Mehmet Kaya Ozer

Aim: To determine the potential musculoprotective effects of thymoquinone (TQ) on valproic acid (VPA)-induced muscle damage. Materials and Methods: Twenty-one male Spraque-Dawley rats were randomly separated into 3 groups (n = 7): Control, VPA, VPA + TQ. Oral VPA (500 mg/kg/day) and TQ (50 mg/kg/day) were given to the rats for a period of 14 days. On the 15th day, soleus muscle tissues were taken for evaluating the expression levels of the Alpha-actinin-3 (ACTN3) and Myosin heavy chain 7 (MYH7) genes and histological analysis. Results: The VPA + TQ group showed significantly higher ACTN3 and lower MYH7 gene expression, and decreased NADPH oxidase-4 (NOX4) and caspase-3 (CAS-3) levels than the VPA group. Also, histopathological changes were decreased in the VPA + TQ group in comparison with the VPA group. Conclusion: VPA-induced soleus muscle damage was alleviated due to the antioxidant and antiapoptotic effects of TQ. TQ may be beneficial in treating soleus muscle damage caused by VPA.

It is assumed that excessive fructose consumption is associated with the risk of developing various diseases, especially metabolic disease. The aims of this study were two fold: 1) Does liver and pancreatic damage occur due to excessive fructose consumption 2) If damage occurs, can we reduce this damage by using (ASA) and Vit. C. The rats were divided randomly into five groups of eight as follows: Group1-control; Group2-corn syrup (Fructose: F; 30% F solution); Group3-F and ASA (F+10 mg/kg/day, ASA, oral); Group4-F and Vit. C (F+200 mg/kg/day, Vit. C, oral); Group5-F, ASA and Vit C (F+A+C -same dose administration, respectively). The rats were sacrificed 24 h after the last application at the end of the 6th week, and their blood serum, liver and pancreas tissues were taken and evaluated histologically and biochemically. It was found that serum cholesterol and AST levels were significantly lower in the F+C and F+A+C groups, and ALT and TG levels were significantly lower in the F+A+C group compared to the F group (p

We investigated the potential neuroprotective effects of thymoquinone (TQ) on amikacin (AK) induced oxidative damage in rat brain. We used 21 male rats divided randomly into three equal groups. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% aqueous NaCl and given 1 ml 0.9% aqueous NaCl orally. The AK group was administered 1.2 g/kg aqueous AK i.p. as a single dose on the day 3 of the study. The AK + TQ group was given a single 1.2 g/kg dose of AK i.p. on the day 3 of the study plus 40 mg/kg/day TQ by oral gavage daily. Treatment with TQ increased serum ferritin and decreased serum calcium levels significantly. TQ also decreased NADPH oxidase-2, NADPH oxidase-4, and caspase-3 levels. Decreased malondialdehyde (MDA) levels and increased superoxide dismutase (SOD) and catalase (CAT) activities were detected in the AK + TQ group compared to the AK group. TQ administration inhibited lipid peroxide formation and blocked oxidative reactions, which reduced the MDA level and increased SOD and CAT activities induced by AK. Oxidative damage caused by AK was ameliorated by TQ treatment owing to its antioxidative and anti-apoptotic effects. TQ may be a potential therapeutic agent for reducing the severity of AK induced oxidative damage to the brain.

Amaç: Bu çalışmanın amacı timokinonun (TQ) valproik asit (VPA) kaynaklı pankreas hasarını önleme veya tedavi etmedeki potansiyel etkisinin, sıçanların pankreas dokusundaki gen ekspresyonlarının ve histopatolojik değişikliklerin değerlendirilmesidir. Gereç ve Yöntem: 21 erkek Spraque-Dawley sıçanı 3 gruba ayrıldı (n = 7): Kontrol, VPA, VPA + TQ. Sıçanlar, 14 gün boyunca oral yoldan VPA (500 mg/kg/gün) ve TQ (50 mg/kg/gün) ile muamele edildi. Muamelenin 15. gününde, histon deasetilaz (HDAC1 ve HDAC2) genlerinin ekspresyon seviyelerinin analizi için pankreas dokusu çıkarıldı. Pankreas dokularındaki yapısal değişiklikler incelendi. Bulgular: VPA + TQ grubunun, VPA grubuna göre anlamlı derecede daha yüksek HDAC1 ve HDAC2 gen ekspresyonuna sahip olduğu görüldü. Ayrıca bulgularımız, TQ tedavisinin pankreas dokusunu VPA'nın HDAC1 ve HDAC2 gen ekspresyonu üzerindeki olumsuz etkilerine karşı koruyabildiğini göstermektedir. Ayrıca TQ NADPH oksidaz-4 (NOX-4) ve kaspaz-3 (CAS-3) düzeylerini de düşürdü. VPA+TQ grubunda VPA grubuna göre oksidatif stres azaldı, antioksidan aktivite arttı ve histopatolojik değişiklikler azaldı. VPA'nın neden olduğu pankreas hasarı, TQ'nun antioksidatif ve antiapoptotik etkileri nedeniyle hafifletildi. Sonuç: TQ, VPA'nın neden olduğu pankreas hasarının şiddetini azaltmada faydalı olabilir.

Bleomycin (BLM) is a chemotherapeutic agent that can cause pulmonary fibrosis. Little is known about the possible protective role of the CB2 receptor agonist, AM1241. We investigated the effects of CB2 receptor activation by AM1241 on BLM induced lung fibrosis in a rat model. BLM was administered via the trachea. Adult female Wistar rats were divided into five groups: saline (control group), BLM (BLM group), CB2 agonist (AM1241) + BLM (BLMA group), CB2 antagonist (AM630) and CB2 agonist (AM1241) + BLM (BLMA + A group), and vehicle (dimethylsulfoxide) + BLM (BLM + vehicle group). Hydroxyproline, collagen type 1, total protein, glutathione (GSH), malondialdehyde (MDA), interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels were measured in lung fibrosis and control tissue using standard methods. We investigated the histopathology of lung tissue to determine the extent of fibrosis. We found significantly higher levels of hydroxyproline, TNF-α, IL-6 and total protein in the BLM group compared to the BLMA group. The level of GSH also was higher in the BLMA group compared to the BLM group. Inflammation and fibrotic changes were significantly reduced in the BLMA group. Our findings suggest that CB2 receptor activation provided protection against BLM induced pulmonary fibrosis by suppressing oxidative stress and increasing cytokines.

We investigated the potential cardioprotective effects of misoprostol (MP) on doxorubicin (DOX) induced cardiac damage using histologic and biochemical assessment of rat heart. We used 21 male rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was given 0.5 ml 0.9% NaCl intraperitoneally (i.p.) and 1 ml 0.9% NaCl orally for 6 days. DOX was administered as a single dose of 20 mg/kg i.p. on day 3. MP was administered orally for 6 days. We found that treatment with MP decreased significantly serum cardiac troponin-I, brain natriuretic peptide levels, and lactate dehydrogenase, aspartate aminotransferase, alanine transaminase and creatine kinase isoenzyme-MB activities. DOX increased the malondialdehyde level and decreased the catalase, superoxide dismutase activities and glutathione levels; MP prevented these alterations. MP also decreased NADPH oxidase-4 and caspase-3 levels. In the DOX + MP group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were decreased compared to the DOX group. Cardiac damage caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP. MP may be useful for reducing the severity of DOX induced damage.

We investigated whether thymoquinone (TQ) exerts a beneficial effect on renal injury due to amikacin (AK) administration in rats. To generate kidney damage with AK, a single 1.2 g/kg dose of AK was administered intraperitoneally. TQ was administered orally to the AK treated group at a dose of 40 mg/kg for five days. At the end of the experiment, rats were sacrificed and blood samples were used to measure blood urea nitrogen (BUN) and creatinine (Cr) levels. Kidney samples were taken to measure the oxidative stress biomarker, malondialdehyde (MDA), and expression of the antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT). Because reactive oxygen species (ROS) and apoptosis contribute to tissue damage associated with NADPH oxidase (NOX), we also investigated NOX-2, NOX-4 and apoptosis marker, caspase-3, expression using immunohistochemistry. MDA, BUN, Cr, NOX-2, NOX-4 and caspase-3 production were increased, and SOD and CAT were decreased in the AK treated group compared to controls. MDA, BUN, Cr, NOX-2, NOX-4 and caspase-3 levels were decreased, and SOD and CAT levels were increased in TQ + AK treated rats compared to AK treated animals. TQ appears to protect the kidney from the toxic effects of AK.

Purpose: The aim of this study was to investigate the protective effect of resveratrol (RSV) against risperidone (RIS) on weight gain/loss via of the expression of some various neurotransmitter receptors. Materials and Methods: Thirty five female Spraque-Dawley rats were divided into 5 groups (n=7): Control, RIS, RIS+RSV-1, RIS+RSV-2, RIS+RSV-3. Rats were treated orally with RIS (2 mg/kg/day) and RSV (20, 40 and 80 mg/kg/day) for 14 days. On treatment day 15, blood and brain tissues were removed for analysis. Results: The reduced neuropeptide Y1 expression levels in the RSV groups correlated with the RSV-induced weight loss. The Dopamine D1 receptor and seratonin 5-HT2c expression levels decreased significantly with RSV treatment. In addition, the RSV increased the glucose, triiodothyronine, tetraiodothyronine, and total antioxidant status, and decreased the cholesterol, triglyceride, high density lipoproteins, low density lipoproteins, thyroid-stimulating hormone, oxidative stress index, and total oxidant status levels significantly. Conclusion: The daily treatment with RSV increased the antioxidant capacity, protected the apoptotic cell injury, and the possibility of death. RSV could be an effective course of therapy to enhance therapeutic efficacy.

Objective. The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments.Materials and Methods. Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n= 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n= 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n= 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n= 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n= 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis.Results. The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly (p< 0.05).Conclusion. This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose‐induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS‐fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption‐induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS‐induced cardiovascular abnormalities could be prevented by CAPE treatment.