Gastroprotective effect of rhodanine and 2,4-thiazolidinediones scaffolds in rat stomachs by contribution of anti-apoptotic (BCL-2) and tumor suppressor (P53) proteins.

In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm2, respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm2, 91. 3% and 48.1 ± 0. 8 mm2, 89. 5% and 57. 6 ± 1. 2 mm2, and 89. 1% and 60.3 ± 0. 8 mm2, respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of - 10.7, - 9.0, and - 10.4 (kcal/mol) and - 8.7, - 8.5, and - 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2-8 was variable for both proteins.

In silico and in vivo hepatoprotective activity of the synthesized 5-benzylidene-2-thiohydantoin against diethylnitrosamine-induced liver injury in a rat model.

In the present study, the hepatoprotective effect of 5-benzylidine-2-thiohydantoin (5B2T), a unique derivative of the thiohydantoin group, on liver injury induced by diethylnitrosamine (DEN) in male rats was investigated. The experimental animals were divided into three groups, each with 14 rats. Rats in group I were considered to be controls and received only 10% Tween 80. Rats in group II were injected with 200 mg/kg DEN intraperitoneally. Rats in group III were injected with a single dose of DEN 200 mg/kg intraperitoneally and received the treatment orally (50 mg/kg, 5B2T) for two durations, 3 and 6 weeks. At the end of the experiment, blood was collected for the analysis of liver function and pro-inflammatory cytokine IL-6 and tumor necrosis factor α (TNF-α) levels. Additionally, liver specimens were used for histopathological examination and immunohistochemistry. The single intraperitoneal injection of 200 mg/kg DEN into rats resulted in significant elevation of serum enzyme levels of AST, ALT and ALP, which are indicators of hepatocellular damage, along with elevation in TNF-α and IL-6 in the DEN group. The results of both LFTs and ELISA in the treatment group showed improvements and a decline in the levels of the markers. Histopathological examination showed fibrosis, necrosis and infiltration of inflammatory cells in the DEN group, with lower intensity in the treatment group. The results of immunohistochemical staining revealed strong positive staining of both HSA and Ki-67 antibodies in the DEN group, with much lower intensity in the treatment group. The results of the docking study indicated that 5B2T has a remarkable interaction with TNF-α (PDB ID: 1TNF) and human IL-6 (PDB ID: 1IL6) with binding site energies of - 7.1 and - 6.1 (kcal/mol), respectively. The correct absorption and binding between the drug and the receptor was evaluated through computerized molecular docking by using the AutoDock program. The conclusion of the results from the current study reflected the interesting hepatoprotective abilities of 5B2T against DEN-induced hepatocellular damage and cancer in experimental rats.