Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, and erosions. Carnosic acid (CA) is an important natural antioxidant found in rosemary (Rosmarinus essentials) and exhibits a protective effect by suppressing oxidative stress and inflammation. This study aimed to investigate the impact of CA on IND-induced gastric ulceration. Wistar male rats received CA (100 mg/kg) or esomeprazole (ESP) (20 mg/kg, standard drug) by oral gavage for 14 days, after that gastric ulceration was induced by oral administration of 100 mg/kg IND. CA pretreatment attenuated both gross morphological lesions and histopathological alterations. CA strongly reduced IND-induced oxidative stress, verified by a decrease in MDA (p < 0.001) and TOS levels (p < 0.05). Furthermore, an IND-dependent increase in CAT (p < 0.001) and GPx (p < 0.01) activities, as well as a reduction in GSH levels (p < 0.01), were ameliorated by CA pretreatment. CA also attenuated inflammatory damage by suppressing IL-1β (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) production and increasing Nrf2/HO-1 (p < 0.05) expressions. In conclusion, CA shows a gastroprotective effect by reducing oxidative stress and attenuating inflammation.
Gastric ulcer is one of the most common diseases of the gastrointestinal system and some of its complications are the main causes of morbidity and mortality. Bromelain (BRM), a sulfhydryl proteolytic enzyme, has multiple activities in many areas of medicine as an antioxidant and anti-inflammatory agent. In this study, it was aimed to investigate the anti-inflammatory and oxidative stress-mediated therapeutic effect of BRM in a gastric ulcer model induced by indomethacin (IND) which is a non-steroidal anti-inflammatory drug (NSAID) with gastric ulcer-forming effects. Gastric mucosal paraoxonase (PON), arylesterase (ARE), catalase (CAT), myeloperoxidase (MPO) and glutathione peroxidase (GPx) activity and total glutathione (GSH) levels were analyzed. Interleukin-33 (IL-33), the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) levels were determined by immunohistochemically. Although IND-induced histopathological changes occurred, BRM pretreatment prevented these effects. As a result of the study, it was determined that BRM had an anti-ulcerative effect at a dose of 50 mg/kg. BRM given at this dose significantly decreased gastric tissue MPO activity, and increased CAT, PON, ARE, GPx activity and GSH level. The increased IL-33 and decreased Nrf-2 and HO-1 levels were obtained in IND group and these changes were reversed by BRM. As a result, it was concluded that BRM may have protective effects in IND-induced gastric model by reducing inflammation and regulating oxidant/antioxidant balance.
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