N-acetylcysteine ameliorates 5-fluorouracil-induced ovarian injury in rats

Objective: Although 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutics worldwide, it has been shown that 5-FU administration can cause reproductive toxicity in recent years. N-acetylcysteine (NAC) is the precursor of glutathione, the most important endogenous antioxidant molecule and is known for its effective antioxidant and anti-inflammatory properties. Although NAC is one of the most studied antioxidant molecules, its curative effect against ovarian damage caused by 5-FU has not been demonstrated to date. It was therefore aimed to investigate whether NAC is therapeutic against 5-FU-induced ovotoxicity in this study for the first time.Methods: Rats were first exposed to a single dose of 5-FU (100 mg/kg) and then treated with NAC (10 and 20 mg/kg) for three days. The oxidative stress, inflammation and apoptosis markers in ovarian tissues were also determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically.Results: It was revealed that the levels of oxidative stress, inflammation and apoptosis biomarkers in ovarian tissue increased by 5-FU administration (p<.005). Treatments with NAC significantly restored these damages dose-dependently (p<.005). Moreover, these biochemical findings were confirmed by histological examination.Conclusion: NAC can be considered as a potential therapeutic molecule against 5-FU-induced reproductive toxicity, as it can abolish the ovarian toxicity caused by 5-FU by reducing oxidative stress, inflammation and apoptosis

Homosistein, vitamin B12 and folic acid levels in patients with pediatric celiac disease

Giriş: Bu çalışmada amacımız çölyak hastalarında malabsorbsiyon nedeni ile gastrointestinal sistemden vitamin B12 ve folik asit emilimlerinin bozulmasının serum homosistein düzeyleri üzerine etkisini araştırmak. Gereç ve Yöntem: Yaşları 2-17 arasında değişmekte olan 32 tedavi öncesi çölyak hastası, 14 tedavi sonrası çölyak olgusu ve 30 sağlıklı kontrolde homosistein düzeyleri araştırıldı. Tedavi öncesi ve tedavi sonrası hasta grubunda ayrıca plazma vitamin B12 ve folik asit düzeyleri bakıldı. Bulgular: Homosistein için aritmetik ortalama±SD; tedavi öncesi hasta grubunda 22,87±1,69 µmol/L, tedavi sonrası hasta grubunda 17,31±1,94 µmol/L ve kontrol grubunda 15,21±1,69 µmol /L olarak belirlendi. Folik asit için ortalama±SD; tedavi öncesi hasta grubunda 7,04±0,74 ng/ml, tedavi sonrası hasta grubunda 12,95±1,9 ng/ml olarak bulundu. Folik asit ve homosistein için tedavi öncesi hasta grubu ile tedavi sonrası hasta grubu arasındaki fark istatistiksel olarak anlamlı bulundu (p0,05). Sonuç: Araştırmamızda tedavi öncesi çölyak hastalarında homosistein düzeyleri tedavi sonrası ve kontrol grubundan yüksek bulundu. Bu çalışmada gruplar arasında folik asit düzeyleri açısından anlamlı fark bulunması, folik asit düzeylerinin homosistein konsantrasyonlarındaki artışla daha fazla ilişkili olabileceğini göstermektedir.Introduction: Our aim in this study was to investigate effects of vitamin B12 and folic acid malabsorption to homocysteine levels in celiac patients. Materials and Methods: Between 2-17 years of ages 32 celiac patients before treatment, 14 celiac patient in remission and 30 healthy controls involved in this study. Homocystein levels were evaluated in all groups. In addition plasma levels of vitamin B12 and folic acid determined in celiac and remission groups. Results: Homocysteine levels as arithmetic mean±SD found 22.8±1.69 µmol/L in celiac group, 17.31±1.94 µmol/L in remission group and 15.21±1.69 µmol/L in control group. Folic acid levels as arithmetic mean±SD found 7.04±0.74 ng/ ml in celiac patients and 12.95±1.9 ng/ml in remission group. There is statistically significant difference between folic acid and homocysteine levels of two groups (p0.05). Conclusions: In our study homocysteine levels were found to be higher in celiac group than remission group. In this study, difference in folic acid levels between two groups may show that changes in folic acid levels related to changes in homocysteine levels

Low dose dopamine prevents end organ damage in experimentally induced pancreatitis

Background/Aims: End organ damage due to microcirculatory failure plays an important role in the pathogenesis of acute pancreatitis (AP). The aim of this study was to investigate whether dopamine, a vasoactive agent, is beneficial in the prevention of local and systemic injury in acute pancreatitis. Methodology: Pancreatitis was induced in rats with 5% Na-taurocolic acid infusion into the pancreatic duct. Rats were resuscitated for four hours with saline in the pancreatitis group (P), lactated ringer's (LR) solution in the LR group and low dose dopamine (5 mu g/kg/min) + LR in the D-LR group. The sham group (S) underwent pancreatic duct cannulation only. Rectal temperature (RT) and mean arterial pressure (MAP) were monitored throughout the experiment. Blood samples for amylase, lipase, WBC and blood gas analysis were taken at baseline and at the end of the study. All rats were sacrificed at the 4th hour and pancreatic and lung tissues were removed for histopathological examination and tissue myeloperoxidase (MPO) activity. Results: MAP was lower in the P and LR groups than the sham and the D-LR groups. RT was higher in P and LR groups than the sham and the D-LR groups. Base deficit was higher in the P group than the sham and the D-LR groups. The lung MPO activity was higher in the P group than all the others. Lung MPO activity that is closest to the sham was that of D-LR group's. The pancreatic MPO activity was found to be increased in the P and decreased in the LR groups. Conclusions: In this experimental model for AP, low dose dopamine + LR resuscitation attenuates the lung injury but not the local pancreatic injury

Continuous 900-megahertz electromagnetic field applied in middle and late-adolescence causes qualitative and quantitative changes in the ovarian morphology, tissue and blood biochemistry of the rat

Demir, Selim/0000-0002-1863-6280WOS: 000427080600010PubMed: 29268055Purpose: The purpose of this study was to use histological and biochemical methods in order to evaluate changes taking place in the ovarian of rats exposed to the effect of a 900-megahertz (MHz) electromagnetic field (EMF) in middle and late adolescence. Materials and methods: Twenty-four 34-d-old female Sprague-Dawley rats were assigned equally to control, sham and EMF groups. EMF group rats were exposed to the effect of a 900-MHz EMF for 1 h a day, at the same time every day between postnatal days 35 and 59, while inside an EMF cage. Sham group rats were kept inside the EMF cage for the same time between postnatal days 35 and 59 without being exposed to any EMF effect. At the end of the study, rats' ovarian were removed and blood specimens were taken. Right ovarium tissues were subjected to routine histological procedures and stained with hematoxylin and eosin, periodic acid shift and Masson's trichrome. Follicles were counted in ovarian sections stained with hematoxylin and eosin. The TUNEL method was used to evaluate apoptosis. Left ovarian tissue and blood specimens were investigated biochemically. Results: Histopathological examination of EMF group ovarian tissue revealed thinning in the zona granulosa and theca layers, shrinking in granulosa cells, reduced mitotic activity and leukocyte infiltration in the follicles and stroma. Secondary follicle numbers in the EMF group were significantly lower than in the other groups. In terms of biochemistry, EMF and sham group superoxide dismutase, catalase and anti-Mullerian hormone levels and EMF group 3-nitrotyrosine values increased significantly compared to the control group. EMF and sham group serum catalase and 8-hydroxy-deoxiguanosine values increased significantly compared to the control group, and EMF group total oxidant status and oxidative stress index values were significantly higher compared to the sham and control groups. Conclusions: A total of 900-MHz EMF applied in middle and late adolescence may cause changes in the morphology and biochemistry of the rat ovarium.Karadeniz Technical University Research Fund [TTU-2015-5240]This research was supported by the Karadeniz Technical University Research Fund, Project number TTU-2015-5240

Effects of prenatal exposure to a 900 MHz electromagnetic field on 60-day-old rat testis and epididymal sperm quality

WOS: 000377636600002PubMed: 26472053We investigated the effects of exposure in utero to a 900 megahertz (MHz) electromagnetic field (EMF) on 60-day-old rat testis and epididymis. Pregnant rats were divided into control (CG; no treatment) and EMF (EMFG) groups. The EMFG was exposed to 900 MHz EMF for 1 h each day during days 13 - 21 of pregnancy. Newborn rats were either newborn CG (NCG) or newborn EMF groups (NEMFG). On postnatal day 60, a testis and epididymis were removed from each animal. Epididymal semen quality, and lipid and DNA oxidation levels, apoptotic index and histopathological damage to the testis were compared. We found a higher apoptotic index, greater DNA oxidation levels and lower sperm motility and vitality in the NEMFG compared to controls. Immature germ cells in the seminiferous tubule lumen, and altered seminiferous tubule epithelium and seminiferous tubule structure also were observed in hematoxylin and eosin stained sections of NEMFG testis. Nuclear changes that indicated apoptosis were identified in TUNEL stained sections and large numbers of apoptotic cells were observed in most of the seminiferous tubule epithelium in the NEMFG. Sixty-day-old rat testes exposed to 900 MHz EMF exhibited altered sperm quality and biochemical characteristics

The effect of prenatal exposure to 900-MHz electromagnetic field on the 21-old-day rat testicle

Demir, Selim/0000-0002-1863-6280WOS: 000327569100022PubMed: 24095929The aim of this study was to investigate the effect of exposure to a 900-MHz electromagnetic field (EMF) in the prenatal term on the 21-old-day rat testicle. Pregnant rats were divided into control (CG) and EMF (EMFG) groups. EMFG was exposed to 900-MHz EMF during days 13-21 of pregnancy. Newborn CG rats were obtained from the CG and newborn EMFG (NEMFG) rats from the EMFG. Testicles were extracted at postnatal day 21. Lipid peroxidation and DNA oxidation levels, apoptotic index and histopathological damage scores were compared. NEMFG rats exhibited irregularities in seminiferous tubule basal membrane and epithelium, immature germ cells in the lumen, and a decreased diameter in seminiferous tubules and thickness of epithelium. Apoptotic index, lipid peroxidation and DNA oxidation were higher in NEMFG rats than in NCG. 21-day-old rat testicles exposed to 900-MHz EMF in the prenatal term may be adversely affected, and this effect persists after birth. Published by Elsevier Inc

Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway

Although cisplatin (CDDP) is an effective anticancer agent, the ovotoxicity that can occur in female patients limits its use. Oxidative stress (OS) and inflammation are known to contribute to CDDP-induced ovotoxicity. Vanillic acid (VA) is a dietary herbal secondary metabolite with high free radical scavenging activity. It was aimed to evaluate the therapeutic effects of VA against CDDP-induced ovotoxicity in rats in this study for the first time. Ovotoxicity was achieved with a single dose of CDDP (5 mg/kg) in female rats. The therapeutic effect of VA was evaluated with 3-day administration of two different doses (5 and 10 mg/kg). While OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were measured in tissue samples, the levels of reproductive hormones were determined in serum samples using colorimetric methods. The results showed that CDDP-induced nuclear factor erythroid 2-associated factor 2 (Nrf2) inhibition combined with increased OS, inflammation, ERS and apoptosis increased ovarian damage. VA treatments reversed these changes via activating Nrf2 pathway dose-dependently. In addition, histopathological findings also supported the biochemical results. VA may be a good therapeutic molecule candidate for CDDP-induced ovarian damage due to strong antioxidant and Nrf2 activator properties

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENT What is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential. What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential. What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity

Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue

Synthesis, in vitro DNA interactions, cytotoxicities, antioxidative activities, and topoisomerase inhibition potentials of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes with azo-oxime ligands

Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) transition metal complexes of 2-hydroxy-5-[(E)-(4-phenyl) diazenyl] benzaldehyde oxime and 2-hydroxy-5-[(E)-(4-nitrophenyl) diazenyl] benzaldehyde oxime ligands were synthesized and characterized through NMR, IR, ESI mass, and UV analysis. DNA binding abilities of the complexes were revealed using a UV-Vis spectrophotometer with the absorption titration and competitive binding techniques. Hydrolytic and oxidative DNA cleavage activities under different conditions were also proved. Topoisomerase I inhibition efficiencies and in vitro free radical scavenging activities of all complexes were examined. Finally, the selective cytotoxic potentials of all complexes were evaluated in human colon cancer, normal colon, and fibroblast cell lines using the water-soluble tetrazolium salt (WST-1) assay. The complexes had the ability to intercalate into stacked base pairs of DNA and topoisomerase I activity was reasonably inhibited in their presence in 0.4 mM concentrations. The abilities for scavenging of DPPH and hydroxyl radicals were found to be higher than those of known standard antioxidants (ascorbic acid, butylated hydroxyanisole, and mannitol). The results obtained from the cytotoxicity experiments are especially promising for further research, which must be carried out for the evaluation of the studied complexes as anticancer drugs