Tuncay Altug

Selective nuclear factor κ‐B inhibitors, pyrolidium dithiocarbamate and sulfasalazine, prevent the nephrotoxicity induced by gentamicin

To investigate the effect of selective nuclear factor κ‐B (NFκ‐B) inhibitors, pyrolidium dithiocarbamate (PD) and sulfasalazine (SZ) on renal tubular necrosis and inducible nitric oxide synthase (iNOS) and NFκ‐B expression induced by gentamicin in rats.

Protective Effect of a Potent Antioxidant, Pomegranate Juice, in the Kidney of Rats with Nephrolithiasis Induced by Ethylene Glycol

PURPOSE We aimed to study the protective effects of pomegranate juice (PJ) on ethylene glycol (EG)-induced crystal deposition in renal tubules, renal toxicity, and inducible nitric oxide synthase (iNOS) and nuclear factor-kappaB activities in rat kidneys. MATERIALS AND METHODS Fifty-six rats were divided into four equal groups: Control, EG, EG + 50 microL PJ/d (PJ50), and EG + 100 microL PJ/d (PJ100). Rats were sacrified on days 10 and 45. Tissue sections were evaluated under light and polarized microscopy for the presence and degree of crystal deposition and toxicity in the kidneys. Crude extracts of the cortex were used to determine reduced gluthatione (GSH), nitric oxide (NO), and malondialdehyde (MDA) levels. RESULTS In the EG group, crystal depositions were more evident and mild crystalization was observed in proximal tubules on day 10; severe crystalization and granulovacuolar epithelial cell degeneration were observed on day 45. There was limited or no crystal formation in the EG + PJ-given groups. There were completely normal renal and tubular structures in the control group. There was no significant difference between the four groups in serum levels of sodium, potassium, blood urea nitrogen, and creatinine in any sampling time. Hyperoxaluria, a marked increase in MDA and NO levels, and decrease of GSH were observed in the EG-given groups compared with the others. There were marked iNOS and p65 expressions in only the EG-given rats compared with control and PJ groups, immunohistochemically. CONCLUSION This experiment shows the protective effect of PJ in the EG-induced crystal depositions in renal tubules.

Effect of vitamin C on oxidative liver injury due to isoniazid in rats

Background:  The aim of the present study was to investigate the effect of different doses of vitamin C on oxidative liver injury due to isoniazid (INH) in rats.

Influence of Tribulus terrestris extract on lipid profile and endothelial structure in developing atherosclerotic lesions in the aorta of rabbits on a high-cholesterol diet☆

The aim of this study was to investigate the pleotropic effects of an extract of a traditional herb, Tribulus terrestris (TT), on the lipid profile and vascular endothelium of the abdominal aorta in New Zealand rabbits fed a cholesterol-rich diet. Eighteen rabbits were randomly divided into three groups (n=6 for each). One experimental group (EG-I) was given a cholesterol-rich diet, a second experimental group (EG-II) was treated with TT following a cholesterol-rich diet, and a control group (CG) was fed a standard diet. Blood samples were collected on day 0 and then at weeks 4 and 12 to determine total serum cholesterol (TC), high density lipid-cholesterol (HDL-C), low density lipid-cholesterol (LDL-C) and triglyceride (TG) levels. Tissues were collected from the abdominal aorta for immunohistochemistry and transmission and scanning electron microscopy. In EG-II, the serum lipid profile was significantly lower than that of EG-I at week 12 with a reduction of TC: 65%; LDL-C: 66%; HDL-C: 64%; TG: 55%. Ultrastructural analysis revealed that endothelial damage was more prominent in EG-I compared to EG-II. The ruptured endothelial linings and damaged cellular surfaces increased in EG-I compared to EG-II. Our data indicate that dietary intake of TT can significantly lower serum lipid profiles, decrease endothelial cellular surface damage and rupture and may partially repair the endothelial dysfunction resulting from hyperlipidemia.

Oxidative damage to nuclear DNA in hyperthyroid rat liver: inability of vitamin C to prevent the damage.

The effects of hyperthyroidism on oxidative DNA damage in liver tissue and modification by vitamin C supplementation were investigated in rats. Animals were rendered hyperthyroid by administration of l-thyroxine (0.4 mg/100 g food) for 25 d. In the plasma samples, T3, T4, and thyroid-stimulating hormone (TSH) were measured by radioimmunoassay and ascorbate spectrophotometrically. Oxidative damage to hepatic nuclear DNA was determined by measuring deoxy-guanosine (dG) and 8-oxodG by high-performance liquid chromatography with diode array detector electrochemical detection (HPLC-DAD-ECD). In hyperthyroidism, 8-oxodG/ (105 dG) levels were significantly higher and plasma vitamin C levels lower than in control rats. The results of this experimental study show that oxidative damage to hepatic nuclear DNA increases in the hyperthyroid state and that vitamin C was not effective in preventing this damage.

Effects of Crataegus microphylla on vascular dysfunction in streptozotocin-induced diabetic rats.

Vascular dysfunction plays a key role in the pathogenesis of diabetic vascular disease. In this study, we aimed to investigate whether chronic in vivo treatment of Crataegus microphylla (CM) extract in diabetic rats induced with streptozotocin (STZ, intraperitoneal, 65 mg/kg) preserves vascular function and to evaluate whether the reduction of inducible nitric oxide synthase (iNOS), proinflammatory cytokines, and lipid peroxidation mediates its mechanisms of action. Starting at 4 weeks of diabetes, CM extract (100 mg/kg) was administrated to diabetic rats for 4 weeks. In aortic rings, relaxation to acetylcholine and vasoreactivity to noradrenaline were impaired, whereas aortic iNOS expression and plasma tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6), total nitrite–nitrate, and malondialdehite levels were increased in diabetic rats compared with controls. Chronic CM treatment significantly corrected all the above abnormalities in diabetic rats. In comparison, pretreatment of the aorta of diabetic rats with N‐[3(aminomethyl) benzyl]‐acetamidine, dihydrochloride (10–5 M), a selective inhibitor of iNOS, produced a similar recovery in vascular reactivity. These results suggest that chronic in vivo treatment of CM preserves endothelium‐dependent relaxation and vascular contraction in STZ‐induced diabetes, possibly by reducing iNOS expression in the aorta and by decreasing plasma levels of TNF‐α and IL‐6 and by preventing lipid peroxidation. Copyright

Suppression of Atherogenesis by n-3 Fatty Acids in the Cholesterol-Fed Rabbit

The effects of n-3 fatty-acid supplementation on serum lipids, platelet aggre gation, and the development of atherosclerotic lesions were studied in the choles terol-fed rabbit. Serum total cholesterol and LDL cholesterol values were significantly reduced in comparison with those of the nonsupplemented choles terol-fed group (p<0.005, p<0.0025, respectively), though still higher than those of the control group (p<0.0025, p<0.0125 respectively). Platelet aggregation was reduced below that of the cholesterol-fed and the control levels (p<0.0005, p<0.0025, respectively). The endothelial injury encountered in cholesterol-fed rabbits was inhibited in the supplemented group. It is concluded that n-3 fatty acids suppress atherogenesis in this animal model by interfering with platelet aggregation and lipid metabolism.

Pyrolidium dithiocarbamate prevents shockwave lithotripsy-induced renal injury through inhibition of nuclear factor-kappa B and inducible nitric oxide synthase activity in rats.

PURPOSE Extracorporeal shockwave lithotripsy (SWL) is commonly used for treatment of renal stones. Free oxygen radicals are involved in the pathophysiology of renal injury due to SWL. We investigated the protective effect of pyrolidium dithiocarbamate (PDTC), an antioxidant and nuclear factor kappa-B (NFkappa-B) inhibitor, against renal injury. MATERIALS AND METHODS Forty-eight rats were divided into three groups: group 1, controls; group 2, SWL (15 kW, 1500 pulses); and group 3, SWL + pyrolidium dithiocarbamate (PDTC) (100 mg/kg/day given intraperitoneally 1 day before and 5 days after SWL). The rats were sacrificed and their kidneys were removed on days 7 and 35 after SWL. Samples were fixed in formaldehyde solution, and renal tissues were examined for proximal tubular injury under light microscopy. iNOS activity and active subunit of NFkappa-B, p65, were evaluated immunohistochemically using rat monoclonal antibodies interpreting results semiquantitatively. RESULTS There were significant differences between SWL and control groups on days 7 and 35, considering histological changes under light microscope (p < 0.02). There was significant decrease in necrosis and fibrosis in PDTC group compared to SWL group. Expression of inducible nitric oxide synthase (iNOS) and p65 on days 7 and 35 were at basal levels as seen with immunohistochemical staining. There were high concentrations of iNOS and p65 in the SWL group (P < 0.02). No significant difference in concentrations was seen between the control and the PDTC groups (P > 0.02). CONCLUSION We found that curcumin decreased the expression of iNOS, p65, and serum nitric oxide levels, and helped prevent interstitial, glomerular, tubular epithelial, and endothelial cellular injury. We believe that PDTC could be used, particularly in high-risk patients, as a protective agent against renal injury due to SWL.

VITAMIN E SUPPLEMENTATION IN STREPTOZOTOCIN-TREATED RATS ALTERS CEREBELLAR AND PLASMA NITRIC OXIDE METABOLISM

Nitric oxide (NO) free radicals appear to contribute to the pathogenesis of a number of disorders including diabetes mellitus. The aim of this study was to determine the effects of streptozotocin (STZ)-induced diabetes on nitric oxide (NO) metabolites in plasma and cerebellar nitric oxide synthase (NOS) activity. Further, it was of interest to determine whether an antioxidant, vitamin E, could reverse the STZ-induced effects. STZ significantly decreased cerebellar NOS but increased the level of plasma total nitrite + nitrate and the level of plasma nitrate. Supplementation with vitamin E effectively reduced the STZ-induced effects. Data demonstrate that vitamin E may serve as a protective antioxidant in STZ-induced diabetes.

PSORIASIS‐LIKE LESIONS IN GUINEA PIGS RECEIVING PROPRANOLOL

Background. β‐Blockers cause a psoriasiform eruption. We investigated the skin effects of systemic propranolol in a formal protocol.