Effect of taxifolin on methanol-induced oxidative and inflammatory optic nerve damage in rats.

Purpose: Oxidative stress and inflammation have been demonstrated in the pathogenesis of methanol toxicity. Taxifolin has antioxidant and anti-inflammatory properties. In this study, we examined the protective effect of taxifolin against methanol-induced optic nerve toxicity. Materials and methods: Animals were divided into four groups (n = 6): healthy control group (HG), methotrexate (MTX) treated group, methotrexate + methanol treated group (MTX + M), and methotrexate + methanol + taxifolin treated group (MTX + M+T). MTX was administered to all groups except HG group 3 mg/kg via oral gavage for 7 d. After that 20% methanol was orally administered to the MTX + M and MTX + M+T group at a dose of 3 g/kg. After 4 h, taxifolin was orally administered to MTX + M+T group 50 mg/kg. Animals were sacrificed by high-dose thiopental anaesthesia, 8 h after taxifolin administration and biochemical studies were performed. Results: Malondialdehyde (MDA), total oxidant system, nuclear factor kappa B (NF-κB), and tumour necrosis factor-alpha levels were significantly higher in the optic nerve of MTX and MTX + M groups compared to HG group. Otherwise, total glutathione (tGSH) and total antioxidant system levels decreased in MTX and MTX + M groups according to the HG group. MDA, total oxidant system, NF-κB, and tumour necrosis factor-alpha levels were decreased in the MTX + M+T group and tGSH, and total antioxidant system levels increased in the MTX + M+T group according to the MTX + M group. Conclusions: These results indicate that taxifolin prevents oxidative and inflammatory optic nerve damage due to methanol exposure.

Effect of taxifolin on development of retinopathy in alloxan-induced diabetic rats.

Purpose: Diabetic retinopathy (DR) is one of the leading causes of blindness. In DR patients, antioxidant defence is disrupted, and production of reactive oxygen species and pro-inflammatory cytokines such as interleukin 1ß (IL-1ß) and tumour necrosis factor alpha (TNF-α) increases. Taxifolin has been reported to suppress reactive oxygen species, IL-1ß and TNF-α production. The aim of this study is to biochemically and histopathologically examine the protective effect of taxifolin against DR damage induced by alloxan. Materials and methods: Alloxan received rats with a blood glucose level of ≥250 mg/dL were divided into taxifolin-treated (TAX) (n = 6), diabetic control (DC) (n = 6) groups. There were rats received only saline in non-diabetic control (NC) group (n = 6). Taxifolin (50 mg/kg) was orally administered to the TAX group rats. DC and NC rats received the same volume of saline as a solvent. This procedure was repeated once a day for 3 months. At the end of this period, animals were killed by high dose thiopental sodium anaesthesia. Histopathological examinations were then performed on excised rat eyes. Malondialdehyde (MDA), total glutathione (tGSH), IL-1ß and TNF-α levels were measured in obtained blood samples. Results: MDA, IL-1ß and TNF-α levels were significantly increased in blood samples of DC group rats with hyperglycemia induced by alloxan compared with NC group (p < 0.0001), and decreased in the TAX group compared with the DC group (p < 0.0001). The levels of tGSH were significantly decreased in blood samples of DC group rats compared with NC group (p < 0.0001), and increased in the TAX group compared with the DC group (p < 0.0001). Histopathologically, retinal ganglion cells of the TAX group had a slightly dilated and congested blood vessel, and severe damage was inflicted to the retinal ganglion cell layer of the DC group. Conclusions: Experimental results suggest that taxifolin may be beneficial in the treatment of DR.

Synthesis of 2-amino-3-cyanopyridine derivatives and investigation of their carbonic anhydrase inhibition effects.

The conversion of carbon dioxide (CO2 ) and bicarbonate (HCO3- ) to each other is very important for living metabolism. Carbonic anhydrase (CA, E.C.4.2.1.1), a metalloenzyme familly, catalyzes the interconversion of these ions (CO2 and HCO3- ) and are very common in living organisms. In this study, a series of novel 2-amino-3-cyanopyridines supported with some functional groups was synthesized and tested as potential inhibition effects against both cytosolic human CA I and II isoenzymes (hCA I and II) using by Sepharose-4B-l-tyrosine-sulfanilamide affinity chromatography. The structural elucidations of novel 2-amino-3-cyanopyridines were achieved by NMR, IR, and elemental analyses. Ki values of the novel synthesized compounds were found in range of 2.84-112.44 µM against hCA I and 2.56-31.17 µM against hCA II isoenzyme. While compound 7d showed the best inhibition activity against hCA I (Ki : 2.84 µM), the compound 7b demonstrated the best inhibition profile against hCA II isoenzyme (Ki : 2.56 µM).

The effect of diabetes on ovaries in a rat model: the role of interleukin-33 and apoptosis.

Interleukin-33 (IL-33) is a novel cytokine involved in diabetes mellitus (DM) but its role in diabetic ovarian injury is unknown. As IL-33 is modulated by apoptosis, we aimed at investigating the effect of diabetes on ovaries in terms of evaluating apoptosis and IL-33 in a rat model. In this prospective experimental study, 16 female, nonpregnant Sprague-Dawley albino rats (12 weeks, 220-240 g) were randomly divided into two groups. Group 1 included eight healthy nondiabetic rats as controls and group 2 included eight rats in which diabetes was induced by intraperitoneal (i.p) injection of streptozotocin (STZ). After overt DM occurred (blood glucose >400 mgr/dl), all animals were euthanized and blood samples were collected by cardiac puncture for biochemical analysis. Bilateral oophorectomy was performed for histopathological examination. Serum levels of IL-33 and ovarian IL-33 and caspase-3 immunoexpressions were assessed. Immunoexpressions of caspase-3 and IL-33 were significantly higher in ovarian stromal cells of the diabetic rats compared to the controls. Also, in diabetic group, serum IL33 levels were significantly higher than the control group. In conclusion, increased IL-33 was observed both in serum and ovaries of STZ-induced diabetic rats as well as increased apoptosis in these diabetic rats. IL-33 may contribute to the apoptosis in diabetic ovarian injury.

Serum levels of soluble interleukin-2 receptor in association with oxidative stress index in patients with different types of HPV.

OBJECTIVES: The aim of this paper is to determine the oxidative-antioxidative status and levels of soluble interleukin-2 recep-tor (sIL-2R) in serum of patients with different types of HPV infections and to compare it with patients who are negative for HPV. MATERIAL AND METHODS: A total of 80 women were divided into three groups as follows: Group 1 consisted of 25 women who were positive for HPV types 16 or 18; Group 2 consisted of 25 women who were positive for other types of HPV includ-ing type 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 or 68; Group 3 consisted of 30 patients who were negative for HPV as a control group. Serum sIL-2R and plasma oxidative stress index (OSI) were analyzed. RESULTS: Serum sIL-2R levels were significantly higher in group 1 compared to group 2 and 3. OSI was found significantly increased in groups 1 and 2 compared to group 3. Also, we found a weak positive correlation between IL-2R and OSI. CONCLUSION: sIL-2R and oxidative stress may have a role in HPV infection, especially in case of high-risk types.

The effect of melatonin on oxidative stress and apoptosis in experimental diabetes mellitus-related ovarian injury.

We aimed to evaluate the effect of melatonin on oxidative stress and ovarian injury in rats. Twenty-four Sprague-Dawley albino rats were divided into three groups: Group 1 as nondiabetic healthy controls (n = 8), group 2 as nontreated diabetic rats (n = 8) and group 3 as melatonin-treated diabetic rats (n = 8). After overt diabetes was produced by intraperitoneal injection of streptozosin, 20 mg/kg/day of melatonin was given intraperitoneally to group 3 for a week. NF-kB and caspase-3 immunoexpressions, lipid peroxidation, the activities of antioxidative enzymes, total oxidant capacity and total antioxidant capacity were assessed. Immunoexpressions of NF-kB and caspase-3 were significantly lower in group 3 than group 2. There was a significant decrease in superoxide dismutase activity in group 2 than group 1 and a significant increase in group 3 compared with group 2. We observed a nonsignificant decrease in catalase activity between group 1 and group 2 and a nonsignificant increase between group 2 and group 3. There was a nonsignificant increase in the plasma level of total oxidant status in group 2 than group 1, but a significant decrease was observed in group 3 compared to group 2. Total antioxidant status was significantly lower in group 2 compared with group 1 and group 3. In conclusion, melatonin ameliorates the negative effects of oxidative stress on DM-related ovarian injury.

A compendium of expression patterns of cholesterol biosynthetic enzymes in the mouse embryo.

Cholesterol and its biosynthetic pathway intermediates and derivatives are required for many developmental processes including membrane biogenesis, transmembrane receptor signaling, steroid biogenesis, nuclear receptor activation, and posttranslational modification of hedgehog (Hh) proteins. To perform such multifaceted tasks depends on stringent regulation of expression of cholesterol biosynthetic enzymes (CBEs). We established for a whole organism, for the first time, the 3D expression pattern of all genes required for cholesterol biosynthesis (CBS), starting from acetyl-CoA and ending with cholesterol. This data was produced by high-throughput in situ hybridization on serial sections through the mouse fetus. The textually annotated image data were seamlessly integrated into the METscout and GenePaint public databases. This novel information helps in the understanding of why CBEs are expressed at particular locations within the fetus. For example, strong CBE expression is detected at sites of cell proliferation and also where cell growth increases membrane surface, such as in neurons sprouting axons and forming synapses. The CBE data also sheds light on the spatial relationship of cells and tissue that express sonic Hh (Shh) and produce cholesterol, respectively. We discovered that not all cells expressing Shh are capable of CBS. This finding suggests novel ways by which cholesterylation of Shh is regulated.

Inhibition profile of a series of phenolic acids on bovine lactoperoxidase enzyme.

Lactoperoxidase (LPO) catalyzes the oxidation of numerous of organic and inorganic substrates by hydrogen peroxide. It has very vital activity in the innate immune system by decreasing or stopping the activation of the bacteria in milk and mucosal secretions. This study's purpose was to investigate in vitro effect of some phenolic acids (ellagic, gallic, ferulic, caffeic, quercetin, p-coumaric, syringic, catechol and epicatechin) on the purified LPO. This enzyme was purified from milk by using different methods such as Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange and Sephadex G-100 gel filtration chromatography. LPO was purified 28.7-fold with a yield of 20.03%. We found phenolic acids have inhibition effects on bovine LPO enzyme to different concentrations. Our study showed lower concentrations of caffeic acid, ferulic acid and quercetin exhibited much higher inhibitory effect on enzyme, so these three of them were clearly a more potent inhibitor than the others were. All of compounds were non-competitive inhibitors.

The investigation of plasma glucose-6-phosphate dehydrogenase, 6-phoshogluconate dehydrogenase, glutathione reductase in premenauposal patients with iron deficiency anemia.

BACKGROUND AND OBJECTIVE: Iron is an essential element that is necessary for all cells in the body. Iron deficiency anemia (IDA) is one of the most common nutritional disorders in both developed and developing countries. The glutathione pathway is paramount to antioxidant defense and glucose-6-phosphate dehydrogenase (G6PD)-deficient cells do not cope well with oxidative damage. The goal of this study was to check the activities of G6PD, 6-phosphogluconate dehydrogenase, glutathione reductase in patients with IDA. METHODS: We analyzed the plasma samples of 102 premenopausal women with IDA and 88 healthy control subjects. Glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activity as compared to the reduction of NADP +, glutathione reductase activity was performed based on the oxidation of NADPH. 2 ml of plasma were used in all analyzes. SPSS program was used for all of the statistical analysis. RESULT: Diagnosis of iron deficiency in patients belonging to the analysis of blood were ferritin 3.60 ± 2.7 ng / mL, hemoglobin 9.4 ± 1.5 mg / dl and hematocrit 30.7 ± 4.1% ratio; in healthy subjects ferritin 53.5 ± 41.7 ng/ml, hemoglobin level 13.9 ± 1.3 mg / dl and hematocrit ratio 42 ± 3.53%. When compared to healthy subjects the glutathione reductase level (P<0.001) was found to be significantly higher in patients with IDA. IDA patients with moderate and severe anemia had lower GR activity when compared to IDA patients with mild anemia. But the plasma levels of glucose-6-phosphate dehydrogenase (P<0,600) and 6-phosphogluconate dehydrogenase (P<0,671) did not show any differences between healthy subjects and in patients with IDA. CONCLUSION: It was shown that Glucose-6-Phosphate Dehydrogenase and 6-Phosphogluconate Dehydrogenase have no effect on iron-deficiency anemia in patients. The plasma GR levels of premenopausal women with IDA were found to be higher compared to healthy subjects, which could be secondary to erythrocyte protection against oxidative stress being commonly seen in IDA.

2-Amino-3-cyanopyridine derivatives as carbonic anhydrase inhibitors.

Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous enzymes that catalyze the hydration of CO(2) to bicarbonate and protons. Inhibition of CAs has been clinically exploited for the treatment of various classes of diseases for decades, but investigating new classes of inhibitors continues to be important. We have synthesized a series of 2-amino-3-cyano-4-heteroaryl (5a-l) compounds and characterized the structures by NMR, IR and elemental analyses. We tested the ability of these compounds to inhibit two metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1) isozymes, hCA I and hCA II. Compounds 5d and 5b showed the best inhibition activity against hCA I (IC(50): 33 and 34 µM, respectively), and compound 5d showed the best activity against hCA II (IC(50): 56 µM).

Susceptibility of cord blood antioxidant enzymes glutathione reductase, glutathione peroxidase and glutathione S-transferase to different antibiotics: in vitro approach.

Cord blood has numerous facilities for life and used in many different areas. Cord blood contains many different catalytic proteins including antioxidant enzymes. Here we purified human cord blood glutathione reductase (hcbGR), glutathione S-transferase (hcbGST) and human cord blood glutathione peroxidase (hcbGPx) from human cord blood erythrocytes and analyzed the inhibition effects of the antibiotics incorporating cefuroxime, ceftriaxone, ceftizoxime and cefoperazone, on these enzymes. K(I) values for the drugs ranged from 10.42 to 28.72 µM for hcbGR, 32.7 to 244.8 µM for hcbGPx, and 32.39 to 267.3 µM for hcbGST. Cefuroxime caused the highest inhibition on all enzymes with KI values of 10.42, 32.39, 32.7 µM for hcbGR, hcbGST, and hcbGPx, respectively. All drugs displayed non-competitive inhibition regardless of their structures. Since these drugs are often used during pregnancy, identification of possible undesired impacts on various parameters has a great importance for pharmacological and medical applications.

Effects of some drugs on human cord blood erythrocyte carbonic anhydrases I and II: an in vitro study.

In this [corrected] study, we purified hcbCA I and II from human cord blood erythrocytes using [corrected] Sepharose-4B-l [corrected] tyrosine-sulfanilamide affinity gel chromatography. [corrected]. The inhibition effects of ampicillin sulfate, ceftriaxone, ceftizoxime and ranitidine on hcbCA I and hcbCA II were also monitored. [corrected]. IC(50) values for ceftriaxone, ceftizoxime and ranitidine were found to be 27.l, 79.4 and 55.5 µM, respectively, [corrected] for hcbCA I, and [corrected] 21.0, 79.1 and 66.1 µM, respectively, [corrected] for hcbCA II. [corrected]. According to these results, ampicillin [corrected] sulfate inhibited only hcbCAII and IC(50) value [corrected] of this antibiotic was found to be 56.8 µM. All [corrected] substances were found to be [corrected] non-competitive inhibitors. It is important to study the inhibition effects of these drugs on hcbCA I and II izoenzymes as pregnant women are often prescribed these antibiotics. [corrected]. For this reason, the dosage of [corrected] these drugs should be carefully evaluated [corrected] to minimize side effects.

Effect of Taxifolin on Ischemia/Reperfusion-Induced Oxidative Injury of Sciatic Nerve in Rats.

BACKGROUND: Ischemia is a condition in which blood flow to tissues is decreased or entirely stopped for various reasons. The reperfusion process exacerbates damage caused by ischemia in the organs and tissues. Reactive oxygen species (ROS) are mainly responsible for ischemia-reperfusion (IR) damage. ROS increase results in lipid peroxidation (LPO) and oxidative stress. In the literature, taxifolin reportedly suppresses ROS production. This study aimed to determine the effect of taxifolin, which is a flavonoid, on IR injury of the sciatic nerve in rats. METHODS: This study divided 30 albino Wistar rats into 3 groups: IR without medication (IR) group, taxifolin applied IR (TAX+IR) group, and only dissection made to the sciatic nerve sham group (SHAM). Sciatic nerve injury was induced by applying 2 hours of ischemia and 3 hours of reperfusion to the abdominal aorta and iliolumbar arteries. Biochemical and histopathologic investigations then were performed on sciatic nerve tissues. Malondialdehyde, total glutathione, glutathione reductase, and glutathione peroxidase were analyzed as oxidative stress markers, and tumor necrosis factor-α and interleukin-1ß levels were evaluated as inflammatory stress markers in biochemical tests. RESULTS: The IR group has statistically significantly high oxidant and cytokine levels and low antioxidant levels compared with the TAX+IR group. Taxifolin treatment was also shown to cause significant histopathologic improvement. CONCLUSIONS: We suggest that taxifolin may be effective in preventing IR injury of the sciatic nerve.

Role of neuroepithelial Sonic hedgehog in hypothalamic patterning.

The hypothalamus is a region of the diencephalon with particularly complex patterning. Sonic hedgehog (Shh), encoding a protein with key developmental roles, shows a peculiar and dynamic diencephalic expression pattern. Here, we use transgenic strategies and in vitro experiments to test the hypothesis that Shh expressed in the diencephalic neuroepithelium (neural Shh) coordinates tissue growth and patterning in the hypothalamus. Our results show that neural Shh coordinates anteroposterior and dorsoventral patterning in the hypothalamus and in the diencephalon-telencephalon junction. Neural Shh also coordinates mediolateral hypothalamic patterning, since it is necessary for the lateral hypothalamus to attain proper size and is required for the specification of hypocretin/orexin cells. Finally, neural Shh is necessary to maintain expression of differentiation markers including survival factor Foxb1.

Interactions of melatonin and serotonin with lactoperoxidase enzyme.

Melatonin is the chief secretory product of the pineal gland and is synthesized enzymatically from serotonin. These indoleamine derivatives play an important role in the prevention of oxidative damage. Lactoperoxidase (LPO; EC 1.11.1.7) was purified from bovine milk with three purification steps: Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange, and Sephadex G-100 gel filtration chromatography, respectively. LPO was purified with a yield of 21.6%, a specific activity of 34.0 EU/mg protein, and 14.7-fold purification. To determine the enzyme purity, SDS-PAGE was performed and a single band was observed. The R(z) (A(412)/A(280)) value for LPO was 0.9. The effect of melatonin and serotonin on lactoperoxidase was determined using ABTS as chromogenic substrate. The half-maximal inhibitory concentration (IC(50)) values for melatonin and serotonin were found to be 1.46 and 1.29 µM, respectively. Also, the inhibition constants (K(i)) for melatonin and serotonin were 0.82 ± 0.28 and 0.26 ± 0.04 µM, respectively. Both melatonin and serotonin were found to be competitive inhibitors.

Effects of anakinra on the small intestine mucositis induced by methotrexate in rats.

Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1ß and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.

The inhibitory effect of propofol on bovine lactoperoxidase.

Propofol (2,6-diisopropylphenol) is a hypnotic intravenous agent with in vivo antioxidant properties. This study was undertaken to examine the in vitro effect of propofol on lactoperoxidase (LPO; E.C. 1.11.1.7) obtained from bovine milk. Lactoperoxidase was purified with three purification steps: Amberlite CG-50 resin, CM-Sephadex C-50 ion-exchange chromatography and Sephadex G-100 gel filtration chromatography, respectively. Lactoperoxidase was purified with a yield of 21.6%, a specific activity of 34 EU/mg proteins and 14.7-fold purification. One enzyme unit is defined as the oxidation of 1 micromol ABTS per min under the assay condition (25( degrees )C, pH: 6.0). To determine enzyme purity, sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed and single band was observed. The effect of propofol on lactoperoxidase were determined using 2,2'-azino-bis (3-ethylbenzthiazoline-6 sulfonic acid) diammonium salt (ABTS) as a chromogenic substrate. The IC(50) value of propofol was found as 15.97 microM. Also, K(i) constant for propofol was 3.72 microM and propofol was found as competitive inhibitor.

Effects of some vitamins on lactoperoxidase enzyme activity.

OBJECTIVE: The present paper investigates the in vitro effect of L-ascorbic acid (vitamin C), menadione sodium bisulfate (vitamin K3), and folic acid on purified lactoperoxidase (LPO). METHODS: This enzyme was purified from bovine milk by Amberlite CG 50 resin, CM Sephadex C-50 ion-exchange chromatography, and Sephadex G-100 gel filtration chromatography. RESULTS: Rz (A412/A280) value for the purified LPO was found to be 0.8. Lactoperoxidase was purified 20.45-fold with a yield of 28.8 %. Purity of enzyme was checked by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) method and a single band was observed. All tested vitamins caused inhibition of the enzyme activity and displayed a competitive type of inhibition mechanism. IC(50) values of these three vitamins were 2.03 microM, 0.025 mM, and 0.0925 mM, and the K(i) constants were 0.508+/-0.257 microM, 0.0107+/-0.0044 mM, and 0.0218+/-0.0019 mM respectively. CONCLUSION: The vitamins discussed here displayed inhibition-type competition with LPO enzyme at varying concentrations. Our study showed that L-ascorbic acid exhibited a much higher inhibitory effect at lower concentrations, so it was evidently a more potent inhibitor than other vitamins tested.

The effect of anakinra to nephrotoxicity with cisplatin induced in rats: Biochemical, gene expression and histopathological evaluation.

BACKGROUND: Oxidative stress and interleukin-1 beta (IL-1ß) have been reported to play a role in the pathogenesis of nephrotoxicity induced by cisplatin. OBJECTIVES: The objective of this study was to investigate the effect of anakinra, which is an IL-1ß receptor antagonist, on cisplatin-induced nephrotoxicity in rats, through biochemical, gene expression and histopathological analyses. MATERIAL AND METHODS: The study was designed with 4 groups. For 1 week, the control group (C) and the cisplatin (Cis) group received distilled water, while the cisplatin + anakinra 50 (Cis + ANA50) group and the cisplatin + anakinra 100 (Cis + ANA100) group were intraperitoneally administered 50 mg/kg and 100 mg/kg of anakinra, respectively. The Cis, Cis + ANA50 and Cis + ANA100 groups were intraperitoneally injected with a 2.5 mg/kg dose of cisplatin for 7 days. After sacrifice, the kidney tissue of each rat was extracted for the assessment of the malondialdehyde (MDA) and total glutathione (tGSH) levels, and for gene expression analyses of IL-1ß. The kidney tissues were histopathologically evaluated. Statistical analyses of the data were performed using one-way analysis of variance (ANOVA). RESULTS: The administration of cisplatin (the Cis group) yielded a higher level of MDA (4.75 ±0.25 nmol/mL; p < 0.001) and lower levels of tGSH (1.80 ±0.35 mg/L; p < 0.001) compared to other groups. Cisplatin also increased IL-1ß gene expression (6.33 ±0.27 gene expression levels; p < 0.001) compared to other groups. The impact of anakinra on the MDA and tGSH levels, and on IL-1ß gene expression induced by cisplatin was observed as a reversal of these findings (p < 0.05). Anakinra better prevented an increase of the levels of MDA and IL-1ß at a dose of 100 mg/kg compared to a 50 mg/kg dose. CONCLUSIONS: Anakinra prevents oxidative kidney damage induced by cisplatin, in a dose-dependent manner. This result suggests that anakinra may be useful in the treatment of cisplatin-induced kidney damage.

A novel therapeutics agent: antioxidant effects of hydroxylfasudil on rat kidney and liver tissues in a protamine sulphate-induced cystitis rat model; preliminary results.

Cystitis is defined as an inflammation of the bladder caused by a bacterial infection, and it can be dangerous and painful when it spreads through the internal organs. In this study, antioxidant effects of hydroxylfasudil (HF) at the enzymatic and molecular level on kidney and liver tissues in cystitis rat model, which is caused by inflammation of the rat bladder with a protamine sulphate (PS), was examined. Quantitative changes of reduced glutathione (GSH) and lipid peroxidation (LPO) levels, which are a marker for oxidative stress, were determined in rat kidney and liver tissues for each groups. And then molecular and biochemical impact of HF treatment on antioxidant enzymes including superoxide dismutase (SOD) and catalase (CAT) in cystitis model were studied. The results suggest that HF could be beneficial to the renal and hepatic antioxidant system. Thus, HF might be used as a novel therapeutics agent to eliminate interstitial cystitis.