric injury

R E Akhigbe et al. Redox Rep. 2022 Dec.

Abstract

Objectives: This study investigated the impact of rohypnol on gastric tissue integrity.Methods: Forty male Wistar rats were randomized into control, low dose rohypnol-treated, high dose rohypnol-treated, low dose rohypnol-treated recovery and high dose rohypnol-treated recovery groups.Results: Rohypnol caused significant rise in gastric malondialdehyde (MDA), oxidized glutathione (GSSG), nitric oxide (NO), tumour necrotic factor-α (TNF-α), and interleukin-6 (IL-6) levels. Also, rohypnol caused reductions in gastric reduced glutathione (GSH) (as well as GSH/GSSG), and activities of superoxide dismutase (SOD), catalase, glutathione-S-transferase (GST), glutathione peroxidase (GPx), cyclo-oxygenase (COX-2). Furthermore, rohypnol upregulated caspase 3 activity and induced gastric DNA damage, evident by a rise in 8-hydroxydeoxyguanosine (8-OHdG) and DNA fragmentation index (DFI) in gastric tissue. These alterations were coupled with reduced gastric weight and distorted gastric cytoarchitecture. Cessation of rohypnol caused a significant but not complete reversal of rohypnol-induced gastric damage.Conclusion: This study revealed that rohypnol induced gastric injury by suppressing glutathione content and COX-2 activity, and upregulating caspase 3-dependent apoptosis, which was partly reversed by rohypnol withdrawal.

Keywords: COX; Rohypnol; apoptosis; benzodiazepines; caspase 3; drug abuse‌; glutathione‌; inflammation; oxidative stress; stomach.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Effect of rohypnol on gastric levels of malondialdehyde, MDA (A), reduced glutathione, GSH (B), oxidized glutathione (C), and GSH/GSSG ratio (D). Values are presented as mean ± SD. *P < .05 vs control; #P < .05 vs low-dose; ∼P < .05 vs high-dose, ^P < .05 vs low-dose recovery.
Figure 2.
Figure 2.
Effect of rohypnol on gastric levels of nitric oxide, NO, (A), tumor necrotic factor-α, TNF-α (B), and interleukin-6, IL-6 (IL-6) (C). Values are presented as mean ± SD. *P < .05 vs control; #P < .05 vs low-dose; ∼P < .05 vs high-dose, ^P < .05 vs low-dose recovery.
Figure 3.
Figure 3.
Effect of Rohypnol on gastric levels of cyclo-oxygenase-2 (COX-2). Values are presented as mean ± SD. *P < .05 vs control; #P < .05 vs low-dose; ∼P < .05 vs high-dose.
Figure 4.
Figure 4.
Photomicrographs of the gastric tissue. The gastric tissues of the control (A), low dose Rohypnol-treated (B), and the low dose recovery (D) and high dose recovery (E) groups showed preserved layers; the mucosa (line) lined by simple columnar epithelium lying on a thin layer of the muscularis mucosa (MM, broken black arrow), and the submucosa (SM in red circle) composed of branches of blood vessels (white arrow in blue circle) and lymphatics, the muscularis (M in black circle) and adventitia. The gastric glands (GG in green circle) and gastric pit (GP in yellow circle) appeared unremarkable. However, the gastric tissue of the high dose Rohypnol-treated (C) revealed hyperemic blood vessels (white arrow in blue circle) and moderately atrophied gastric gland (GG in green circle).
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