Aydin, Ismail Cagri; Ferah Okkay, Irmak; Okkay, Ufuk; Ozkaraca, Mustafa; Yesilyurt, Fatma; Yilmaz, Aysegul; Cicek, Betul; Karatas, Ozhan; Kalkandelen, Hilal Kadioglu; Aydin, Bilge

The present study aimed to unveil the gastroprotective potential of Vaccinium macrocarpon (VM) extract and its mechanism of action against indomethacin (INDO)-induced gastric ulcers in rats. To achieve this goal, rats were pretreated with either omeprazole (20 mg/kg) or VM (100 mg/kg) orally for 14 consecutive days. Gastric tissue samples were collected and various parameters were evaluated to understand the mechanism of VM's action, including the levels of superoxide dismutase, malondialdehyde, glutathione, CAT and transforming growth factor beta (TGF-β), as well as the mRNA expression levels of tumour necrosis factor alpha, interleukin 1 beta, nuclear factor kappa B (NF-κB) and inhibitor kappa B (IκB). Additionally, the immunopositivity of cyclooxygenase (COX)-1, COX-2, PGE2, proliferating cell nuclear antigen (PCNA) and caspase-3 was assessed. The total amount of phenolic compounds present in the VM extract was high (58.08 µg/mL gallic acid equivalent/mg extract). The healing effect of VM was demonstrated by an increase in the expression of PCNA. Furthermore, the level of TGF-β was found to increase upon treatment with VM. Analyses of COX-1, COX-2 and PGE2 expression in gastric tissue confirmed the gastroprotective effect of VM. Notably, the expression of NF-κB was markedly reduced, whereas that of IκB was substantially increased. Overall, the findings of this study demonstrate that VM extract has gastroprotective and curative effects against INDO-induced ulcers through its antioxidant, anti-inflammatory, mucosal regenerative and anti-apoptotic activities. Therefore, VM may serve as a useful adjuvant treatment for nonsteroidal anti-inflammatory drugs–induced gastric ulcer disease.

Corum, Orhan; Uney, Kamil; Coskun, Devran; Durna Corum, Duygu; Cetin, Gul; Elmas, Muammer

Objective: This study aimed to investigate the plasma and milk pharmacokinetics, as well as the withdrawal time (WT) from milk of tolfenamic acid (2 and 4 mg/kg) following intravenous (IV) administration to eight healthy lactating Akkaraman sheep. Methods: The trial was conducted in two periods in accordance with a crossover pharmacokinetic design. The concentrations of tolfenamic acid in the plasma and milk were determined using high-pressure liquid chromatography and evaluated using non-compartmental analysis. The WT of tolfenamic acid in milk was calculated using the WT 1.4 software. Results: Compared to the 2 mg/kg dose, plasma volume of distribution at steady state (from 0.43 to 0.50 L/kg), terminal elimination half-life (from 2.41 to 4.14 h) and dose-normalized area under the plasma concentration–time curve (AUC0−∞, from 9.46 to 30.11 h µg/mL) increased, whereas total body clearance (from 0.21 to 0.13 L/h/kg) decreased at the 4 mg/kg dose. The peak milk concentration (Cmax) and AUC0−∞ values in milk were 0.26 µg/mL and 0.28 h µg/mL, respectively, for 2 mg/kg, and 0.43 µg/mL and 0.55 h µg/mL, respectively, for 4 mg/kg. Although the dose-normalized Cmax of milk decreased depending on the dose, no difference was observed in dose-normalized AUC0−∞. The AUC0−∞ milk/AUC0−∞ plasma ratio was 0.03 for 2 mg/kg and 0.02 for 4 mg/kg. The WT values calculated for milk at dosages of 2 and 4 mg/kg were 3 and 4 h, respectively. Conclusions: A decrease in plasma elimination and an increase in plasma concentration of tolfenamic acid were observed depending on the dose. Tolfenamic acid lowly passed into sheep's milk at 2 and 4 mg/kg doses. This study may provide valuable information for clinicians’ decision-making processes.