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Abstract

Reactive oxygen species (ROS), also known as free radicals, are generated during cellular respiration. Under normal conditions, the body has the ability to neutralize the effects of free radicals by using its antioxidant defenses. In the case of an imbalance between oxidants and antioxidants, free radical production exceeds the capacity of organic combustion, resulting in oxidative stress. Of all the cellular components compromised by the harmful effects of ROS, the cell membrane is the most severely affected owing to lipid peroxidation, which invariably leads to changes in the membrane structure and permeability. With lipid peroxidation of the cell membrane, some by-products can be detected and measured in tissues, blood, and other bodily fluids. The measurement of biomarkers of oxidative stress is commonly used to quantify lipid peroxidation of the cell membrane in humans, a species in which ROS can be considered as a cause or consequence of oxidative stress-related diseases. In dogs, few studies have demonstrated this correlation. The present review aims to identify current literature knowledge relating to oxidative stress diseases and their detection in dogs.
1431
Semina: Ciências Agrárias, Londrina, v. 37, n. 3, p. 1431-1440, maio/jun. 2016
Recebido para publicação 18/11/14 Aprovado em 02/10/15
DOI: 10.5433/1679-0359.2016v37n3p1431
Oxidative stress in dogs
Estresse oxidativo em cães
Claudia Russo1*; Ana Paula Frederico Rodrigues Loureiro Bracarense2
Abstract
Reactive oxygen species (ROS), also known as free radicals, are generated during cellular respiration.

its antioxidant defenses. In the case of an imbalance between oxidants and antioxidants, free radical
production exceeds the capacity of organic combustion, resulting in oxidative stress. Of all the cellular
              
             
and permeability. With lipid peroxidation of the cell membrane, some by-products can be detected

stress is commonly used to quantify lipid peroxidation of the cell membrane in humans, a species in
which ROS can be considered as a cause or consequence of oxidative stress-related diseases. In dogs,
  
knowledge relating to oxidative stress diseases and their detection in dogs.
Key words: Oxidative stress. Lipid peroxidation. Free radicals. Dogs.
Resumo
Nos processos decorrentes da respiração celular, são gerados produtos denominados espécimes reativos
de oxigênio (EROS), conhecidos também como radicais livres. Em condições normais, o organismo
possui capacidade de neutralizar os efeitos dos radicais livres utilizando suas defesas antioxidantes. Em
situações de desequilíbrio entre agentes oxidantes e antioxidantes, a produção de radicais livres excede
a capacidade orgânica de neutralização, resultando na condição conhecida como estresse oxidativo.
Dentre todos os componentes celulares atingidos pelos efeitos nocivos dos EROS, as membranas
celulares são as estruturas mais severamente acometidas, devido à peroxidação lipídica, que leva,
invariavelmente, a alterações estruturais e também na sua permeabilidade. Na peroxidação lipídica da
membrana celular, alguns subprodutos podem ser detectados e mensurados nos tecidos, sangue e outros

          
consideradas como causa ou consequência de doenças relacionadas ao estresse oxidativo. Nos cães,
alguns poucos estudos demonstram essa correlação. A presente revisão tem como principal objetivo

às doenças em cães bem como as possíveis formas de detecção de biomarcadores na espécie canina.
Palavras-chave: Estresse oxidativo. Lipoperoxidação. Radicais livres. Cães.
1 
Brasil. E-mail: russo.claudia@hotmail.com
2 Profª Drª Associada, Departamento de Medicina Veterinária Preventiva, UEL, Londrina, PR. E-mail: anapaula@uel.br
* Autor para correspondência
REVISÕES/REVIEWS
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Semina: Ciências Agrárias, Londrina, v. 37, n. 3, p. 1431-1440, maio/jun. 2016
Russo, C. ; Bracarense, A. P. F. R. L.
Introduction

on tissues and cells have been a leading topic in a

over 40 years (SALVADOR; HENRIQUES, 2004).
More recently, this subject has been gaining ground

for conducting research on the correlation of
oxidative stress to diseases. Free radical production

body (ARAUJO et al., 2010), the use of antioxidants,
      

  
of this review is to provide the veterinarian with an
overview of the topic, addressing dogs in particular.
Development
During cellular respiration, oxygen, the key
element required to produce energy for the cellular
metabolism and oxidation of organic compounds,
is consumed and reduced, generating a series
of highly reactive chemical substances called
reactive oxygen species (ROS), also known as
free radicals (DALLAQUA; DAMASCENO,
     
a highly reactive molecule or atom, having one or
more unpaired electron in the last electron layer.
At high concentrations, ROS can interact with
the biomolecules that are present in tissues, cell
membranes, and organelles, causing cell injury
(VALKO et al., 2007). Under normal conditions,
        
the free radicals by using its antioxidant defenses.
However, in situations of imbalance between
oxidant and antioxidant agents, the production of
free radicals exceeds the neutralizing capacity of
organic compounds, resulting in oxidative stress

Of all the cellular components compromised by


which invariably leads to alterations in the
membrane structure and permeability (FERREIRA;
     
generated during oxidative stress is questionable
owing to their very low concentrations and the high
speed at which they react with other biomolecules.


ROS; that is, in the measurement of its by-products

During lipid peroxidation of cell membranes,
certain by-products can be detected and measured
      
Determination of malondialdehyde (MDA) in
the serum is commonly used to quantify the lipid
peroxidation of cell membranes in living organisms,
where the ROS are seen as a cause or consequence
of diseases related to oxidative stress (FERREIRA;

Human medical research has been studying

on the living organism for many years. Studies in
     
Initially, emphasis was given to understanding the

that the energy released by this type of radiation
leads to changes in the orbits of electrons, making
the atoms, especially oxygen, highly reactive,
leading to the formation of molecules such as
molecular oxygen and hydrogen peroxide (H2O2),
which are considered free radicals (SALVADOR;
HENRIQUES, 2004). Currently, the association
between oxidative stress and diseases such
as cancer,
  
autoimmune disorders, in addition to aging-related
processes, is well established (HALLIWELL;
   

animals of interest to veterinary medicine, studies
on these associations are recent and still scarce

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Oxidative stress in dogs
Reactive oxygen species
It can be said that ROS are present in all
biological systems. During aerobic cellular
metabolism under physiological conditions, oxygen
undergoes tetravalent reduction by accepting four
electrons, which results in the formation of water
(H2O) and other reactive intermediate compounds,
such as the radicals superoxide (O2
-), hydroxyl
(•OH), and H2O2   2
- occurs in
almost all aerobic cells and is produced during the
activation of neutrophils, monocytes, eosinophils,
and macrophages. Although it is considered to be
only mildly reactive, some secondary biological
lesions have been observed in systems that generate
O2
- 
     
2
-,
since it demonstrates the ability to easily induce
damage in biological membranes (HALLIWELL;
     
considered to be the most reactive of all ROS
in biological systems. It can rapidly combine
with other radicals or metals at the site where it
was produced, leading to DNA deactivation or
mutations, inactivation of proteins, and oxidation
of fatty acids in cell membranes (HALLIWELL;
   2O2 is not
considered a free radical per se, it is very harmful
because it does not have an unpaired electron.

production of •OH, which is highly toxic to the
cell. In addition to having a long half-life, H2O2
is capable of crossing lipid layers and binding to
proteins bound to iron, as occurs in erythrocytes,
and therefore its toxicity increases in the presence

Elements such as metals (particularly iron,
which exists in abundance in the body) have been
     
use of iron chelating agents has been indicated for
certain diseases, such as head trauma in humans

nitrogen (reactive nitrogen species (RNS)), sulfur,
copper, and manganese may also be considered
free radicals in biological systems and can be
associated with cell damage through oxidative
stress (VASCONCELOS et al., 2007).
Biomarkers of oxidative stress

biomolecules is the formation of substances that can
be used as markers of oxidative damage. Currently,
numerous studies are being conducted to validate
       
uncertainty over which of the available biomarker
detection methods is the most accurate, or the more

      
      

humans, genetic, nutritional, environmental, and
even cultural factors may change the redox balance
(balance between oxidizing reactive species and the
antioxidant system) of a population (KADIISKA et

Despite this fact, some biomarkers are
     
can be detected directly through electron
paramagnetic resonance, but the cost and technical
requirements hamper its routine use (FERREIRA;

used nowadays detect the action of ROS indirectly,
either by measuring the products generated from
its action on biomolecules or by measuring the
quality and quantity of antioxidants, thereby

commonly used are the spectrophotometric and
chromatographic methods that measure the activity
of antioxidant enzymes, such as superoxide

peroxidase. SOD catalyzes the dismutation of
O2
- to H2O2     2O2 to
H2O and O2; and glutathione peroxidase acts on

components of the enzymatic antioxidant system.
1434
Semina: Ciências Agrárias, Londrina, v. 37, n. 3, p. 1431-1440, maio/jun. 2016
Russo, C. ; Bracarense, A. P. F. R. L.
A series of non-enzymatic substances are also
part of the antioxidant system. In the extracellular
medium (serum and plasma), several non-enzymatic
antioxidant agents (e.g., vitamin C, vitamin E, and

idea of measuring antioxidant substances as a way
to assess the presence of oxidative damage, using

considers the cumulative action of all antioxidants
present. Other authors suggest that this method
          
necessarily desirable, as the antioxidant enzymes
are not always decreased in disease conditions

of the presence of oxidative stress can be performed
through measurement of biomarkers for the damage
caused by ROS, RNS, and other radicals, such
as MDA, isoprostanes, lipoperoxides, and other
derivatives of lipid peroxidation of cell membranes.
MDA is currently regarded as a general
biomarker
of oxidative damage in the plasma
       

biological systems is an important parameter for the
assessment of cellular oxidative stress (PILZ et al.,


cytotoxic and genotoxic, and should be considered
more than just a biomarker of oxidative damage,
owing to its interaction with DNA and other
proteins. High levels of MDA are routinely used as
a way to detect oxidative stress in several human
diseases, such as systemic lupus erythematosus,
diabetes, pulmonary diseases, Alzheimer’s disease,
and cancer, which allow us to have funding for the
   
     
       
measuring MDA is the thiobarbituric acid reactive
    
    
reactive to barbituric acid, among which MDA is
the main component. However, the technique has
    
      


Nowadays, other biomarkers of lipid
peroxidation, such as isoprostanes and acrolein,
are also considered as important for determining
oxidative damage in humans and, more recently, in
animals (LIMA; ABDALLA, 2001; MARQUIS et

Oxidative stress and related diseases
    
showing that many diseases are related to the

       
or RNA of the cell. When a break occurs in the
DNA strand, it can reconnect in another position,
      
of the processes causing mutation, which can be
related to oncogenesis. Likewise, changing the
sequence of the amino acids of a protein that act
as an enzyme can lead to a loss of or change in its

     
the active and passive transport systems and can
lead to rupture of the membrane and subsequent
cell death. When lipid peroxidation occurs
in the blood, it aggravates the vessel walls,
favoring the accumulation of lipids, which can
trigger atherosclerosis, stroke, infarction, or


of neoplasms in humans in search for information
on the behaviors of ROS and their relationship with
diseases. In a study comparing the intestinal mucosa
of healthy individuals with those of colorectal cancer
patients, the levels of oxidative damage to the DNA

with the neoplasm. Interestingly, the normal
tissue also had some level of oxidative damage,
demonstrating the importance of ROS in the initial
1435
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Oxidative stress in dogs
aggression to the intestinal mucosa (RIBEIRO et
al., 2007). Another study demonstrated the presence
of oxidative stress in women with breast cancer
  

serum MDA levels were also higher than those of
the control group (SENER et al., 2007).
In veterinary oncology, oxidative stress in canine
lymphoma is also detected via MDA and isoprostane
     
the concentrations of antioxidants agents such as
     
   

with multicentric lymphoma (MACEDO, 2010). In
another study, dogs with multicentric lymphoma
     
presence of anemia and oxidative stress, detected
 

Recently, a study compared the levels of MDA
between a group of 101 healthy dogs and a group


suggesting that these animals were under oxidative

serum MDA concentration was determined by the
       
the serum of substances reactive to barbituric acid,
where the MDA is the main component. Several
studies have also indicated the relationship between
oxidative stress and the development of mammary
tumors in dogs, mainly by correlating serum and

well as the levels of antioxidants such as vitamin E and
vitamin C (SZCZUBIAL et al., 2004; FRANCISCO



of MDA and nitric oxide (NO) and decreased serum
concentrations of vitamin C (considered to be the
        
malignant breast neoplasms. According to this
author, in addition to the oxidative stress detected,
the decrease of antioxidant defenses such as vitamin
C could be related to carcinogenesis.
     
considered antioxidant and cytoprotective was
evaluated in cultured canine aortic endothelial
cells, submitted to the oxidative action of H2O2
(RIPOLL et al., 2012). In that study, the authors
     
and -carnitine, both antioxidant agents already
in use for the treatment of canine cardiopathies,
     
extract. Since the presence of oxidative stress in
canine cardiopathies has already been established


capacity like the ones studied above, so that they can
be included and prescribed as part of the treatment
of canine heart diseases. In veterinary medicine,
oxidative stress has also been linked with kidney
     
healthy dogs and dogs with prerenal azotemia was
compared, showing that the diseased dogs had a
lower antioxidant capacity. Moreover, in these
animals, there was an acceleration of neutrophil
     

other hand, oxidative metabolism should occur in
a physiological manner and is part of the immune
response against antigens. For example, after the
phagocytosis of microorganisms, it is expected
that normal neutrophils will lead the microbial
cells to death via the action of lysosomal enzymes
and oxidizing agents. An ex vivo study showed
that neutrophils from healthy dogs, exposed to the
 

metabolism, due to changes in O2
- production,

was similar to what occurs in humans with chronic
kidney failure, a situation in which the inhibition of
ROS production is harmful to the body (BARBOSA
et al., 2010).
1436
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Russo, C. ; Bracarense, A. P. F. R. L.
     
ischemia-reperfusion injury has been extensively
      
  

of substances with antioxidant potential that can
be included in therapeutic procedures. Natural
substances containing phenolic derivatives, such
     
inhibiting the action of free radicals, preventing lipid
peroxidation, and therefore improving endothelial
and neuroprotective functions (MENDES, 2012).
It should also be mentioned here that a recent
study observed an increase in the concentrations
of isoprostanes and acrolein in the spinal cord of

the nerve degeneration was due to oxidative stress,
similar to what occurs in humans with recurrent
neurodegeneration of the spinal cord after injury

Other infections, including cutaneous conditions
such as demodicosis, can also be related to
oxidative stress (ROMANUCCI et al., 2011).
According to authors who observed decreased
levels of endogenous antioxidants (e.g., glutathione
       
localized and generalized demodicosis, the disease
is related to the occurrence of oxidative stress,
suggesting supplementation with antioxidants as
         
study, the presence of oxidative stress in the eyeball
     
was compared between a group with intraocular
lens implant and a group without lens implant. It
was found through quantitative determination of
proteins in the aqueous humor and evaluation of total
antioxidant activity (also in the aqueous humor) that
the presence of the implanted lens contributed to
the occurrence of oxidative stress in the intraocular

      
have sought to relate oxidative stress with fertility,
by identifying and quantifying the antioxidant
substances in the seminal plasma of fertile and
sub-fertile dogs, in addition to analyzing the
     
diet with antioxidants (ANDRADE et al., 2010;
LOPES et al., 2011). Another study, also in the
     
activity and serum concentrations of biomarkers
of oxidative damage in dogs subjected to an
    
      
     
even after several days post-operation, suggesting
that these dogs would be more susceptible to
diseases related to oxidative stress (SZCZUBIAL

Nonpathological conditions in which oxidative
stress can occur should also be considered. A

glutathione peroxidase enzyme was observed
in dogs submitted to intense exercise for a short
period of time (POLIZEL, 2011). In that study, the
increased levels of glutathione peroxidase were
related to an increased production of free radicals, a

by the body during physical exertion.
Conclusion
     
stress or even of antioxidant substances in the
        
studies that show the relationship between free
radicals and diseases, either as a cause, or as an
    
of the use of antioxidants as adjuvant treatment
that aims to minimize oxidative damage can also
be studied in canine medicine. Studies that seek to

of parameters that can be used as references in
       
      
to basic research and to therapeutic targeting in the
routine clinical setting.
1437
Semina: Ciências Agrárias, Londrina, v. 37, n. 3, p. 1431-1440, maio/jun. 2016
Oxidative stress in dogs
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        
      
        
   
      

  
       

        
        
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Oxidative stress in dogs
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       
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Russo, C. ; Bracarense, A. P. F. R. L.
... This aligns with Panda et al. (2009), who reported a significant increase in lipid peroxide levels. Russo & Bracarense (2016) stated that the measurement of oxidative stress biomarkers is used to determine the level of lipid peroxidation of the cell membrane. MDA is a product of lipid peroxidation of cell membranes and is one of the general biomarkers of oxidative damage (Sim et al., 2003;Kadiiska et al., 2005). ...
... MDA is a product of lipid peroxidation of cell membranes and is one of the general biomarkers of oxidative damage (Sim et al., 2003;Kadiiska et al., 2005). According to Del Rio et al. (2005) and Russo & Bracarense (2016), MDA is both genotoxic and cytotoxic and has deleterious interaction with DNA and proteins of the host. The presence of many prognosticators has made detections of patients at high risk of death and their subsequent planned management more encouraging and successful (Schoeman et al., 2013). ...
Article
Full-text available
Canine parvovirus is a deadly virus affecting the Canid family, causing virus-induced destruction of rapidly dividing haemopoietic precursor cells such as crypts of intestinal epithelial cells, thymus, lymph nodes, bone marrow precursor cells, blood cells and cardiac cells leading to multi-organ dysfunctions. The aim of this study was to determine the haematological, serum biochemical and electrolytic changes associated with canine parvovirus (CPV) -2 infection. An immunochromatographic test was used to differentiate the virus-positive and negative dogs using faecal samples. One hundred and sixty whole blood and serum samples were collected from apparently healthy and CPV-2-positive dogs in Plateau State, Nigeria. Haematological, serum biochemical and electrolytic analyses were done using standard methods. The data obtained were analyzed using descriptive statistics and a student t-test. Significance was accepted at probability values of p < 0.05. The haematological effect of CPV-2 showed a significant (P < 0.05) decrease in mean Packed Cell Volume (PCV), total red blood cell count, haemoglobin concentration, total white blood cell count, neutrophils, lymphocytes and platelet count. In addition, the CPV-2 significantly (P < 0.05) increased the mean aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, triglyceride and malondialdehyde, while the mean total protein, sodium, potassium, chloride and cholesterol significantly (P < 0.05) decreased in the infected dogs. From the findings, CPV infection variably and significantly affected some haematological and serum biochemical parameters of infected dogs. Therefore, clinicians should endeavour to incorporate haematinics, haptatonics and immunemodulators during the management of canine parvoviral infection as supportive drugs with fluid therapy to improve the survivability of infected animals.
... However, according to our best literature knowledge, no study has been conducted investigating the relationship between oxidative stress and asymptomatic CEH in dogs. Oxidative stress can result in mutation and DNA damage in cells (Russo & Bracarense, 2016), thus leading to tissue damage and pathologies (Colitti et al., 2019), and has been also accused for the formation of many diseases (Russo & Bracarense, 2016) including uterine disease such as pyometra (Rautela & Katiyar, 2019). In addition, it is known that oxidative stress can promote the growth of endometrial cells and increase their adhesion, and therefore, there is a relationship between oxidative stress and endometritis in human (Amreen et al., 2019). ...
... However, according to our best literature knowledge, no study has been conducted investigating the relationship between oxidative stress and asymptomatic CEH in dogs. Oxidative stress can result in mutation and DNA damage in cells (Russo & Bracarense, 2016), thus leading to tissue damage and pathologies (Colitti et al., 2019), and has been also accused for the formation of many diseases (Russo & Bracarense, 2016) including uterine disease such as pyometra (Rautela & Katiyar, 2019). In addition, it is known that oxidative stress can promote the growth of endometrial cells and increase their adhesion, and therefore, there is a relationship between oxidative stress and endometritis in human (Amreen et al., 2019). ...
Article
Full-text available
This study aimed to investigate the differences in oxidative stress index (OSI) and kisspeptin levels in clinically asymptomatic dogs with cystic endometrial hyperplasia (CEH) compared to healthy and pregnant dogs, and to determine the usability of the obtained results in the diagnosis of asymptomatic CEH. The study comprised three groups; a healthy (n=8), a pregnant (n=10) and a CEH (n=10). All dogs in the three groups were included in the study at the 30±3th day after estrus, and blood samples were collected for analysis of kisspeptin, total antioxidant status (TAS), total oxidant status (TOS), progesterone (P4), estradiol (E2) and some biochemical parameters (TSH; thyroid stimulating hormone, ALT; alanine aminotransferase, AST; aspartate aminotransferase, ALP; alkaline phosphatase, LDH; lactate dehydrogenase, CRE; creatine and BUN; blood urea nitrogen). In addition, OSI value was calculated. P4 and ALT and BUN levels were significantly lower and higher in CEH group than the pregnant group, respectively (p < .05). While kisspeptin and TAS levels were significantly lower in CEH group compared to the healthy and pregnant groups (p < .01), OSI level increased dramatically. In conclusion, it was confirmed that CEH clearly affected kisspeptin and OSI levels, and it is thought that these parameters may be an alternative diagnostic tool for the detection of CEH after further studies.
... Hematological biomarkers [2,6] such as the percentage of neutrophil, lymphocyte [7], and neutrophil/lymphocyte [8] for the evaluation of stress response [2,7,8]. During cellular respiration, oxygen, the key element required to produce energy for the cellular metabolism and oxidation of organic compounds, is consumed and reduced, generating a series of highly reactive chemical substances called reactive oxygen species (ROS), also known as free radicals [9]. Oxidative stress is a phenomenon caused by an imbalance between production and accumulation of ROS [10]. ...
... In general, the trauma of a surgical procedure may contribute to oxidative stress [11]. The result of the reactions of ROS with biomolecules is the formation of substances that can be used as markers of oxidative damage [9] such as malondialdehyde (MDA) [11]. To counteract the harmful effects taking place in the cell, the system has evolved with some strategies such as prevention of damage, repair mechanism to alleviate the oxidative damages, physical protection mechanism against damage, and the final most important is the antioxidant defense mechanisms. ...
Article
Full-text available
Background and aim: Ovariohysterectomy (OHE) is a common procedure for sterilization of female dogs. However, knowledge of changes in pain stress, oxidative stress, and total antioxidant power status before, during, and after OHE is limited. The objective of this experiment was to study the effect of duration on pain stress, oxidative stress, and total antioxidant power status in female dogs undergoing OHE. Materials and methods: Seven female dogs were sterilized using the OHE method. Pain scores, hematological changes, and biochemical markers were investigated during pre-operative, 3 h after starting OHE, and on days 3, 7, 10, and 14 of an experimental period. Data were analyzed using one-way analysis of variance. Results: At 3 days after OHE, pain score was higher than on days 7-14 of the experimental period; percentage of neutrophil, 3 h after starting OHE, was higher than during pre-operative and on days 3-14 of the experimental period; percentage of lymphocyte on days 10-14 was lower than during pre-operative, 3 h after starting OHE, and on days 3-7 of the experimental period; neutrophil/lymphocyte ratio, 3 h after starting OHE, was higher than during pre-operative and on days 3-14 of the experimental period; plasma malondialdehyde on day 3 was higher than during pre-operative, 3 h after starting OHE, and on days 3-14 of the experimental period; and total antioxidant power on day 14 was higher than during pre-operative, 3 h after starting OHE, and on days 3-10 of the experimental period, respectively. Conclusion: This experiment indicated that OHE caused pain stress, oxidative stress, and reduction of total antioxidant power in female dogs. Finally, female dogs needed antioxidant for 7 days after OHE.
... However, other studies have shown the antioxidant properties of carvedilol against doxorubicin only through in vitro biochemical tests (Spallarossa et al., 2004) and in rats (Matsui et al., 1999). No statistically significant difference was observed in lipid peroxidation (TBARS) and protein oxidation (Carbonyl) and this may be due to the lack of standardization of the diet (Quiles et al., 2002;Sechi et al., 2017), environmental conditions and genetic diversity (Russo and Bracarense, 2016) in our study. However, TRAP assay (for evaluation of nonenzymatic antioxidant capacity of serum) (Mulholland and Strain, 1990;Palmieri and Sblendorio, 2007) showed difference between groups at baseline and there was no significant difference after chemotherapy even though it decreased in carvedilol and increased in placebo. ...
Article
The aim of this pilot study was to evaluate the cardioprotective effects of carvedilol in dogs receiving doxorubicin chemotherapy and provide suggestions to future studies based on results and limitations of our study. Thirteen dogs were randomized into two experimental groups: 6 dogs in carvedilol group and 7 dogs in placebo group. In carvedilol group, 0.39 mg/kg ± 0.04 twice-daily oral carvedilol was started on the day of the first doxorubicin treatment and continued throughout the chemotherapy protocol until the final cardiological evaluation. Cardiological evaluations were performed before the first doxorubicin administration and then 10 to 15 days after each subsequent dose. Troponin I and oxidative stress tests were performed with serum collected from dogs at the initial and final cardiological evaluation. Carvedilol produced some echocardiographic and electrocar-diographic changes (reduced E velocity and E/IVRT ratio, as well reduced heart rate and increased PR and QT interval) due to its beta-block effect. In placebo group Doppler study showed a significant increase in mitral flow deceleration time (EDT), as well increased amplitude of the S wave in the right, and R wave in the left, precordial chest leads. There were significant difference in the EDT, E/IVRT and A' velocity, as well heart rate, PR interval and R wave in V4/CV6LU precordial chest lead between groups. In conclusion, some indexes of diastolic function and in precordial chest leads were less affected by doxorubicin in carvedilol than in control group. This suggests that carvedilol may have a beneficial effect in canine cancer patients receiving doxorubicin.
... However, when considering the canine species, there are no studies assessing oxidative stress at a postprandial state and these markers have been widely used in dogs for pathological conditions such as uremia Bosco et al., 2016;Silva et al., 2013), leishmaniasis de Almeida et al., 2017), sarcoptic mange (Beigh et al., 2016), lymphoma (Bottari et al., 2015), breast carcinoma (Machado et al., 2015), ehrlichiosis (Rubio et al., 2017c), periodontal disease (Silva et al., 2018), reproductive disorders (Andrade et al., 2010), inflammatory bowel disease (Rubio et al., 2017b), among others. Considering that OS has been associated with several pathological conditions and that its analysis has been increasingly performed in dogs (Russo and Bracarense, 2016), knowledge of the factors that are capable of affecting the assessment of oxidative stress in dogs is of paramount importance. ...
Article
Oxidative stress (OS) has been strongly associated with postprandial lipemia (PPL) in humans, and still requires further investigation in dogs. However, since lipemia interferes with spectrophotometric determinations such as those used to assess OS, the present study investigated the effect of PPL on OS parameters of healthy dogs. Twenty dogs had lipemic postprandial samples compared to the average of two non-lipemic moments. Subsequently, PPL was simulated in vitro using a commercial lipid emulsion and twelve pools of non-lipemic serum of these dogs were used to simulate the minimum, median and maximum concentrations of triglycerides obtained during the lipemic state. Serum OS parameters were assessed using the antioxidants uric acid, albumin and total bilirubin; total antioxidant capacity (TAC); total oxidant capacity (TOC); and lipid peroxidation. In vivo PPL caused an increase in albumin, TAC-CUPRAC, TAC-FRAP, uric acid (p < 0.0001), TOC (p = 0.0012) and total bilirubin (p = 0.0245); reduction of TAC-ABTS (p = 0.0008); and did not alter the lipid peroxidation (p = 0.8983). In vitro, levels of albumin increased at the three lipemic concentrations (p < 0.0001), uric acid increased in the median and maximum levels (p < 0.0001), and total bilirubin concentration increased only at the maximum lipemic level (p = 0.0012). All lipemic levels tested increased TAC-ABTS (p = 0.0011) and TAC-FRAP (p < 0.0001). TAC-CUPRAC (p = 0.5002), TOC (p = 0.5938) and lipid peroxidation (p = 0.4235) were not affected by in vitro lipemia. In conclusion, both the in vivo postprandial state and in vitro simulated lipemia affect oxidative stress markers in dogs depending on the oxidative stress marker, and thus the postprandial state and/or lipemic samples should be avoided.
... Repeated consumption of diets containing high concentration of peroxides (>10 meq/kg) can cause liver related diseases (e.g. liver cirrhosis, fatty liver, etc.), diabetes, vascular disorders, cataract, atherosclerosis, etc. in dogs (Russo and Bracarense, 2016;Yagi, 1987). Whereas, repetitive feeding of fishes with diet containing high PV (>10 meq/kg) could cause pathological conditions such as inflammation and haemorrhage of fins. ...
Article
Hermetia illucens meal is one of the most promising alternatives to fishmeal and soymeal. Fat oxidation quality of these products is crucial, as it directly influences the palatability of feed, and health of animals consuming it. During this study, oxidative quality of commercial H. illucens meal, fishmeal and soymeal was evaluated by measuring fatty acid profile, free fatty acid content, peroxide value, p-anisidine value and electron spin resonance spectra of lipid free radicals. Fishmeal and soymeal used in this study had antioxidants, either added (in fishmeal), or naturally present (in soymeal), whereas H. illucens meal had no added antioxidants. Results indicate that fishmeal contain high levels of lipid free radicals and secondary oxidation products, which may adversely affect the health of the animal consuming it. In contrast, H. illucens meal and soymeal are stable in terms of oxidative quality. The majority of soymeal consumed in Europe originates from South America, where soy farming is linked to several social and environmental challenges. H. illucens meal could be a local and sustainable alternative to fishmeal and soymeal. Oxidative stability of H. illucens meal could be attributed to the short supply chain and careful design of the thermal processing step. In case of H. illucens meal, thermal processing is effective enough to deactivate sn-1,3-lipase, while causing minimal damage to unsaturated triglycerides. H. illucens meal contain high levels of saturated fats and is thermally processed at mild conditions in comparison to fishmeal and soymeal. This may offer advantage to H. illucens meal in terms of fat oxidation quality.
... The reason of observed elevation in SOD level in mange affected dogs may be attributed to its role as the first-line defense antioxidant as it help the body to remove the superoxide radicals by converting it to hydrogen peroxide (H 2 O 2 ) (Singh et al. 2014;Abdulaziz et al. 2019). Additionally, some authors suggest that the increase in the antioxidant enzymes is not necessarily desirable, as the antioxidant enzymes are not always decreased in disease conditions (Russo and Bracarense 2016). After antioxidant supplement, SOD was significantly lower than group treated with specific treatment and these alterations may suggest that antioxidant therapy was helpful for relief of oxidative stress, and therefore, it can be used as an aid to accelerate clinical recovery, but no significant changes occur in tickand flea-infested group. ...
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Skin diseases are among the most common health problems in dogs. The study aimed to evaluate the oxidative stress biomarker profile in mange-, tick-, and flea-infested dogs and to assess the value of antioxidant supplementation as complementary therapy to standard treatment. Thirty-seven dogs were enrolled in the study, and they were divided into three groups: apparently healthy group (11 dogs), mange group (8 dogs), and tick- and flea-infested group (18 dogs). Four dogs out of mange group and eleven dogs out of tick- and flea-infested group were treated with specific therapy supplemented with vitamin E and selenium (tocopherol 50 mg + Se 1.5 mg/ml) 0.5 ml/20 kg IM weekly in mange group and vitamin E capsule at dose of 40 IU/Ib in ticks and fleas group for 3 weeks as antioxidant therapy. Oxidative stress biomarkers were measured including SOD, GPX, catalase, and MDA. In mange group, there were significant increase in SOD, MDA, and significant decrease in GPX, catalase enzymes in diseased groups, while after treatment SOD was significantly decreased in antioxidant supplemented group only. Catalase was significantly increased, MDA was significantly decreased in specific and antioxidant supplemented groups but no significance differences between two types of treatment were noticed. In tick- and flea-infested group, there were significant decrease in GPX and increase in MDA in diseased groups; after treatment there were significant increase in GPX and catalase only in antioxidant supplemented group and significant variances between two protocols of therapy in catalase level only. Vitamin E and selenium can be used with standard therapy to accelerate the clinical recovery of external parasitism in dogs.
... Obese dogs show a significant increase in serum leptin concentrations and a decrease in adiponectin, which has antiinflammatory action (Park et al., 2014). One of the adverse effects of hyperleptinemia includes oxidative stress mediated by the activation of 2010; Russo and Bracarense, 2016) including chronic renal failure (Bosco el al., 2017) and leishmaniasis (Almeida et al., 2013). ...
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High occurrence of obesity currently constitutes the main nutritional disease of the canine species. There is evidence that leptin increases during obesity in dogs. Hyperleptinemia is associated with increased neutrophil oxidative metabolism in obese humans and contributes to oxidative stress. However, in obese dogs, the probable relationship between this condition and the activation of the oxidative metabolism of neutrophils has yet to be established. Thus, we investigated the hypothesis that neutrophil activation and systemic oxidative stress occur in dogs with hyperleptinemia. A control group of 24 healthy dogs with a body condition score (BCS) of 4–5, an overweight group of 25 dogs with a BCS of 6–7, and 27 obese dogs with a BCS of 8–9, were composed. Two subgroups were formed composed of dogs with and without hyperleptinemia, grouped according to the 95% confidence interval obtained for plasma leptin values of the control group. Changes in obesity markers (body condition score, adiponectin and plasma leptin) and plasma oxidative stress (lipid peroxidation, total antioxidant and oxidant capacities and oxidative stress index) were measured in all the dogs selected. Neutrophil oxidative metabolism was evaluated in flow cytometry by superoxide production with the probe hydroethidine and by hydrogen peroxide production with the probe 2′,7′-dichlorofluorescein diacetate, with or without phorbol myristate acetate (PMA) stimulation. Apoptosis and neutrophil viability were quantified in a capillary flow cytometer using Annexin V–PE, with or without camptothecin apoptosis inducing effect. Obese dogs presented higher systemic oxidative stress, hyperleptinemia and preactivated neutrophils with accelerated apoptosis. Dogs with hyperleptinemia and obese dogs presented higher neutrophil superoxide production under PMA stimulation and the presence of systemic oxidative stress compared with control. To our knowledge, this is probably the first evidence that preactivation of the oxidative metabolism of circulating neutrophils occurs in dogs with hyperleptinemia, a condition that can induce systemic oxidative stress in the canine species.
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General anesthesia increases the production of reactive oxygen species (ROS), which can exacerbate or increase oxidative stress and thus affect the prognosis of surgical procedures. Oxidative stress has been implicated in the development of cardiovascular, dermatologic, oncologic, and other diseases in dogs, as well as ischemia and reperfusion injury. Some anesthetics, such as halogenated anesthetics, have been shown to stimulate the production of ROS, while others, such as propofol, have antioxidant properties. However, the antioxidant effects of these anesthetics may not be sufficient to counteract oxidative damage at the doses used clinically. Nevertheless, the effects of anesthetics should be considered to minimize oxidative damage during anesthesia in dogs to improve the outcome of procedures requiring general anesthesia. This mini-review addresses the current knowledge on oxidative stress during inhalational and intravenous anesthesia in dogs. There is still a lack of information on the management of anesthesia in dogs with respect to oxidative stress. Further research, including comprehensive clinical studies is needed to better understand oxidative injury mechanisms and improve perioperative protocols during anesthesia in dogs.
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Aim: In this study, it was aimed to investigate the effects of demodicosis on oxidative stress in dogs. Materials and Methods: The material of the study is based on a total of 32 dogs, 21 of which are diagnosed with demodicosis and 11 of which are healthy, with different ages, genders and breeds. Examination for diagnostic evaluation of demodex is performed by examining the samples under the microscope which are taken by trichogram and deep skin scraping methods. In order to evaluate the oxidative stress on dogs with demodicosis at pre and post treatment groups and the control group without demodex diagnosis, the values of SOD (Superoxide dismutase), GPX (Glutation Peroxidase), GSH (Glutation) as antioxidant and MDA (Malondialdehyde) as oxidant are investigated. Results ?: In clinical examinations, manifestations such as alopecia, erythema, generalized pruritus, hyperpigmentation, lichenification, pododermatitis, interdigital pruritus, lymphadenopathy are observed on dogs with demodicosis on pre and post treatment stages. In the analyzes performed in order to evaluate the oxidative stress, MDA 20.30 nmol/ml, GSH 4.9 nmol/ml, GPx 0.42 U/l, SOD 4.1 U/l are measured in dogs with clinical demodicosis. At the post treatment stage, the average values on the same dogs are measured as MDA 6.08 nmol/ml, GSH 8.11 nmol/ml, GPx 0.83 U/l, SOD 6.67 U/l, whilst in the control group they were measured as MDA 4.94 nmol/ml, GSH 9.73 nmol/ml, GPx 0.97 U/l, SOD 7.20 U/l. It is obtained that, GSH, GPx and SOD values in the control and post treatment groups are significantly higher (p˂0.001) and MDA value is lower (p˂0.001) than the clinical demodicosis group. Conslusion: In dogs with clinical demodicosis, compared to control and post-treatment, higher level of MDA which is oxidant and lower level of GSA, GPx and SOD which are antioxidants showed that demodex is caused oxidative stress.
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RESUMO Este estudo objetivou analisar os efeitos do treinamento físico sobre biomarcadores de estresse oxidativo e do metabolismo glicídico no músculo esquelético de ratos. Ratos Wistar adultos (90 dias) foram treinados por corrida em esteira na velocidade equivalente à transição metabólica aeróbio-anaeróbia (TT) e na velocidade 25% superior a esta (TS). Como controles foram utilizados ratos mantidos sedentários (S). Não houve diferença entre os grupos quanto aos biomarcadores de estresse oxidativos analisados (concentração das substâncias que reagem ao ácido tiobarbitúrico e atividade catalase). A captação de glicose e a produção de lactato foram reduzidas, enquanto a oxidação de glicose e a síntese de glicogênio não foram aumentadas no grupo TS em relação aos demais. O treinamento na intensidade 25% superior à transição metabólica aeróbio-anaeróbia induziu adaptações no metabolismo glicídico muscular na ausência de estresse oxidativo. Palavras-chave: Estresse oxidativo. Metabolismo. Treinamento físico.
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REVISÃO RESUMO: Diabetes mellitus (DM) é uma síndrome de etiologia múltipla caracterizada por hiperglicemia crônica. Esta hiperglicemia induz o aumento na produção de espécies reativas de oxigênio (ERO) e diminuição das defesas antioxidantes. Devido às complicações causadas pelo diabete, muitos indivíduos optam por terapias alternativas à base de plantas medicinais para amenizar seus efeitos. Sendo assim, nesta revisão de literatura, foram analisados e descritos diversos trabalhos experimentais com a utilização de animais diabéticos para comprovar os efeitos antioxidantes de algumas dessas plantas e verificar se os títulos e resumos disponibilizados nos artigos são compatíveis aos objetivos de nossa busca. ABSTRACT: Evidence of the antioxidant effect of medicinal plants used in the treatment of Diabetes mellitus in animals: an update. Diabetes mellitus (DM) is a syndrome of multiple etiology characterized by chronic hyperglycemia. This hyperglycemia induces increased production of reactive oxygen species (ROS) and decreased antioxidant defenses. Due to complications caused by diabetes, a large number of people have chosen medicinal plant-based alternative therapies to alleviate its effects. Thus, in this literature review, several experimental studies with the use of diabetic animals were analyzed to demonstrate the antioxidant effects of these plants and to verify if the titles and abstracts provided in the papers are compatible with the aims of our search.
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The hypothesis that the uremic compounds decrease the neutrophil oxidative metabolism in dogs, as occurs in humans was tested. Whole blood from 10 dogs was incubated with uremic and non-uremic homologous sera and the superoxide production by activated neutrophils was quantified by the nitroblue tetrazolium reduction test (NBT). The superoxide production generated by neutrophils in the presence of uremic serum was significantly decreased (P<0.05) in comparison with autologous and homologous sera with normal urea levels. It was concluded that the presence of components of uremic serum inhibits the ex vivo neutrophil oxidative metabolism in dogs, suggesting that, similarly to humans, dogs with renal failure may have the innate immunity response compromised.
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This study aims to test the hypothesis that, similarly to what occurs in uremia, dogs with prerenal azotemia suffer oxidative stress associated with changes in oxidative metabolism and apoptosis in neutrophils. For this purpose, fifteen normal dogs and ten with prerenal azotemia had lipid peroxidation determined by quantifying the malondialdehyde (MDA) and had plasma total antioxidant status evaluated, correlating them with the superoxide production and apoptotic index of neutrophils. MDA and plasma total antioxidant status were determined using commercial reagents. Using capillary flow cytometry, superoxide production and apoptosis were determined from isolated neutrophils of peripheral blood using the hydrithidine and Annexin V-PE probe system, respectively. Azotemic dogs (26.29±5.32g/L) had a lower concentration (p=0.0264) of the plasma antioxidant albumin than the control group (30.36±3.29g/L) and also had lower (p=0.0027) total antioxidant status (2.36±0.32 versus 2.73±0.24mmol/L), while no alterations were observed in plasma lipid peroxidation and superoxide production. It was concluded that, similarly to what occurs in uremia, prerenal azotemia causes oxidative stress and acceleration of neutrophil apoptosis in dogs.
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Unitermos: • Peroxidação lipídica • Radicais livres • Espécies reativas de • oxigênio e nitrogênio • Hidroperóxidos lipídicos • Malondialdeído • Isoprostanos
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Alterations in antioxidant status and oxidative stress have been documented in dogs with dilated cardiomyopathy (DCM). The purpose of this study was to more broadly assess this relationship in dogs with congestive heart failure (CHF). Malondialdehyde (MDA), 8-F-2 alpha-isoprostane, protein carbonyls, reduced (GSH) and oxidized (GSSG) glutathione, vitamins A, C, and E, and oxygen radical absorbance capacity (ORAC) were measured from a single venous blood sample from dogs with CHF secondary to DCM or chronic valvular disease (CVD) and in healthy controls. Nineteen dogs with CHF (14 CVD and 5 DCM) and 12 healthy controls were enrolled in the study. Concentrations of 8-F-2 alpha-isoprostane (CHF: 44.6 pg/mL [range, 27.1-98.0 pg/mL], controls: 25.3 pg/mL [range, 11.1-80.4 pg/mL]) but not MDA (CHF: 4.11 mu M [range, 1.89-6.39 mu M], controls: 3.88 mu M [range, 2.14-4.72 mu M]) or protein carbonyls (0.69 nmol/mg protein [range, 0.37-1.67 nmol/mg protein], controls: 0.80 nmol/mg protein [range, 0.40-1.14 nmol/mg protein]) were significantly higher in the dogs with CHF than in the controls. Vitamin E concentration (CHF: 2,215 mu g/dL [range, 916-3,499 mu g/dL], controls: 2,820 mu g/dL [range, 1,738-3,775 mu g/dL]) and GSH: GSSG (CHF: 12.0 [range, 3.69-30.1], controls: 22.7 [range, 12.5-227]) were significantly lower, whereas ORAC CHF: 824 mu mol Trolox equivalent/L [range, 304-984], controls: 497 mu mol Trolox equivalent/L [range, 258-759]) and vitamin C (CHF: 0.90 mg/dL [range, 0.55-102 mg/dL], controls: 0.72 mg/dL [range, 0.43-0.85 mg/dL]) concentrations were higher in dogs with CHF than in controls. Vitamin A concentrations were not different between dogs with CHF and controls. No differences in any of the parameters were detected between dogs with DCM versus those with CVD. Some antioxidant defenses are decreased in dogs with CHF, and some biomarkers of oxidative stress are increased in dogs with CHE The effect of dietary interventions to correct this imbalance in antioxidant defenses warrants further study.
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The chronic kidney disease (CKD) it is characterized by irreversible structural lesions that can develop progressively for uremia and chronic renal failure (CRF). In the CRF it happens the incapacity of executing the functions of maintenance of the electrolyte balance and acid-base, catabolitos excretion and hormonal regulation appropriately. When the mechanism basic physiopathology of the renal upset is analyzed, it is observed that present factors, predispose to the unbalance oxidative. Most of the time, the renal patient comes badly nurtured, with lack in reservations of vitamins and minerals, what reduces the antioxidant defense mechanisms, what favors the installation of the renal oxidative stress, with the formation of species you reactivate of reactive oxygen species (ROS), substances these potentially harmful to the organism. The reduction of the glomerular filtration rate (GFR) in the evolution of CKD in dogs and cats is a component for the installation of the renal oxidative stress. The ROS possesses important action in the kidneys, and these substances are highly reactivate, and when presents in excess damage lipids, proteins, DNA and carbohydrate, driving functional and structural abnormalities taking the cellular apoptosis and necrosis. Against the harmful potential action of these substances you reactivate, she becomes fundamental a delicate control of his production and consumption in the half intracellular, in other words, a balance of his concentration intra and extracellular. That is possible due to the activity of the antioxidants. Like this, to present literature revision had as objective describes the participation of the oxidative stress in CRF, as well as the mechanisms defenses against the harmful action of those substances.
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Multiple biochemical and immunohistochemical tests were performed to elucidate the role of oxidative stress during ascending-descending (A-D) myelomalacia by comparing dogs with this progressive terminal condition to dogs with chronic, focal spinal cord injuries (SCIs) and controls without SCI. Dogs with A-D myelomalacia exhibited increased biochemical markers for oxidative stress, including 8-isoprostane F2α and acrolein, as well as decreased endogenous glutathione with greatest changes occurring at the lesion center. Inflammation, as evident by the concentration of CD18+ phagocytes and hemorrhagic necrosis, was also exacerbated in the lesion of A-D myelomalacic spinal cord compared to focal SCI. The greatest differences in oxidative stress occurred at the lesion center and diminished distally in both spinal cords with A-D myelomalacia and focal SCIs. The spatial progression and time course of A-D myelomalacia are consistent with the development of secondary injury post-SCI. Ascending-descending myelomalacia is proposed as a clinical model that may further the understanding of the role of oxidative stress during secondary injury. Our results indicate that the pathology of A-D myelomalacia is also similar to subacute progressive ascending myelopathy in humans, which is characterized by recurrent neurodegeneration of spinal cord post-injury. Copyright © 2015. Published by Elsevier B.V.
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Numerous studies reported an increase of oxidative stress increases in both women and female laboratory animals after ovariectomy. However, there is little information about the evaluation of antioxidative/oxidative status in ovariectomized dogs. The purpose of this study was to examine the changes in oxidative stress markers after ovariohysterectomy (OHE) in female dogs. The study included eighteen healthy mongrel female dogs. Blood samples were collected immediately before surgery and 14 and 30 days after surgery. Following parameters of oxidative stress intensity were determined: the erythrocyte activity of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) as well as the plasma concentrations of thiobarbituric acid reactive substances (TBARS), radical cations of N,N, diethylpara-phenylene diamine (RC-DEPPD), sulfhydryl groups (SH groups), bityrosine and formylkynurenine. The activity of GSH-Px increased markedly, although not significantly, 14 days after OHE and then significantly decreased at 30 days after OHE. A significant increase in plasma TBARS, bityrosine and formylkynurenine concentrations and a decrease in SH group content were concurrently noted at 30 days after surgery. Acquired results suggested that a loss of control over ROS production occurred in female dogs after OHE, which could lead to oxidative stress in the late post-operative period. In conclusion, our findings indicated that OHE is related with the risk of oxidative stress in the late period after operations. Given that oxidative stress contributes to the pathogenesis of various diseases, this may suggest an increased risk of disorders in ovariectomized female dogs; however, further studies are necessary to confirm this hypothesis. © 2015 Blackwell Verlag GmbH.