The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

The fibrinogen to albumin ratio is significantly associated with ischemic RVO. Instead of complicated and invasive methods, such as a retinal angiogram, the fibrinogen to albumin ratio could be a useful initial diagnostic test to predict ischemia in RVO.

Rosmarinic acid (RA) is a natural polyphenolic compound derived from many common herbal plants. Although it is known that RA has many important biological activities, its effect on proteasome inhibitor-induced changes in cancer treatment or its effects on any experimental proteasome inhibition model is unknown. The aim of the study was to investigate the effect of RA on MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. HepG2 cells were treated with 10, 100, and 1000 µM RA in the presence of MG132 for 24 h; 10 and 100 µM RA did not affect but 1000 µM RA decreased cell viability in HepG2 cells. MG132 caused a significant decrease in cell viability and phosphorylation of mammalian target of rapamycin and a significant increase in levels of polyubiquitinated protein, microtubule-associated proteins 1A/1B light chain 3B-II (LC3B-II), heat shock protein 70 (HSP70), binding immunoglobulin protein (BiP), activating transcription factor 4 (ATF4), protein carbonyl, and cleaved poly(adenosine diphosphate-ribose) polymerase 1 (PARP1); 10 and 100 µM RA did not significantly change these effects of MG132 in HepG2 cells; 1000 µM RA caused a significant decrease in cell viability and a significant increase in polyubiquitinated protein, LC3B-II, HSP70, BiP, ATF4, protein carbonyl, and cleaved PARP1 levels in MG132-treated cells. Our study showed that only 1000 µM RA increased MG132-induced cytotoxicity, proteasome inhibition, autophagy, cellular stresses, and apoptosis in HepG2 cells. According to our results, cytotoxic concentration of RA can potentiate the effects of MG132 in hepatocellular carcinoma treatment.

We investigated the effects of quercetin on pathological findings on testicular ischaemia-reperfusion (I/R) injury in rats. Twenty-four male Wistar albino rats were randomly assigned into four groups: Group 1, control (n = 5); Group 2, sham (n = 4); Group 3, I/R (n = 8); and Group 4, I/R + quercetin (n = 7). Bilateral testicular artery and vein were occluded for 1 h, followed by reperfusion in I/R and I/R + quercetin animals. Quercetin (20 mg kg(-1) per day) was administrated once daily by gavage to Group 1 and Group 4, respectively, after reperfusion. At the end of the study, bilateral orchiectomies were performed for histopathologic examination. The tissue damage was evaluated with light microscopy. Normal inter-stitium and seminiferous tubules were observed in control group. In the sham group, rats were seen minimal oedema around the seminiferous tubules and congested vascular structures. In Group 3, oedema, vascular congestion and haemorrhage between seminiferous tubules were observed. In Group 4, histopathologic features were markedly less than Group 3 (P = 0.03). Our study demonstrated that quercetin seems to have a protective effect on testis histopathology in rats with testicular I/R.

Objective: The aim of this study was to investigate the protective effect of L-carnitine against to liver damage caused by lipid peroxidation and oxidative stress in toxic hepatitis induced by acetaminophen. Materials and Methods:Wister-albino male rats were divided into three groups randomly: control, toxic hepatitis, and L-carnitine groups. To introduce a toxic hepatitis, single dose of acetaminophen (300 mg/kg) dissolved in warm saline was given intraperitoneally to toxic hepatitis and L-carnitine groups. A single dose of L-carnitine (500 mg/kg) was given intraperitoneally to L-carnitine group five minutes after introducing to toxic hepatitits. A single dose of warm saline was given intraperitoneally to control group. Results: In toxic hepatitis group, serum alanine and aspartate aminotransferase and plasma and liver malondialdehyde levels were higher whereas plasma Gc-globulin, whole blood and liver glutathione levels, erythrocyte and liver catalase activities and erythrocyte glutathione peroxidase activity were lower as compared to control group. In L-carnitine group, serum alanine and aspartate aminotransferase and plasma and liver malondialdehyde levels were lower whereas whole blood and liver glutathione levels, erythrocyte and liver catalase activities and erythrocyte glutathione peroxidase activity were higher as compared to toxic hepatitis group. There was no significant change between plasma Gc-Globulin levels of these groups. Histopathological changes in toxic hepatitis group were more prominent than those found in L-carnitine group. Conclusion: L-Carnitine has a protective effect against to liver damage caused by lipid peroxidation and oxidative stress in toxic hepatitis induced by acetaminopfen in rats.

ÖZETAmaç: Oksidatif stres inflamatuvar barsak hastalıklarının patogenezinde önemli rol oynar. Bu çalışmada, antioksidan L-karnitinin deneysel kolitte, kolonda da sentez edilen paraoksonaz 1 enzim aktivitelerine ve oksidatif duruma etkisini inceledik. Gereç ve Yöntem: Wistar albino dişi sıçanlar kontrol, kolit, ön tedavi ve tedavi olmak üzere rastgele dört gruba ayrıldı. Kolit oluşturmak için kolit, tedavi ve ön tedavi gruplarına tek doz 1 mL asetik asit (%4) intrarektal olarak uygulandı. Ön tedavi grubuna kolit oluşturulmadan 1 saat önce, tedavi grubuna ise kolit oluşturulduktan 24 saat sonra 500 mg/kg L-karnitin tek doz halinde intraperitoneal olarak verildi. Tüm gruplar intrarektal uygulamadan 48 saat sonra sakrifiye edildi. Kolit varlığı histopatolojik olarak gösterildi. Serumda paraoksonaz, arilesteraz ve laktonaz aktiviteleri, total oksidan ve antioksidan durum, malondialdehit ve total sialik asit ölçüldü. Oksidatif stres indeksi formülden hesaplandı. Bulgular: Asetik asitle kolit oluşturulan grupta serum malondialdehit, total sialik asit, total oksidan durum ve oksidatif stres indeksi anlamlı olarak artarken, paraoksonaz, arilesteraz ve laktonaz aktiviteleri ve total antioksidan durum anlamlı olarak azaldı. L-Karnitin malondialdehit, total sialik asit, total oksidan durum ve oksidatif stres indeksinde anlamlı bir azalmaya yol açarken, sadece tedavi grubunun serum arilesteraz ve laktonaz aktivitelerinde anlamlı bir artışa yol açtı. Sonuç: Asetik asitle oluşturulan deneysel kolitte L-karnitin, arilesteraz ve laktonaz aktivitelerini arttırıcı, oksidatif stresi azaltıcı bir etkiye sahiptir. Bu nedenle L-karnitin, inflamatuvar barsak hastalıklarının tedavisinde yararlı olabilir. Anahtar Sözcükler: Deneysel kolit, L-karnitin, paraoksonaz, arilesteraz, laktonaz, oksidatif stres, malondialdehit, total sialik asit Çıkar Çatışması: Yazarlar arasında çıkar çatışması yoktur. ABSTRACT Aim:Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease. We investigated antioxidant L-carnitine effect on activities of paraoxonase 1 enzyme which is also synthesized in colon and oxidative status in experimental colitis. Material and Methods: Wistar albino female rats were divided into four groups randomly: control, colitis, pre-treatment and treatment groups. To induce colitis, single dose of 1 mL acetic acid (%4) was given intrarectally to colitis, pre-treatment and treatment groups. Single dose of 500 mg/kg L-carnitine was given intraperitoneally 1 hour before inducing colitis to pre-treatment group and 24 hours after inducing colitis to treatment group. All groups were sacrificied 48 hours after intrarectally administration. Existence of colitis was confirmed by histopathological changes. Paraoxonase, arylesterase and lactonase activities, total oxidant and antioxidant status, malondialdehyde, and total sialic acid were measured in serum. Oxidative stress index was calculated from the formula. Results: While serum malondialdehyde, total sialic acid, total oxidant status and oxidative stress ind...

Paraoxonase-1 (PON1) and PON3 (PON3) are anti-atherosclerotic enzymes, synthesized primarily in liver and bound to HDL in circulation. The aim of the present study was to investigate the effects of therapeutic doses of lipoic acid on PON1 and PON3 protein levels, mRNA expression and arylesterase activity in liver. We treated HepG2 cells with 10, 40 and 200 μM lipoic acid for 72 h. Cell viability was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. PON1 and PON3 protein levels were measured by Western blotting, their mRNA expression was measured by quantitative PCR and arylesterase activity was measured spectrophotometrically. 200 µM lipoic acid caused a significant increase on PON1 and PON3 protein levels and arylesterase activity as compared with control, 10 µM and 40 µM lipoic acid-treated cells. 200 µM lipoic acid also caused a significant decrease on PON1 mRNA expression whereas on a significant increase PON3 mRNA expression as compared with control, 10 µM and 40 µM lipoic acid-treated cells. Our study showed that although lipoic acid up-regulates PON3 but down-regulates PON1 mRNA expression, it increases both PON1 and PON3 protein levels and arylesterase activity in HepG2 cells. We can report that lipoic acid may be useful for preventing atherosclerosis at therapeutic doses.

OBJECTIVES: We aimed to investigate the effect of lipoic acid in the prevention of myocardial infarction in diabetic rats. METHODS: Rats were divided into fi ve groups as control, ISO, LA+ISO, STZ+ISO and STZ+LA+ISO. To induce diabetes, single dose of streptozotocin was injected to STZ+ISO and STZ+LA+ISO groups. Lipoic acid (10 mg/ kg/day) was injected for 14 days to LA+ISO and STZ+LA+ISO groups. To induce myocardial infarction, isoproterenol was injected to ISO, LA+ISO, STZ+ISO and STZ+LA+ISO groups on the days 13 and 14 of lipoic acid treatment. Cardiac necrosis and leucocyte infi ltration were investigated histopathologically. Serum malondialdehyde levels, paraoxonase and lactonase activities were measured spectrophotometrically. RESULTS: Isoproterenol caused a signifi cant increase in cardiac necrosis, leucocyte infi ltration and serum lipid peroxidation whereas a signifi cant decrease in serum paraoxonase and lactonase activities. In myocardial infarcted non-diabetic rats, while lipoic acid caused a signifi cant decrease in cardiac necrosis, leucocyte infi ltration and serum lipid peroxidation and a signifi cant increase in serum paraoxonase and lactonase activities, it did not change these histopathologic or biochemical parameters in myocardial infarcted diabetic rats. CONCLUSION: Lipoic acid, at the dose of 10 mg/kg, is effective to prevent myocardial infarction in non-diabetic rats but it is insuffi cient in diabetic rats (Tab. 1, Fig. 2, Ref. 35).