Abstracts
In this study, xanthine oxidase (XO), malondialdehyde (MDA), myeloperoxidase (MPO) and glutathione (GSH) levels in the ovarian tissues of rats during the development of ischemia and postischemia-induced reperfusion were investigated, and the effect of ATP on ischemia-reperfusion (I/R) damage was biochemically and histopathologically examined. The results of the biochemical analyses demonstrated that ATP significantly reduced the level of XO and MDA and increased the amount of GSH in both ischemia and I/R-applied ovarian tissue at the doses administered. Furthermore, ATP significantly suppressed the increase in MPO activity that occurred following the application of post ischemia reperfusion in the ovarian tissue. The biochemical results obtained in the present study coincide with the histological findings. The severity of the pathological findings, such as dilatation, congestion, haemorrhage, oedema and polymorphonuclear nuclear leukocytes (PMNLs), increased in parallel with the increase observed in the products of XO metabolism. In conclusion, exogenously applied ATP prevented I/R damage by reducing the formation of XO in ischemic ovarian tissue.
xanthine oxidase metabolism; ischemia/reperfusion injury; antioxidant; rat
Neste estudo, a xantina oxidase (XO), o malondialdeído (MDA), mieloperoxidase ( MPO ) e glutationa ( GSH) nos tecidos do ovário de ratos, durante o desenvolvimento de isquemia e reperfusão induzida por pós-isquemia foi investigada, e o efeito de ATP em isquemia e reperfusão (I/R). O dano foi verificado por provas bioquímicas e por histopatologia. Os resultados das análises bioquímicas mostraram que o ATP reduziu significativamente o nível de XO e MDA e aumentou a quantidade de GSH em ambas as isquemia e no tecido do ovário de I / R - aplicado nas doses administradas. Além disso, o ATP suprimiu significativamente o aumento na atividade de MPO que ocorreu na sequência da aplicação de pós-isquemia reperfusão no tecido ovariano. Os resultados bioquímicos obtidos no presente estudo coincidem com os achados histológicos. A gravidade dos achados patológicos, como a dilatação, congestão, hemorragia, edema e polimorfonucleares leucócitos nucleares (PMNLs), aumentou em paralelo com o aumento observado nos produtos do metabolismo XO. Em conclusão, aplicando exogenamente ATP impedido de I/R, houve danos pela redução da formação de tecido de ovário de XO na isquemia.
metabolismo oxidativo da xantina; isquemia/reperfusão; antioxidante; rato
INTRODUCTION
Ischemia is defined as partial or complete oxygen (O2) deprivation in tissues
due to reduced or completely interrupted blood flow. In ischemia, the synthesis of
high-energy phosphates, such as ATP, is decreased in cells due to interruption of the
O2 flow into the tissue (JENNINGS & REIMER, 1991; REITER, 1995REITER, R. J. Oxidative processes and antioxidative defense mechanisms
in the aging brain. The FASEB Journal, Rockville Pike, v.9, p.526-533, 1995.
Available from:
<http://www.fasebj.org/content/9/7/526.abstract>.
http://www.fasebj.org/content/9/7/526.ab...
). The decrease in ATP leads to
inhibition of the Na+, K+ ATPase pump in the cell membrane and an
increase in intracellular Na+ and Ca2+ concentrations (GREEN et al., 1989GREEN, C.J. et al. The importance of iron, calcium and free radicals in
reperfusion injury: an overview of studies in ischaemic rabbit kidneys. Free radical
research communications, Tokyo, v.7, p.255-264, 1989. Available from:
<http://www.ncbi.nlm.nih.gov/pubmed/2684800>.
http://www.ncbi.nlm.nih.gov/pubmed/26848...
). Increased intracellular
Ca2+ concentrations are reported to be cytotoxic (ORRENIUS et al., 1992ORRENIUS, S. et al. Calcium ions and oxidative cell injury. Annals of
Neurology, Wiley-Blackwell, v.32, p.33-42, 1992. Available from:
<http://onlinelibrary.wiley.com/doi/10.1002/ana.410320708/pdf>.
http://onlinelibrary.wiley.com/doi/10.10...
). ATP, adenosine mono-phosphate (AMP),
adenosine, inosine and hypoxanthine are produced from ATP, and ATP utilisation continues
during the ischemia period. Furthermore, xanthine dehydrogenase (XD) is converted to
xanthine oxidase (XO) in this period. In healthy tissues, hypoxanthine is metabolised by
XD, whereas it is metabolised by XO in ischemic tissue (PARKS et al., 1988PARKS, D.A. et al. Conversion of xanthine dehydrogenase to oxidase in
ischemic rat intestine: a reevaluation. American Journal of Physiology, Rockville
Pike, v.254, p.768-774, 1988. Available from:
<http://ajpgi.physiology.org/content/254/5/G768>.
http://ajpgi.physiology.org/content/254/...
). Toxic O2 radicals are not formed in healthy
tissues because nicotinamide dinucleotide is used in the metabolism of hypoxanthine by
XD. Toxic O2 radicals are produced as intermediates in ischemic tissues
because O2 is used in the metabolism of hypoxanthine by XO (GRACE, 1994GRACE, P. A. Ischaemia-reperfusion injury. British Journal of Surgery,
Glasgow, v.81, p.637-647, 1994. Available from:
<http://onlinelibrary.wiley.com/doi/10.1002/bjs.1800810504/full DOI:
10.1002/bjs.1800810504>.
http://onlinelibrary.wiley.com/doi/10.10...
; PARKS
et al., 1988PARKS, D.A. et al. Conversion of xanthine dehydrogenase to oxidase in
ischemic rat intestine: a reevaluation. American Journal of Physiology, Rockville
Pike, v.254, p.768-774, 1988. Available from:
<http://ajpgi.physiology.org/content/254/5/G768>.
http://ajpgi.physiology.org/content/254/...
). Hypoxanthine cannot be metabolised by XO unless reperfusion
occurs in ischemic tissue. As is known, the emptying of cellular energy stores may lead
to cell death in long-lasting ischemia (PARKS et al.,
1988PARKS, D.A. et al. Conversion of xanthine dehydrogenase to oxidase in
ischemic rat intestine: a reevaluation. American Journal of Physiology, Rockville
Pike, v.254, p.768-774, 1988. Available from:
<http://ajpgi.physiology.org/content/254/5/G768>.
http://ajpgi.physiology.org/content/254/...
; ZIMMERMAN & GRANGER, 1992ZIMMERMAN, B.J.; GRANGER, D.N. Reperfusion injury. Surgical Clinics of
North America, Canada, v.72, p.65-83, 1992. Available from:
<http://www.ncbi.nlm.nih.gov/pubmed/1731390>.
http://www.ncbi.nlm.nih.gov/pubmed/17313...
).
Therefore, the intervention in ischemic conditions has always been adequate perfusion of
the tissue. During reperfusion, XO produced during ischemia converts hypoxanthine to
xanthine using locally available O2, leading to excessive free O2
radical production and a decrease in antioxidant defence mechanisms (LINDSAY et al., 1990LINDSAY, T.F. et al. The effect of ischemia/reperfusion on adenine
nucleotide metabolism and xanthine oxidase production in skeletal muscle. Journal of
Vascular Surgery, Chicago, v.12, p.8-15, 1990. Available from:
<http://www.sciencedirect.com/science/article/pii/074152149090360M>.
http://www.sciencedirect.com/science/art...
; LI & JACKSON, 2002LI, C.; JACKSON, R.M. Reactive species mechanisms of cellular
hypoxia-reoxygenation injury. American Journal of Physiology - Cell Physiology,
Rockville Pike, v.282, p.227-241, 2002. Available from:
<http://ajpcell.physiology.org/content/282/2/C227.full-text.pdf+html>.
http://ajpcell.physiology.org/content/28...
). Previous studies showed that XO, the
production of which increases during ischemia due to ATP deficiency, is an essential
component in the mechanism of reperfusion injury. This indicates that ATP administration
may be beneficial for the prevention of ischemia/reperfusion (I/R) injury.
Thus far, no studies have investigated the potentially protective effect of exogenous administration of ATP on I/R-induced ovarian injury in rats. Therefore, the aim of the present study was to investigate the effect of exogenous administration of ATP prior to experimentally induced ischemia and I/R of the rat ovary on biochemical variables and histopathological parameters.
MATERIAL AND METHODS
Animals
A total of 42 female adult Albino Wistar rats weighing between 220-235g were used for the experiment. The rats were obtained from Ataturk University Medical Experiments Research and Training Center (Erzurum, Turkey). The protocols and the procedures were approved by the local Animal Experimentation Ethics Committee (Date: 24. 04. 2012, meeting no: B.30.2.ATA.0.01.02/1845).
Chemical substances
Thiopental sodium was provided by IE Ulagay-Turkey and ATP was supplied by Zdorove Narodu Ukraine.
General procedure
The animals were allocated to 7 groups as Ovarian Ischemia (OI), Ovarian Ischemia/Reperfusion (OIR), 2mg kg-1 ATP + Ovarian Ischemia (AOI-2), 4mg kg-1 ATP + Ovarian Ischemia (AOI-4), 2mg kg-1 ATP+ Ovarian Ischemia/Reperfusion (AOIR-2), 4mg kg-1 ATP+ Ovarian Ischemia/Reperfusion (AOIR-4), and Control Group (Sham Operated- Healthy Control Group (CG). Surgical procedures were performed under sterile conditions in a suitable laboratory environment by administering 25mg kg-1 intraperitoneal (IP) thiopental sodium anesthesia.
Surgical and pharmacological procedures
ATP was injected into AOI-2, AOI-4, AOIR-2 and AOIR-4 groups via the intraperitoneal
route 1h before anaesthesia. A 3h ischemia period was then simulated through vascular
clamping to the lower part of the right ovaries of rats assigned to OI, OIR, AOI-2,
AOI-4, AOIR-2 and AOIR-4 groups. At the end of this period, the ovaries of the rats in
the OI, AOI-2, AOI-4 groups were removed. Reperfusion was provided for 2h by removing
the vascular clamp in the OIR, AOIR-2 and AOIR-4 groups. The ovaries of the rats in the
OIR, AOIR-2 and AOIR-4 groups were removed. Histopathological and biochemical analyses
were performed subsequently in all the samples (KURT et
al., 2013KURT, A. et al. An investigation about the inhibition of acut ischemia /
reperfusion damage by dexmedetomidine in rat ovarian tissue. Gynecological
Endocrinology, London, v.29, p.222-225, 2013. Available from:
<http://informahealthcare.com/doi/abs/10.3109/09513590.2012.665104>.
http://informahealthcare.com/doi/abs/10....
). A 2-2.5cm long vertical incision was made in
the lower abdomen of each rat to reach the ovaries. Ischemia was not performed in the
ovaries of the rats in CG. The ovarian tissue samples were collected from all the
experimental groups, and the assay was conducted simultaneously.
Biochemical procedures
Biochemical analysis of ovarian tissue
The homogenates were prepared to measure the enzymatic activity in the ovarian tissues. The XO, malondialdehyde (MDA), myeloperoxidase (MPO) and total glutathione (tGSH) enzyme activities in the supernatants obtained from these homogenates were determined using established methods reported in the literature.
Determination of xanthine oxidase (XO) activity
The XO activity was measured spectrophotometrically by the formation of uric acid from xanthine through the increase in absorbance at 293nm. In this method, phosphate buffer with EDTA (pH 7.5) is used as the solvent that reaction takes place. A total of 50µl of the sample and 50µl of xanthine (4mM) were added to the phosphate buffer, and then the mixture was incubated for 30min at 37°. A total of 100% (w/v) of TCA was added to stop the reaction mixture. The mixture was centrifuged at 4500g for 20min. The increase in the absorbance of the supernatant was then measured at 293nm (ROWE et al., 1966).
Determination of malondialdehyde (MDA) activity
The concentrations of ovarian lipid peroxidation were determined by estimating MDA
activity using the thiobarbituric acid test (OHKAWA et
al., 1979OHKAWA, H. et al. Assay for lipid peroxides in animal tissues by
thiobarbituric acid reaction. Analytical Biochemistry, Oxford, v.95, p.351-358, 1979.
Available from:
<http://www.sciencedirect.com/science/article/pii/0003269779907383>.
http://www.sciencedirect.com/science/art...
). The rat ovaries were promptly excised and rinsed with cold saline.
The ovarian tissue, weighed and homogenised in 10ml of 100g l-1 KCl. The
homogenate (0.5ml) was added to a solution containing 0.2ml of 80g l-1 sodium
lauryl sulfate, 1.5ml of 200g l-1 acetic acid, 1.5ml of 8g l-1
2-thiobarbiturate and 0.3ml of distilled water. The mixture was incubated at 98°C for
1h. Upon cooling, 5ml of n-butanol:pyridine (15:l) were added. The mixture was vortexed
for 1min and centrifuged for 30min at 4000rpm. The absorbance of the supernatant was
measured at 532nm. The standard curve was obtained by using 1,1,3,3-tetramethoxypropane.
Determination of myeloperoxidase (MPO) activity
The activity of MPO in the total homogenate was measured according to the method of
Wei and Frenkel, with some modifications (WEI &
FRENKEL, 1991WEI, H.; FRENKEL, K. In vivo formation of oxidized DNA bases in tumor
promoter-treated mouse skin. Cancer Research, Philadelphia, v.5, p.4443-4449, 1991.
Available
from:<http://cancerres.aacrjournals.org/content/51/16/4443.long>.
http://cancerres.aacrjournals.org/conten...
). The sample was weighed and homogenised in a 2ml of 50mM
phosphate buffer containing 0.5% hexadexyltrimethyl ammonium bromide (HDTMAB) and
centrifuged at 3500rpm for 60min at 4°C. The MPO activity in the supernatant was
determined using 1,3ml 4-aminoantipyrine-2% phenol (25mM) solution. A total of 25mM
4-aminoantipyrine-2% phenol solution and 0.0005% 1.5ml H2O2 were
added and equilibrated for 3-4min. After establishing the basal rate, 0.2ml of sample
suspension was added and quickly mixed. Increases in the absorbance at 510nm were
recorded at 0.1min intervals for 4min. The absorbance was measured at 412nm using a
spectrophotometer.
Determination of total glutathione (tGSH)
The amount of tGSH in the total homogenate was measured according to the method of
Sedlak and Lindsay with some modifications (SEDLAK &
LINDSAY, 1968SEDLAK, J.; LINDSAY, R.H. Estimation of total, protein-bound, and
nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical
Biochemistry, Oxford, v.25, p.192-205, 1968. Available from:
<http://www.sciencedirect.com/science/article/pii/0003269768900924>.
http://www.sciencedirect.com/science/art...
). The sample was weighed and homogenised in 2ml of 50mM Tris-HCl
buffer containing 20mM of EDTA and 0.2mM of sucrose at pH 7.5. The homogenate was
immediately precipitated with 0.1ml of 25% trichloroacetic acid, and the precipitate was
removed after centrifugation at 4200rpm for 40min at 4°C. The GSH level of the
supernatant was then determined. A total of 1500µl of measurement buffer (200mMTris-HCl
buffer containing 0.2mM of EDTA at pH 7.5), 500µl of supernatant, 100µl of 5,5-dithiobis
(2-nitrobenzoic acid) (DTNB) (10mM) and 7900µl of methanol were added to a tube,
vortexed and incubated for 30min at 37°C. DTNB was used as a chromogen, and it formed a
yellow-coloured complex with SH groups. The absorbance was measured at 412nm using a
spectrophotometer. The standard curve was obtained using reduced glutathione.
Histopathological procedures
The ovaries that were removed from the rats were fixed in 10% formalin solution, sections 4µm in thickness were obtained from the paraffin blocks obtained after the routine tissue follow-up process, and the sections were stained with hematoxylin&eosin (H&E) stain after deparaffinization and rehydration. All the sections were encoded and examined under light microscopy (Olympus CX 51, Tokyo, Japan).
Statistical analysis
All data were subjected to a one-way analysis of variance (ANOVA) using Statistical Package for the Social Sciences (SPSS) 18.0 software. Multiple comparisons were analysed using the Duncan's multiple range test. A P-value 0.05 was considered statistically significant. The results are presented as the mean standard error of mean (SEM).
RESULTS
Biochemical results
As seen in table 1, XO activity in the ovarian tissue of the ischemia-induced OI group was significantly higher than in the OIR group (<0.0001). In addition, the levels of MDA and MPO in the OIR group in which XO activity was lower increased in comparison to the OI group, and the amount of tGSH significantly decreased (P<0.0001). ATP administered in 2 and 4mg kg-1 doses significantly prevented increases in XO, MDA and MPO levels during ischemia and postischemia-induced reperfusion in ovarian tissue and decreases in tGSH. No significant change was observed in the MPO activity of the ischemic ovarian tissue.
Histopathological result
A normal histopathological appearance is observed in figure 1.1.A-B. A moderate dilation, congestion (arrow) and mild hemorrhage (star) were observed in the vessels of the ipsilateral ovarian stroma in the OI group (Figure 1.2A.) compared to a normal histopathological ovary in control group. High magnification assessment provide a better insight in figure 1.2B. In figure 1.3A, vasodilation and congestion (arrow), edema, permanent and severe hemorrhage (star) were observed in the low power field; in Figure. 1.3B, migration and adhesion of a large number of PMNLs (double arrow) to the endothelium were observed in the high power field in the OIR group.
Light microscopy photograph of the ovary in CG. A normal histopathological appearance was observed figure 1.1A High magnification of figure 1.1B. Light microscopy photographs of the ipsilateral ovary in the OI group. A moderate dilation and congestion (arrow) and mild hemorrhage (star) were observed in the vessels of the ovarian stroma figure 1.2A. High magnification of figure 1.2B. Light microscopy photographs of the ipsilateral ovary in the OIR group. In figure 1.3A, vasodilation and congestion (arrow), edema, permanent and severe hemorrhage (star) were observed in the low power field; in 3B, migration and adhesion of a large number of PMNLs (double arrow) to the endothelium were observed in the high power field. Light microscopy photographs of ipsilateral ovaries in the AOI-2 group. A mild congestion (arrow) and mild stromal hemorrhage were observed in figure 1.4A. High magnification of figure 1.4B. In Figure 1.5A light microscopy photographs of the ipsilateral ovaries in the AOI-4 group. High magnification of figure 1.5B. A near-normal histomorphological appearance was observed. In 1.6 light microscopy photographs of the ipsilateral ovaries in the AOIR-2 group. While moderate congestion and dilation (arrow), moderate stromal hemorrhage and edema (star) were observed in the low power field in 6A, migration and adhesion of PMNLs to the endothelium (arrow) were observed in 6B. In figure 1.7A light microscopy photographs of the ipsilateral ovaries in the AOIR-4 group. Mild hemorrhage (arrow) in the ovarian stroma, mild vascular congestion (star) and minimal edema were observed. High magnification of figure 1.7B
A mild congestion (arrow) and mild stromal hemorrhage were observed in figure 1.4A for the AOI-2 group. High magnification assessment provide a better insight in figure 1.4B. In figure 1.5A., a near-normal histomorphological appearance was observed in the AOI-4 group. High magnification assessment provide a better insight in figure 1.5B.In the AOIR-2 group, moderate congestion, dilation (arrow), moderate stromal hemorrhage and edema (star) were observed in the low power field in figure. 1.6A, while migration and adhesion of PMNLs to the endothelium (arrow) were observed in figure. 1.6B. As seen in figure 2.7. mild hemorrhage (arrow) in the ovarian stroma, mild vascular congestion (star) and minimal edema were observed in the AOIR-4 group (Table 2). High magnification assessment provide a better insight in figure 1.7B.
DISCUSSION AND CONCLUSION
This study investigated the effect of ATP on biochemical and histopathological damage
caused by I/R. The results of the biochemical tests demonstrated that XO activity in the
ischemia-induced OI group was 1.6 times higher than in the OIR group. In the literature,
it has been reported that the presence of higher XO activity in ischemic tissue is due
to the conversion of the xanthine dehydrogenase enzyme into XO by a calcium-mediated
protease catalyst in the ischemia mediator (GRACE,
1994GRACE, P. A. Ischaemia-reperfusion injury. British Journal of Surgery,
Glasgow, v.81, p.637-647, 1994. Available from:
<http://onlinelibrary.wiley.com/doi/10.1002/bjs.1800810504/full DOI:
10.1002/bjs.1800810504>.
http://onlinelibrary.wiley.com/doi/10.10...
). In addition, the reduced occurrence of XO activity in the OIR group in
comparison to the OI group could possibly be attributed to the XO activity being
consumed in the production of XO oxidant. ATP used in doses of 2 and 4mg kg-1
in this study significantly decreased XO activity during the formation of ischemia and
postischemia-induced reperfusion in the ovarian tissue. The oxidation of sulfhydryl
groups within XD molecules of cells leads to the formation of XO (HARRISON, 2002HARRISON, R. Structure and function of xanthine oxidoreductase: where
are we now? Free radical biology and medicine, local, v.33, p.774-797, 2002.
Available from:
<http://dx.doi.org/10.1016/S0891-5849(02)00956-5>.
http://dx.doi.org/10.1016/S0891-5849(02)...
). Thus, the decrease in the formation of XO in the
ovarian tissue of the rat groups that received ATP exogenously may be due to antioxidant
activity associated with the generation of ATP. Similarly, the levels of oxidants, such
as MDA and MPO, in the ovarian tissue of the OIR group significantly increased in
comparison to those in the OI group, and their tGSH levels decreased. Paller M.S.
demonstrated that free radicals develop at a low rate during ischemia but that they are
produced in greater numbers when re-oxygenation of the tissue by reperfusion takes place
(PALLER, 1994). Another study also reported that while XO accumulates during the
ischemia period, a large number of toxic radicals are produced by transforming
hypoxanthine into xanthine using the O2 introduced by reperfusion, (CARDEN & GRANGER, 2000CARDEN, D.L.; GRANGER, D.N. Phatophsiology of ischemia-reperfusion
injury. Journal of Pathology, London, v.190, p.255-266, 2000. Available from:
<http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-9896(200002)190:3%3C255::AID-PATH526%3E3.0.CO;2-6/full>.
http://onlinelibrary.wiley.com/doi/10.10...
). In common with these
studies, Ingec et al. reported that the amount of oxidant increased only in
ischemia-induced ovarian tissue and that it was greatly intensified by reperfusion
(INGEC et al. 2011). As is well-known, AMP produced by aerobic tissues in the aerobic
tissues provides the energy required to maintain cell viability by being broken down
into adenosine, inosine and hypoxanthine. In ischemia, the consumption of ATP increases,
and its production decreases (JENNINGS & REIMER, 1991). This event leads to the
depletion of energy stores and the inhibition of the Na+, K+-ATPase pump found in the
cell membrane. ATPase pump inhibition causes an excessive increase in intracellular Na+
and Ca2+ ion concentrations and leads to cell damage (GREEN et al., 1989GREEN, C.J. et al. The importance of iron, calcium and free radicals in
reperfusion injury: an overview of studies in ischaemic rabbit kidneys. Free radical
research communications, Tokyo, v.7, p.255-264, 1989. Available from:
<http://www.ncbi.nlm.nih.gov/pubmed/2684800>.
http://www.ncbi.nlm.nih.gov/pubmed/26848...
). The prevention of ischemia and reperfusion
damage by the administration of ATP in the experiment coincides with the information
reported in the literature.
The use of ATP in doses of 2 and 4mg kg-1 significantly prevented the rise of
MDA and the reduction of tGSH in ischemic ovarian tissue. At the same doses, ATP
significantly suppressed the levels of MDA and MPO, both of which had increased as a
result of reperfusion. Free O2 radicals, which are known to mediate
reperfusion, result in the release of toxic products, such as aldehydes and MDA, from
lipids and stimulate oxidation in the cell membrane (GOULART et al., 2005GOULART, M. et al. Lipoperoxidation products and thiol antioxidants in
chromium exposed workers. Mutagenesis, Oxford, v.20, p.311-315, 2005. Available from:
<http://mutage.oxfordjournals.org/content/20/5/311.full.pdf+html>.
http://mutage.oxfordjournals.org/content...
). MDA, as the final product of lipid peroxidation,
causes severe damage to the cell membrane and its intracellular structures (GOULART et al., 2005GOULART, M. et al. Lipoperoxidation products and thiol antioxidants in
chromium exposed workers. Mutagenesis, Oxford, v.20, p.311-315, 2005. Available from:
<http://mutage.oxfordjournals.org/content/20/5/311.full.pdf+html>.
http://mutage.oxfordjournals.org/content...
). The high level of MPO in
reperfusion could possibly originate from the release of MPO by large numbers of
polymorphonuclear nuclear leukocytes (PMNLs) in the blood entering the ischemic tissue
during reperfusion (ZIMMERMAN & GRANGER,
1992ZIMMERMAN, B.J.; GRANGER, D.N. Reperfusion injury. Surgical Clinics of
North America, Canada, v.72, p.65-83, 1992. Available from:
<http://www.ncbi.nlm.nih.gov/pubmed/1731390>.
http://www.ncbi.nlm.nih.gov/pubmed/17313...
). PNLs convert molecular O2 into superoxide and hydrogen
peroxide. The hydrogen peroxide in the chloride ions is reduced to hypochlorous acid, a
toxic and strong oxidant, via the MPO enzyme found in the azurophilic granules of
neutrophils (ZIMMERMAN & GRANGER, 1992ZIMMERMAN, B.J.; GRANGER, D.N. Reperfusion injury. Surgical Clinics of
North America, Canada, v.72, p.65-83, 1992. Available from:
<http://www.ncbi.nlm.nih.gov/pubmed/1731390>.
http://www.ncbi.nlm.nih.gov/pubmed/17313...
).
Studies have experimentally demonstrated that postischemia reperfusion leads to severe
damage of other tissues, as well as the ovaries (BOREKCI
et al., 2009BOREKCI, B. et al. The protective effect of dehydroepiandrosterone on
ovarian tissues after torsion-detorsion ınjury: a stereological and histopathological
study. Eurasian Journal of Medicine, Erzurum, v.41, p.22-27, 2009. Available from:
<http://www.eajm.org/sayilar/180/buyuk/pdf_EAJM_154.pdf.>.
http://www.eajm.org/sayilar/180/buyuk/pd...
; COSKUN et al., 2011; TOK et al.,
2012TOK, A. et al. Effect of mirtazapine on oxidative stress created in rat
kidneys by ischemia-reperfusion. Renal Failure, London, v.34, p.103-110, 2012.
Available from:
<http://informahealthcare.com/doi/abs/10.3109/0886022X.2011.623499>.
http://informahealthcare.com/doi/abs/10....
). Moreover, previous studies reported that levels of ATP and
Na+-K+-ATPase are decreased in ischemic tissue (GABRYEL
et al., 2012GABRYEL, B. et al. Neuronal autophagy in cerebral ischemia--a potential
target for neuroprotective strategies? Pharmacological Reports, Poland, v.64, p.1-15,
2012. Available from:
<http://www.if-pan.krakow.pl/pjp/pdf/2012/1_1.pdf>.
http://www.if-pan.krakow.pl/pjp/pdf/2012...
; SINGH et al., 2012). The biochemical results obtained in the
present study coincide with the histopathological findings. In addition, the severity of
the pathological findings, such as dilatation, congestion, haemorrhage, oedema and PNLs,
increased in parallel with the rise in XO metabolism products. In conclusion,
exogenously administered ATP prevented the increase of XO, MDA and MPO, all of which are
known to be oxidant parameters in ovarian tissue in ischemia and postischemia-induced
reperfusion. These results suggest that the use of ATP at the clinic would be helpful as
a preventive agent of both ovarian ischemia and post ischemia reperfusion damage.
ACKNOWLEDGEMENTS
Authors do not have financial support.
REFERENCES
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Publication Dates
-
Publication in this collection
July 2014
History
-
Received
29 July 2013 -
Accepted
10 Jan 2014