Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats

Erol, Huseyin Serkan/0000-0002-9121-536X; KOCPINAR, ENVER FEHIM/0000-0002-6031-4664; Budak, Harun/0000-0002-7371-8959; /0000-0001-6208-165XWOS:000551592600001PubMed: 30426792Ethnopharmacological studies demonstrated that thymol (Thym) and oleuropein (Ole) have therapeutic potential for gastric ulcers. The molecular mechanism underlying the gastroprotective effects of these compounds have not been elucidated yet especially for their individual and combination use at high dose. Therefore, this study was conducted to explore their gastroprotective mechanisms on indomethacin (Indo)-induced gastric ulcer model. Ole (50,100, 250, and 500 mg/kg) and Thym (50,100, 200, and 500 mg/kg) were orally administered to the rats 10 min before the induction of ulcer with Indo. The combination of 500 mg/kg doses of Ole and Thym were applied. The gastric mucosa was evaluated histopathologically. Moreover, TAC/TOS, tumor necrosis factor-alpha (TNF-alpha), prostaglandin E-2(PGE(2)), endothelial nitric oxide synthase (eNOS), and caspase-3 levels were assessed by ELISA and the caspase-3 and TNF-alpha expressions were quantified by qRT-PCR. Indo-induced histopathological changes while Ole and Thym pretreatment prevented these effects. Unlike the 500 mg/kg dose of Ole treatment, the 500 mg/kg dose of Thym administration enhanced these damages. The decreased TAC, PGE(2)levels and increased TOS, eNOS, TNF-alpha, caspase-3 levels were obtained in Indo group. However, these changes were reversed by Ole and Thym groups except the 500 mg/kg dose of Thym and the combination treatment groups. Similar trends were observed in the caspase-3 and TNF-alpha expression levels. These results demonstrated that enhanced inflammation, oxidant/antioxidant imbalance, and apoptotic activities were occurred in Indo, 500 mg/kg dose of Thym and the combination treatment groups while not in the other groups. The findings demonstrated the gastroprotective ability of Ole and low doses of Thym in gastric ulcer models

Toxicological evaluation of submerged liquid culture from Phanerochaete chrysosporium mycelium on human blood cells: cytotoxicity, genotoxicity and oxidative damage

Mushrooms produce a variety of bioactive antioxidant secondary metabolites including ectins, polysaccharides, pigments, phenolic compounds, sterols and terpenes. Extracellular and intracellular compounds produced by submerged liquid fermentation are important industrially and economically. Phanerochaete chrysosporium (PC) is the model white-rot fungus that easy cultivation on lignocellulose-containing substrates. PC can be used as a bioprotein source. Aims of this study were to determine the in vitro antioxidant, cytotoxic and genotoxic effects of hot water extract obtained from PC on human peripheral blood monunuclear cells (hPBMCs). Cytotoxicity was determined by lactate dehydrogenase (LDH) leakeage assay and neutral red (NR). Total antioxidant capacity (TAC) and total oxidant status (TOS) were detected to determine the oxidative damage. Genotoxicity was characterized by micronuclei and chromosome aberrations assays for specify DNA damage. PC (5-75 µg/ml) significantly increased antioxidant capacity and these doses did not cause any significant alterations to cytotoxicity on hPBMCs. The elavated doses of PC (5-250 µg/ml) did not cause increase in genotoxic. Whereas, 250 and 500 µg/ml doses of PC statistically increased TOS levels, NR uptake, LDH release, CA/cell frequency and MN formation however decreased TAC levels. This study is the first time on cytotoxicity, genotoxicity and oxidative damage of PC on hPBMCs. In conclusion, the consumption of PC can be safe for humans, but it has also exposure period and dose-dependent effects on inducing oxidative damage and toxicity on hPBMCs

Hepatoprotective Role of Thymol in Drug-Induced Gastric Ulcer Model

Introduction and aim. Indo is widely one of the non-steroidal anti-inflammatory drugs and one of the common toxic effects of this drug is hepatic failure. Thymol is a monoterpene phenol with many different pharmacological activities. However, up to now its hepatoprotective effects on Indo-induced gastric ulcer model in rats have not been explored yet.Material and methods. Thirty five Sprague-Dawley rats were divided into seven groups: control, ulcer control (30 mg/kg Indo), Indo + reference standard (50 mg/ kg Rantidine), Indo + Thymol (75, 100, 250 and 500 mg/kg) groups. 10 minutes after the induction of ulcer with Indo; Thymol was orally administered to the rats. Liver function enzymes (AST, ALT and LDH) were measured from serum samples. TOS/TAC, TNF-α and PGE2 levels, eNOS and Caspase-3 activity were assessed from tissue homogenate samples. In addition, histopathologic analysis on liver sections was performed.Results. Indo significantly increased the levels of hepatic enzymes, TNF-α and eNOS, and caspase-3 activation, while decreased PGE2 levels. Furthermore, it induced oxidative stress as evidenced by elevated TOS and decreased TAC levels. However, Thymol treatment induced a significant improvement in these parameters, especially in 250 mg/ kg dose. On the other hand, treatment with Thymol 500 mg/kg dramatically affected the parameters much worse than the Indo treated group.Conclusion. The findings of the current study demonstrated that Thymol administration significantly ameliorated liver injury due to Indo toxicity. This effect of Thymol (250 mg/kg) may be mediated by its anti-oxidative or anti-inflammatory effect, and up-regulation the synthesis of PGE2

Effect of oleuropein against chemotherapy drug-induced histological changes, oxidative stress, and DNA damages in rat kidney injury

Cisplatin-based chemotherapy is responsible for a large number of renal failures, and it is still associated with high rates of mortality today. Oleuropein (OLE) presents a plethora of pharmacological beneficial properties. In this study we investigated whether OLE could provide sufficient protection against cisplatin-induced nephrotoxicity. With this aim, Sprague-Dawley rats were divided into eight groups: control; 7 mg/kg/d cisplatin, 50 mg/kg, 100 mg/kg, and 200 mg/kg OLE; and treatment with OLE for 3 days starting at 24 hours following cisplatin injection. After exposure to the chemotherapy agent and OLE, oxidative DNA damage was quantitated in the renal tissue of experimental animals by measuring the amount of 8-hydroxy-2′-deoxyguanosine (8-OHdG) adducts. Malondialdehyde (MDA) level, total oxidative stress (TOS), and total antioxidant status (TAS) were assessed to determine the oxidative injury in kidney cells. The histology of the kidney was examined using four different staining methods: hematoxylin-eosin (H&E), periodic acid Schiff (PAS), Masson trichrome, and amyloid. In addition, the blood urea nitrogen (BUN), uric acid (UA), and creatinine (CRE) levels were established. Our experimental data showed that tissue 8-OHdG levels were significantly higher in the cisplatin group when compared to the control group. The glomerular cells were sensitive to cisplatin as tubular cells. In addition, treatment with cisplatin elevated the levels of BUN, UA, CRE, and TOS, but lowered the level of TAS compared to the control group. The OLE therapy modulated oxidative stress in order to restore normal kidney function and reduced the formation of 8-OHdG induced by cisplatin. Furthermore, the OLE treatment significantly reduced pathological findings in renal tissue. We demonstrate for the first time that OLE presents significant cytoprotective properties against cisplatin-induced genotoxicity by restoring the antioxidant system of the renal tissue. According to our findings, OLE is a promising novel natural source for the prevention of serious kidney damage in current chemotherapies

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-alpha levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries