Mesut Halici

Beneficial effects of vegetable oils (corn, olive and sunflower oils) and α-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin in rats

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin are widely used in the treatment of inflammation, fever and pain. However, NSAIDs cause gastric damage as a major adverse reaction. In this study, the effects of vegetable oils (corn, olive and sunflower oils) and alpha-tocopherol on anti-inflammatory and gastrointestinal profiles of indomethacin were evaluated in rats. Results showed that indomethacin given with sunflower, corn and olive oils reduced paw edema induced by carrageenan by 79.5%, 74.0% and 60.5%, whereas individual indomethacin and diclofenac reduced paw edema by 56.2% and 50.7%, respectively. Furthermore, it has been found that the vegetable oils possess significant anti-inflammatory effect against paw edema when given alone. These results showed that the vegetable oils have beneficial effects on reduction paw edema induced by carrageenan. Besides, the administration of indomethacin together with the vegetable oils and alpha-tocopherol did not cause a statistically significant gastric damage in rats (P>0.05). However, indomethacin caused statistically significant gastric lesions as compared with untreated rats (P<0.05). Moreover, it was also found that the effects of the vegetable oils and alpha-tocopherol improved the levels of antioxidant defense systems in rat stomach tissues against oxidative damage. These results suggest that indomethacin as well as other NSAIDs do not have any adverse effect on the gastrointestinal tract when they are used together with vegetable oils and vitamin E or as the preparations of the oils.

Alpha-lipoic acid as a potential target for the treatment of lung injury caused by cecal ligation and puncture-induced sepsis model in rats.

One of the common lethal complications of septic shock, a major cause of morbidity and mortality in patients with severe trauma and so on, is acute lung injury. &agr;-Lipoic acid (ALA), with antioxidant properties, is a popular agent. Thus, we investigated the potential protective effects of ALA (200 mg/kg) on sepsis-induced acute lung injury. Rats were exposed to cecal ligation and puncture (CLP) to induce sepsis. Rat groups were designed as (a) sham operated, (b) sham operated + ALA treated, (c) CLP applied, (d) CLP + ALA treated. Sixteen hours after CLP induction, serum samples and lung tissues were obtained for biochemical and histopathological examination. &agr;-Lipoic acid decreased the serum levels of inflammatory cytokines such as TNF-&agr; and IL-6, which increased after CLP. Increased activity of nuclear factor &kgr;B in septic lung tissues was decreased by ALA. &agr;-Lipoic acid improved the decreased antioxidant activity and alleviated the increased oxidant activity, which occurred after CLP application. We can suggest that ALA showed beneficial effects by decreasing nuclear factor &kgr;B activation in lung tissues, resulting in decreased serum levels of TNF-&agr; and IL-6, and also increasing the antioxidant capacity of the lungs.

Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.

An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities.

Alpha-lipoic acid protects against indomethacin-induced gastric oxidative toxicity by modulating antioxidant system.

Gastroprotective effects of α-lipoic acid (ALA) against oxidative gastric damage induced by indomethacin (IND) have been investigated. All doses (50, 75, 100, 150, 200, and 300 mg/kg body weight) of ALA reduced the ulcer index with 88.2% to 96.1% inhibition ratio. In biochemical analyses of stomach tissues, ALA administration decreased the level of lipid peroxidation (LPO) and activities of myeloperoxidase (MPO) and catalase (CAT) in gastric tissues, which were increased after IND application. ALA also increased the level of glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione S-transferase (GST) that were decreased in gastric damaged stomach tissues. In conclusion, the gastroprotective effect of ALA could be attributed to its ameliorating effect on the antioxidant defense systems.

Effects of α‐lipoic acid, vitamins E and C upon the heat stress in Japanese quails

Antioxidant vitamins are commonly used as colorant, preventive, sweetener, nutritive and antioxidant materials in food industry. Thus, many studies have been conducted in recent years. We have performed the present study to understand the effects of α-lipoic acid (ALA), vitamin C and E, added into rations of Japanese quails, on chronic heat stress. This study was carried out in five groups as: control, stress, ALA, vitamin E and vitamin C groups. Heat stress is applied to all groups except the control group. Superficial pectoral muscles tissues were used for biochemical determinations. During the research, it is found that heat stress exerted undesired effects such as increasing lipid peroxidation (LPO) level indicating oxidative stress in Japanese quails. In addition, superoxide dismutase (SOD) and catalase (CAT) enzyme activities and glutathione (GSH) amounts were studied to understand the behaviour of defence mechanism. While stress increased LPO ratio, it was determined that all antioxidant added into the ration decreases LPO significantly (p < 0.05). In addition, it was determined that all of antioxidants added into ration effectively restored SOD activity and LPO ratio which heat stress affected negatively. Interestingly, vitamin C did not adjust GSH ratio in contrast to vitamin E and ALA, where vitamin E and C did not perform any positive effect on heat stress decreased CAT activity. Finally, it can be thought that antioxidant vitamins relatively ameliorated these undesired affects caused by stress factors given.

The effects of methanol extract of Lobaria pulmonaria, a lichen species, on indometacin-induced gastric mucosal damage, oxidative stress and neutrophil infiltration

Lobaria pulmonaria, a lichen species, has been used in traditional medicine for the treatment of various diseases. This study was designed to determine the gastroprotective effect of the methanol extract of L. pulmonaria in an indometacin‐induced ulcer model in rats. The results showed that gastric lesions were significantly reduced in a dose‐dependent manner. Furthermore, the administration of indometacin caused a significant decrease in the levels of superoxide, glutathione peroxidase and reduced glutathione and an increase in the lipid peroxidation level. Administration of the lichen extract, however, produced an increase in the levels of these enzymes and a decrease in lipid peroxidation levels, although catalase and myeloperoxidase levels were unaffected. The present results suggested that Lobaria pulmonaria has a gastroprotective effect, probably due to reducing oxidative stress and neutrophil infiltration. Copyright

Melatonin Attenuates Contrast-Induced Nephropathy in Diabetic Rats: The Role of Interleukin-33 and Oxidative Stress

Background. Inflammation and oxidative stress (OxS) contribute to the pathogenesis of diabetic kidney disease (DKD) and contrast-induced nephropathy (CIN). Patients with DKD were found to be more prone to CIN. Interleukin-33 (IL-33) is a proinflammatory cytokine, but its role in DKD and CIN is unknown. Methods. Thirty male Sprague-Dawley rats were enrolled. The first group was comprised of healthy rats (HRs), whereas the other four groups were made up of diabetic rats (DRs), diabetic rats with contrast-induced nephropathy (CIN + DRs), melatonin-treated diabetic rats (MTDRs), and melatonin-treated CIN + DRs (MTCIN + DRs). All groups except the HRs received 50 mg/kg/day streptozotocin (STZ). CIN + DRs were constituted by administrating 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. MTDRs and MTCIN + DRs were given 20 mg/kg/day of intraperitoneal injection of melatonin (MT) from the 28th day for the constitutive seven days. Results. We observed increased IL-33 in the kidney tissue following induction of CIN in DRs. To determine whether MT is effective in preventing CIN, we administered MT in CIN + DRs and demonstrated that kidney tissue levels of OxS markers, inflammatory cytokines, and IL-33 were significantly diminished in MTCIN + DRs compared with other groups without MT treatment (p < 0.05). Conclusion. Inhibition of IL-33 with MT provides therapeutic potential in DKD with CIN.

Diffractaic acid, a novel proapoptotic agent, induces with olive oil both apoptosis and antioxidative systems in Ti-implanted rabbits☆

Usnea longissima Ach., a lichen species, is a traditional herbal medicine with anti-detrimental effects. We evaluated the in vivo effects of a major constituent of U. longissima, diffractaic acid, and the main fatty component of the Mediterranean diet, olive oil, against apoptosis, including various caspase activations and oxidative injury in surrounding tissues after titanium implantation in rabbit femurs. Furthermore, we evaluated the underlying molecular mechanisms. In this study, this lichen metabolite and olive oil activated caspase-dependent cell death with apoptotic morphology, which is distinctly different from necrosis. Both orally and locally administered olive oil and diffractaic acid exerted pro-apoptotic induction in tissues surrounding the implants in titanium-implanted rabbits through the activation of initiator caspases (Cas-2, -8 and -9) and executioner caspase (Cas-3). In addition, they displayed strong myeloperoxidase and inducible nitric oxide synthase activities, providing an alleviating effect. Furthermore, administrations of diffractaic acid and olive oil attenuated the Ti-alloy implantation, and decreased superoxide dismutase activity and total glutathione level in peri-implant tissues. These results demonstrate that diffractaic acid and olive oil are involved in the induction of apoptotic cell death both through caspase-dependent cell death and as an antioxidant. Thus, the data suggest that both diffractaic acid and olive oil could be developed as effective proapoptotic agents in various disorders treatments.

Gastroprotective and Antioxidant Effects of Lobaria pulmonaria and Its Metabolite Rhizonyl Alcohol on Indomethacin‐Induced Gastric Ulcer

Two lichen metabolites, rhizonaldehyde (1) and rhizonyl alcohol (2), were isolated from the acetone extract of Lobaria pulmonaria by chromatographic methods, and their chemical structures were determined by UV/VIS, IR, and 1D‐ and 2D‐NMR spectroscopic methods. The gastroprotective and in vivo antioxidant activities of extracts of L. pulmonaria and its metabolites, 1 and 2, were investigated in indomethacin‐induced ulcer models in rats. The gastric lesions were significantly reduced by acetone, hexane, and CHCl3 extracts, with 75.3–41.5% inhibition. Rhizonyl alcohol (2) significantly reduced the gastric lesions with an inhibition rate of 84.6–42.8%, whereas rhizonaldehyde (1) significantly increased the gastric lesions. Antioxidant parameters and myeloperoxidase activities were also evaluated in the gastric tissues of the rats. Indomethacin caused oxidative stress, which resulted in lipid peroxidation in gastric tissues by decreasing the levels of the antioxidants as compared to healthy rat tissues. In contrast to indomethacin, all extracts and rhizonyl alcohol (2) caused a significant decrease in lipid peroxidation levels and an increase in antioxidant parameters, superoxide dismutase, glutathione peroxidase, and glutathione‐S‐transferase, and reduced glutathione in gastric tissues. The administration of rhizonyl alcohol (2) also resulted in a decrease in gastric myeloperoxidase activity increased by indomethacin. The gastroprotective effect of rhizonyl alcohol (2) can be attributed to its antioxidant properties and its suppressing effect on neutrophil infiltration into gastric tissues.

N-Acetyl Cysteine Has Both Gastro-Protective and Anti-Inflammatory Effects in Experimental Rat Models: Its Gastro-Protective Effect Is Related to Its In Vivo and In Vitro Antioxidant Properties

N‐acetyl cysteine (NAC), a metabolite of sulphur‐containing amino acid cysteine, is used as an antioxidant and a mucolytic agent. Therefore, we aimed to investigate anti‐inflammatory and anti‐ulcerative effects of NAC. We also intended to determine the relation between antiulcer effect of NAC and its antioxidant properties by biochemical evaluation. In this study a total of 15 rat groups (n = 6 per group) were used for inflammation and ulcer experiments. Anti‐inflammatory effects of NAC have been investigated on six rat groups with carrageenan (CAR)‐induced paw oedema model. Antiulcer effects of NAC have been investigated on 24 h fasted nine rat groups with IND‐induced ulcer model in the presence of positive (LAN, RAN, FAM, and OMEP), negative (untreated IND group) and intact control groups. In biochemical analyses of stomach tissues; glutathione S‐transferase (GST), catalase (CAT), myeloperoxidase (MPO), and superoxide dismutase (SOD) enzyme activities and lipid peroxidation (LPO) and the glutathione (GSH) levels were determined. All doses of NAC exerted significant anti‐inflammatory effect; even the effect of 900 mg/kg NAC was similar with that of DIC and IND. In gastric tissues NAC administration decreased the level of LPO and activity of CAT, which were increased by IND. Furthermore, NAC increased the GSH level and SOD and GST activities, which decreased in ulcerous stomach tissues. Only MPO activity increased in both IND and NAC groups when compared to healthy rat group. We determined that NAC has both anti‐inflammatory and anti‐ulcerative effects. J. Cell. Biochem. 117: 308–319, 2016.