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Protective effect of GYY4137, a water‑soluble hydrogen sulfide‑releasing molecule, on intestinal ischemia‑reperfusion
Ning Cui1, Hesheng Luo1, Yu Zhao1
1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Abstract:
The present study aimed to clarify the protective effects of p‑methoxyphenyl morpholino‑phosphinodithioic acid (GYY4137), a water‑soluble hydrogen sulfide‑releasing molecule, on a rat model of intestinal ischemia‑reperfusion (IIR). A total of 40 healthy male Sprague Dawley (SD) rats were randomly divided into four groups (n=10/group): Group A, a sham‑surgery group; Group B, the IIR group; group C, rats with IIR that were administered an abdominal injection of low‑dose GYY4137 (40 mg/kg); and group D, rats with IIR that were administered high‑dose GYY4137 (80 mg/kg). Intestinal histomorphology was observed using hematoxylin and eosin staining, and the concentrations of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured. Apoptotic index (AI) was determined by terminal deoxynucleotidyl‑transferase‑mediated dUTP nick end labeling. Reverse transcription‑quantitative PCR analysis was performed to assess the expression levels of intestinal caspase‑3, Bax and Bcl‑2. Notably, disordered arrangement of intestinal villi and mucosal necrosis were detected in group B, which was substantially improved by GYY4137 treatment (groups C and D). MDA content (nmol/mg) was 2.83±0.36, 9.23±0.78, 4.97±0.45 and 3.51±1.05 nmol/mg in groups A, B, C and D, respectively. In addition, SOD concentration (U/mg) was 135.37±3.34, 76.45±1.39, 95.13±1.64 and 115.13±2.54 in groups A, B, C and D, respectively. Furthermore, AI in group B (21.73±1.17%) was markedly higher than that in group A (4.53±0.28%) and in the GYY4137 intervention groups (9.53±0.96 and 6.53±0.76% in groups C and D, respectively). Compared with in group A, the mRNA expression levels of Bax and caspase‑3 were markedly higher in group B (P<0.05), whereas the expression of Bcl‑2 was significantly lower (P<0.05). Furthermore, compared with in group B, Bcl‑2 expression was higher, and Bax and caspase‑3 expression was lower in groups C and D (P<0.05). In conclusion, GYY4137 may alleviate IIR‑induced damage in SD rats.
Insights
p‑methoxyphenyl morpholino‑phosphinodithioic acid (GYY4137), a hydrogen sulfide donor, protected rats from intestinal ischemia‑reperfusion (IIR) injury. GYY4137 treatment reduced tissue damage, apoptosis, and inflammatory markers, improving intestinal health.
Area of Science:
- Gastroenterology
- Physiology
- Pharmacology
Background:
- Intestinal ischemia-reperfusion (IIR) injury is a critical condition with significant morbidity.
- Hydrogen sulfide (H2S) is recognized for its protective roles in various injury models.
- GYY4137 is a novel, water-soluble H2S-releasing molecule with potential therapeutic applications.
Purpose of the Study:
- To investigate the protective effects of GYY4137 against IIR-induced damage in a rat model.
- To evaluate the impact of different GYY4137 dosages on intestinal histomorphology and biochemical markers.
- To assess the modulation of apoptosis and gene expression related to cell death pathways by GYY4137.
Main Methods:
- Establishment of an IIR model in Sprague Dawley rats, divided into sham, IIR, and two GYY4137-treated groups (low and high dose).
- Histopathological examination using hematoxylin and eosin staining.
- Measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels.
- Assessment of apoptotic index (AI) via TUNEL assay.
- Quantitative PCR analysis for Bax, Bcl-2, and caspase-3 mRNA expression.
Main Results:
- GYY4137 treatment significantly improved intestinal villi structure and reduced mucosal necrosis compared to the IIR group.
- MDA levels were decreased, and SOD activity was increased in GYY4137-treated rats.
- GYY4137 administration markedly reduced the apoptotic index and modulated the expression of apoptosis-related genes (Bax, caspase-3, Bcl-2).
Conclusions:
- GYY4137 demonstrates significant protective effects against IIR-induced intestinal injury in rats.
- The therapeutic benefits are associated with reduced oxidative stress, decreased apoptosis, and favorable regulation of apoptotic gene expression.
- GYY4137 holds promise as a potential therapeutic agent for managing intestinal ischemia-reperfusion injury.
