Resea ch pape
Oxida i e s ess influence on enal dys unc ion in pa ien s wi h
obs uc i e jaundice: A case and con ol p ospec i e s udy
Da id Ma ínez-Cecilia
a,
n
, Ma ía Reyes-Díaz
b
, Juan Ruiz-Rabelo
c
, Manuel Gomez-Al a ez
c
,
Ca men Muñoz Villanue a
d
, José Álamo
b
, Jo di Mun ané
e
, F ancisco Ja ie Padillo
e
a
Gene al and Diges i e Su ge y Se ice, Complejo Hospi ala io de Toledo, A de Ba be , 30, 45071 Toledo, Spain
b
Depa men o Gene al Su ge y, Hospi al Uni e si a io Vi gen del Rocio, Se illa, Spain
c
Gene al and Diges i e Su ge y Se ice, Hospi al Uni e si a io Reina So ía, Co doba, Spain
d
S a is ics and Resea ch Se ice, Hospi al Uni e si a io Reina So ía, Co doba, Spain
e
Depa men o Gene al Su ge y, Hospi al Uni e si a io Vi gen del Rocio/CSIC/Uni e sidad de Se illa, Se illa, Spain
a icle in o
A icle his o y:
Recei ed 10 Oc obe 2015
Recei ed in e ised o m
21 Decembe 2015
Accep ed 22 Decembe 2015
A ailable online 29 Decembe 2015
Keywo ds:
Obs uc i e jaundice
Acu e enal ailu e
Oxida i e s ess
Cance
abs ac
Backg ound: Obs uc i e Jaundice (OJ) is associa ed wi h a significan isk o de eloping acu e enal
ailu e (ARF). The in ol emen o oxida i e s ess in he de elopmen o choles asis has been demon-
s a ed in di e en expe imen al models. Howe e , i s ole in he mo bidi y o human choles asis is a o
be elucida ed. The aim o he s udy was he e alua ion o oxida i e s ess ma ke s in blood om pa ien s
wi h OJ and i s ela ion o complica ions and benign/malignan e olu ion o choles asis. Me hods: A
p ospec i e c oss-sec ional s udy o 105 pa ien s wi h OJ and 34 con ol subjec s we e included. Se e al
ma ke s o li e unc ion and oxida i e s ess, such as lipope oxides (LPO), as well as educed glu a hione
(GSH), ca alase (CAT), supe oxide dismu ase (SOD) and glu a hione pe oxidase (GSH-Px) ac i i ies we e
assessed. Resul s: The pa ien s wi h OJ showed a ma ked inc ease in plasma le els o LPO, SOD and GSH,
while GSH-Px le els we e dec eased. The inc ease in lipid pe oxida ion p oduc s and he deple ion o
SOD ac i i y in blood we e also ela ed o enal dys unc ion. The highes le el o LPO was associa ed wi h
malignan e iology o he disease. The logis ic eg ession analysis showed ha he age o he pa ien and
he le els o LPO in blood we e p edic o s o enal dys unc ion in OJ pa ien s. Conclusions: This s udy
demons a es a co ela ion be ween oxida i e s ess and enal dys unc ion pa ien s wi h OJ.
&2015 The Au ho s. Published by Else ie B.V. This is an open access a icle unde he CC BY-NC-ND
license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
1. In oduc ion
The obs uc ion o ex ahepa ic bilia y ac esul s in he di-
la a ion o bile duc s wi h an accumula ion o hyd ophobic bile
acids in hepa ocy es. The oxic bilia y p oduc s, such as gly-
cochenodeoxichola e, as well as neu ophil mig a ion p omo e he
gene a ion o oxygen- ee adicals, unbalancing an ioxidan s a us
in he hepa ic pa enchyma [1]. Exogenous egula ion o oxida i e
s ess amelio a es li e inju y induced by expe imen al choles asis
[2–4]. The pa hogenesis o OJ in ol es a sys emic al e a ion ha
a ec s di e en ex ahepa ic issues. An inc ease in lipope oxida-
ion p oduc s is obse ed in ex ahepa ic issues, including kidney
and b ain, in animals subjec ed o OJ [5,6].
Acu e enal ailu e is a significan ad e se ou come o OJ, ob-
se ing a es o 6–18% [7], and is associa ed wi h a significan
mo bidi y and pos ope a i e mo ali y [8,9]. The adminis a ion o
mela onin educes lipid oxida ion in kidney du ing expe imen al
OJ [10]. Hypo ension and sepsis, seconda y o deple ion o ex a-
cellula fluid and myoca dial dys unc ion has p o en o be ele an
in he de elopmen o kidney disease in choles a ic pa ien s [11–
19]. Howe e , he ole o oxida i e s ess du ing enal complica-
ions o OJ has no been s udied in de ail.
The main objec i e o he p esen s udy was o assess he
co ela ion be ween he al e a ion o oxida i e s ess bioma ke s
in blood and he p esence o enal ailu e in pa ien s wi h OJ.
2. Me hods
2.1. Design o s udy
The s udy was designed as a p ospec i e c oss-sec ional ob-
se a ional s udy. 105 pa ien s wi h OJ we e en olled and
Con en s lis s a ailable a ScienceDi ec
jou nal homepage: www.else ie .com/loca e/ edox
Redox Biology
h p://dx.doi.o g/10.1016/j. edox.2015.12.009
2213-2317/&2015 The Au ho s. Published by Else ie B.V. This is an open access a icle unde he CC BY-NC-ND license (h p://c ea i ecommons.o g/licenses/by-nc-nd/4.0/).
Abb e ia ions: OJ, obs uc i e jaundice; ARF, acu e enal ailu e; LPO, lipope -
oxides; GSH, educed glu a hione; CAT, ca alase; SOD, supe oxide dismu ase; GSH-
Px, glu a hione pe oxidase; MDRD, modifica ion o die in enal disease; GFR,
glome ula fil a ion a e; MDA, malondialdehyde; AP, alkaline phospha ase
n
Co esponding au ho .
E-mail add ess: [email p o ec ed] (D. Ma ínez-Cecilia).
Redox Biology 8 (2016) 160–164
compa ed wi h 34 heal hy subjec s, ma ched by sex, age, weigh ,
heigh , and body mass index. The pa ien s we e included o e a
pe iod o 26 mon hs. Inclusion c i e ia we e OJ o benign o malign
e hiology, le els o conjuga ed bili ubin highe han 2 mg/dl o
o al bili ubin highe han 3 mg/dl, biochemical choles a ic pa -
e n, ul asound e idence o ex ahepa ic bile duc dila a ion
highe han 12 mm and in ahepa ic highe han 4 mm. Exclusion
c i e ia we e acu e cholangi is, pa enchymal li e disease, gas o-
in es inal hemo hage, p io o concomi an in a enous fluid
he apy, hea ailu e o ch onic enal ailu e, unde nou ished
pa ien s, and ea men wi h diu e ics, an ihype ensi es, cime i-
dine o ime hop im. In o med consen was ob ained om all
pa icipan s.
The s udy was app o ed by he E hical Commi ee o Clinical
Resea ch o he Ins i u ion.
2.2. Biochemical measu emen s
Biochemical and oxida i e s ess pa ame e s we e measu ed on
pa ien s pe iphe al blood samples while admission o hospi al.
Same de e mina ions we e pe o med in con ol subjec s unde
simila condi ions o baseline measu emen s in pa ien s wi h ob-
s uc i e jaundice. The le els o di ec and o al bili ubin, sodium,
po assium, AST, ALT, alkaline phospha ase (AP), albumin and o al
p o ein we e pe o med wi h Cobas In eg a Roche-400 analyze
(Roche Diagnos ics L d., Swi ze land). Renal unc ion was es i-
ma ed by he modified o mula known as MDRD (Modifica ion o
Die in Renal Disease) [20]. Renal impai men was conside ed
when he glome ula fil a ion a e (GFR) alue was 70 ml/min
(1.73 m
2
). GFR was measu ed acco ding o he MDRD using he
ollowing he o mula:
=×[ ]− ×()
–×( )×( )
MDRD 186 c ea inine, mg/dl 1.154 age
0.203 0.742 in women 1.212 i black popula ion
2.3. Oxida i e s ess ma ke s
The ma ke s o oxida i e s ess we e assessed in plasma ob-
ained a e blood cen i uga ion a 3000 g o 5 min a 4 °C.
Samples we e s o ed a 80 °C un il measu emen s.
LPO and GSH we e de e mined using comme cial assays (LPO-
586 and GSH-400, Bioxy ech SA, Oxis In e na ional, Po land, OR,
USA). CAT and SOD we e measu ed acco ding o Aebi [21] and Sun
[22] me hods, espec i ely. GSH-Px was measu ed acco ding o
Flohe and Gunzle [23] me hod. The alues we e measu ed using a
pla e eade spec opho ome e Shimadzu UV-1603 (Shimadzu,
Kyo o, Japan).
2.4. S a is ical analysis
Resul s a e exp essed as mean7s anda d de ia ion (SD).
Compa isons be ween wo g oups we e pe o med using S uden 's
es o unpai ed g oups o Mann–Whi ney. Compa isons be-
ween h ee g oups we e pe o med using ANOVA analysis ol-
lowed o pos -hoc K uskal–Wallis es . Compa isons be ween
p opo ions we e pe o med by chi-squa ed es . Co ela ions o
a iables we e e alua ed wi h Pea son coe ficien o Spea man ho
coe ficien . Mul i a ia e analysis was pe o med o iden i y ac o s
associa ed wi h enal dys unc ion. The main a iables conside ed
we e: e iology o jaundice, age, du a ion o jaundice, bili ubin,
sodium, po assium, AST, ALT, AP, albumin, o al p o ein, LPO, GSH,
GSH-Px, SOD, CAT. Linea and logis ic eg ession we e pe o med
wi h he es ima ed enal unc ion by MDRD. S epwise me hod was
used excluding a iables wi h PZ0.15 (S uden 's s a is ic o
linea eg ession and Wald s a is ic o logis ic eg ession).
3. Resul s
3.1. Oxida i e s ess in pa ien s wi h OJ. Co ela ion wi h enal
insu ficiency
Table 1 shows gene al demog aphic and biochemical cha -
ac e is ics o he Con ol and OJ g oups. OJ pa ien s (n¼105) we e
dis ibu ed in 67 men (64%) and 38 women (36%), wi h mean age
o 69712.8 yea s old (15–93 yea s) (Table 1). The le els o pe -
iphe al LPO, GSH and SOD concen a ion we e significan ly highe
in he g oup o pa ien s wi h OJ compa ed o con ol subjec s
(p¼0.0001) (Table 1). By con as , le els o GSH-Px showed a
significan decline (p¼0.0001) (Table 1).
A s ong posi i e co ela ion was ound be ween le els o
conjuga ed bili ubin and LPO in plasma ( ¼0.744, p¼0.0001)
(Fig. 1).
The c ea inine clea ance in con ol subjec s (98731.1) was
significan ly highe han in OJ pa ien s o benign e hiology
(56725.9, p¼0.031). The e we e no s a is ically significan di -
e ences wi h c ea inine clea ance in pa ien s wi h malign
e hiology (72735.2, p¼0.199). The GFR o con ol subjec s
(104738.2 ml/min) was highe han in OJ pa ien s o benign
e hiology (84737.9 ml/min, p¼0.010) wi h a mode a e non s a-
is ically significan imp o emen in he malign e hiology
(116793.3 ml/min, p¼0.184). Renal ailu e was p esen in 32% o
he pa ien s, whe eas i was only obse ed in 6% o con ols. The
p esence o enal insu ficiency in pa ien s wi h OJ was associa ed
wi h highe le els o o al bili ubin (p¼0.002), as well as an in-
c ease in se um le els o LPO (p¼0.017) and GSH (p¼0.017) (Ta-
ble 2). By con as , he le els o SOD showed a dec ease in pa ien s
wi h enal impai men (p¼0.044) (Table 2). The e we e no s a-
is ically significan di e ences in he le els o GSH-Px and CAT
le els (Table 2).
A weak nega i e co ela ion was ound be ween plasma le els
o LPO and he GFR ( ¼0.303, p¼0.001) (Fig. 2).
3.2. Analysis o pa ien s wi h OJ acco ding o he benign/malign
e hiology
The e we e no significan di e ences among he pe cen age o
gende (men) in pa ien s wi h benign (n¼33, 31.5%) and malign
(n¼72, 68.5%) choles asis (Table 3). The inc eased le els o o al
(20711.5 s 12 77.4, p¼0001) and di ec bili ubin (1679.6 s
976.0, p¼0001), and AP (7577554.3 s 5287577.3, p¼0.005) in
blood om pa ien s wi h OJ o malign s benign e iologies e-
spec i ely, was p obably due o he longe e olu ion pe iod o he
disease (mean du a ion o jaundice 18 s 9 days) (Table 3). LPO
le els we e also highe in malignan e iology g oup. (6037202.0
s 4737144.8 nmol/l) (p¼0.0001) (Table 3).
3.3. Mul iple linea eg ession analysis
Di e en a iables such as age, du a ion o jaundice, bili ubin,
sodium, po assium, AST, ALT, albumin, o al p o eins, GSH, SOD
and CAT we e elimina ed om he model using he mul iple F
pa ial es (F¼0.2764, p¼0.735; eedom deg ee¼12.53). The
mul iple linea eg ession analysis o GFR es ima ed by he MDRD
o mula ulfilled he condi ions o p ope applica ion such as lin-
ea i y o independen a iables, no co-linea i y and independence
among hem, no mali y o esidues and homoscedas ici y o
a iances.
The linea adjus ed equa ion o he GFR in OJ pa ien s was:
D. Ma ínez-Cecilia e al. / Redox Biology 8 (2016) 160–164 161
=+[ ]
+[ ]−( )−( )
+( − )
MDRD 67.74 29.57 i benign e iology
77.06 i malignan e iology AP 0.03 0.07 LPO
2.22 GSH Px
The adjus ed coe ficien o de e mina ion (R2) was 0.171, and F
alue was 5.485 (p¼0.0001). The s a is ical associa i e model in-
dica ed ha 1 nmol/L inc ease o LPO will dec ease MDRD es i-
ma ion in 0.07 ml/min (IC95¼0.01). In addi ion, 1 U/L inc ease o
GSH-Px will inc ease MDRD es ima ion in 2.2 ml/min (IC95¼1.1).
3.4. Logis ic eg ession analysis
Di e en a iables (e iology, du a ion o jaundice, bili ubin,
sodium, po assium, AST, ALT, AP, albumin, o al p o eins, GSH,
GSH-Px, SOD and CAT) we e elimina ed om he model. The lo-
gis ic eg ession analysis demons a ed ha isk ac o s o enal
dys unc ion ollowed he equa ion:
=−+()+()
Z
5.791 0.044 age 0.003 LPO
The alue o he likelihood a io es was 12.532 (p¼0.002) and
Hosme –Lemeshow C alue was 5.604 (p¼0691). The s a is ical
associa i e model indica ed ha he isk o enal dys unc ion
measu ed by MDRD was 1.05 imes highe each yea o age (5% isk
inc ease pe yea ). Mo eo e , o e e y inc ease o 10 uni s o LPO,
he isk o enal dys unc ion was 1.031 imes g ea e (3% isk
inc ease).
4. Discussion
Redox imbalance associa ed wi h OJ has been ex ensi ely de-
mons a ed in expe imen al animal models [24,25]. Howe e ,
he e is a significan lack o e idence o his associa ion in hu-
mans. Assimakopoulos e al. showed an al e a ion o oxida i e
s a us in in es inal issue ha may unde lie he sys emic en-
do oxemia in OJ pa ien s [6]. Mon illa e al. showed an exace ba-
ion o hepa ic lipope oxida ion wi h educ ion o an ioxidan
s a us induced by liga u e o ex a-hepa ic bilia y duc in a s [3].
The p esen s udy demons a ed ha lipope oxida ion ma ke s in
blood a e inc eased in pa ien s wi h OJ in ela ion o he enal
dys unc ion and he benign o malign e hiology.
The neoplas ic o igin o he OJ was ela ed o a longe e olu ion
o he disease han ha obse ed in he benign choles a ic e iol-
ogy. In conco dance wi h p e ious s udies [26–29], he p og es-
sion o he disease was ela ed o he p og ession o ma ke s o
choles asis (Table 3).
The e idences o he co ela ion be ween oxida i e s ess,
enal dys unc ion and p og ession o OJ we e ein o ced in he
p esen s udy. We obse ed a d as ic educ ion o enal unc ion in
pa ien s wi h OJ o benign o igin wi h a mild no significan e-
co e y in pa ien s wi h malignan e iology. O e all, enal ailu e
was p esen in 32% o he pa ien s, whe eas i was only obse ed
in 6% o con ol subjec s. A p e ious clinical s udy had epo ed a
10% enal dis unc ion no ela ed o he e iology in a coho o 55
pa ien s wi h OJ [30]. This highe a e in ou s udy was p obably
ela ed o he use o highe h eshold o conside ing enal in-
su ficiency (GFR less han 70 ml/min ins ead o 50 ml/min), he
elec ion o a mo e accu a e me hod o measu e kidney unc ion,
inc eased numbe o pa ien s and hei dis ibu ion acco ding o
Table 1
Demog aphic cha ac e is ics and biochemical pa ame e s o he coho s.
Con ol Jaundiced p
n
Gende (%, men) 64% 71% 0.607
Age (yea s) 57716.5 69712.8 0.001
Weigh (Kg) 73713.9 73.3717.5 0.839
Heigh (cm) 16279.4 161715 0.923
Sys olic blood p essu e (mmHg) 122712.8 122.3720 0.730
Dias olic blood p essu e (mmHg) 73710.6 70711.9 0.224
Tempe a u e (°C) 3770.5 3670.4 0.634
To al Bili ubin (mg/dl) 0.50070.2 17.5711.00 0.001
Di ec Bili ubin (mg/dl) 0.23070.21 13.979.25 0.001
AP(U/L) 66727.1 6847569.2 0.001
GGT (U/L) 687106.6 6697537.5 0.001
LPO (nmol/L) 163782.8 5637195 0.001
GSH (nmol/L) 1.8071.000 10.775.3 0.001
GSH-Px (U/L) 22.878.50 15.1711.80 0.001
SOD (U/L) 15.1711.100 168 795.0 0.001
CAT (U/L) 3.872.10 4.874.90 0.124
n
Le el o s a is ical significance ob ained wi h S uden 's es o Mann–
Whi ney, as app op ia e.
Fig. 1. Co ela ion be ween se um bili ubin and LPO concen a ion in blood om pa ien s wi h OJ.
Table 2
Di ec bili ubin and oxida i e s ess pa ame e s in blood om pa ien s wi h OJ
acco ding o enal unc ion.
No mal
**
Func ion
GFRZ70 (ml/min)
Impai men
nn
GFRo70 (ml/min)
p
n
Di ec Bili ubin
(mg/dL)
8.91 (9–12) 14.53 (10–24) 0.002
LPO (nmol/L)) 428.76 (46–211) 588.03 (79–289) 0.017
GSH (nmol/L) 7.67 (5–60) 11.01 (5–71) 0.012
GSH-Px (U/L) 17.53 (12–88) 14.78 (5–15) 0.497
SOD (U/L) 145.48 (62–488) 99.74 (58–196) 0.044
CAT (U/L) 4.75 (5–16) 3.96 (2–90) 0.541
nn
The esul s we e exp essed wi h he median and he ange alues in pa -
en hesis.
n
Le el o s a is ical significance ob ained wi h S uden 's es o Mann–
Whi ney, as app op ia e.
D. Ma ínez-Cecilia e al. / Redox Biology 8 (2016) 160–164162
he e iology. The con ol g oup was significan ly younge han he
pa ien coho . As glome ula fil a ion a e dec eases wi h aging,
he au ho s can no exclude a selec ion bias. This will be discussed
la e . The oxida i e s ess ma ke s showed a mo e in ense lipid
pe oxida ion in plasma om pa ien s wi h OJ and enal dys unc-
ion (Table 2). The al e a ion o GFR (GFRo70 ml/min) was e-
la ed o an inc ease o pe iphe al LPO and GSH, and a educ ion o
SOD (Table 2).
Ano he key aspec o he s udy was he co ela ion be ween
oxida i e s ess ma ke s and disease p og ession. Le els o o al
bili ubin, di ec bili ubin, AP and GGT we e p og essi ely in-
c eased om benign o malignan e olu ion p obably as a con-
sequence o he longe e olu ion o he disease (Table 3). In his
si ua ion, he le els o LPO we e much highe in blood om pa-
ien s wi h OJ han in con ols, eaching he highes le els in hose
wi h malignan o igin (p¼0.0001).
A s ong posi i e co ela ion was obse ed be ween he le els
o lipope oxides and bili ubin in blood (Fig. 1) which was in con-
co dance wi h p e ious epo s showing he p o-oxidan capaci y
o oxic bile acids [31]. The inc eased le els o LPO we e associa ed
wi h a ise o GSH and SOD and educ ion o GSH-Px in blood om
jaundiced pa ien s wi h benign e hiology (p¼0.0001). Al hough
he endency o blood le els o an ioxidan s (GSH and SOD) was o
inc ease in bo h g oups o pa ien s (benign and malign), he di -
e ence be ween OJ e iologies did no each s a is ical significance
(Table 3). The explana ion may be ela ed o he accumula i e al-
e a ion o GSH, GSH-Px and SOD (exp ession o ac i i y) in he
di e en compa men o he body (li e and ex ahepa ic issue,
and blood cells) by he sus ained oxida i e s ess in pa ien s wi h
OJ o malignan o igin. In ac , he p og ession o expe imen al
jaundice (14 and 21 days) pa alleled he inc ease o LPO and he-
molysis, and educ ion o o al GSH con en in blood om ob-
s uc ed a s [32]. In his s udy, he le el o GSH-Px in li e was
educed h oughou all he s udy [32].
Se e al expe imen al s udies [32] ha e demons a ed a educ-
ion o plasma and hepa ic le els o GSH in OJ, which end o e-
co e a e he apeu ic in e en ion. The plasma le els o GSH
we e a ound 10 imes highe in pa ien s wi h OJ compa ed o
hose obse ed in con ol subjec s (Table 3). The in e p e a ion o
his phenomenon may lie o he s ong esponse o he body o
adap o he condi ions o oxida i e s ess inc easing he syn hesis
o GSH du ing choles asis. As a as we know, ou s udy is he fi s
epo ing GSH con en in blood om pa ien s wi h OJ. Da a will be
use ul o cla i y he beha io o his an ioxidan in ega d o i s
modula ion in li e o in es ine.
The mul iple linea eg ession model showed ha he benign
o malignan e hiology, AP, LPO and GSH-Px we e ela ed o enal
unc ion in pa ien s wi h OJ. This s udy demons a ed o he fi s
Fig. 2. Co ela ion be ween LPO concen a ion in blood and GFR in pa ien s wi h OJ.
Table 3
Demog aphic cha ac e is ics and biochemical pa ame e s o he coho s dis ibu ed
acco ding o benign and malignan o igin.
Con ol (n¼34) Benign e iol-
ogy (n¼33)
Malignan
e iology
(n¼72)
p*
Gende (%, men) 70% 61% 71% 0.533
Age 57716.5 66718.0 7079.4 0.013
a
0.001
b
0.818
c
Weigh (Kg) 73713.9 74718.3 73717.2 0.906
Heigh 16279.4 16379.3 160717.4 0.978
Sys olic blood
p essu e
(mmHg)
122712.8 121722.2 123720.1 0.938
Dias olic blood
p essu e
(mmHg)
73710.6 68712.9 70711.6 0.435
Tempe a u e (°C) 3770.5 3670.4 3670.4 0.889
Jaundice du a-
ion (days)
09.175.20 1878.6 0.001
c
To al Bili ubin
(mg/dl)
0.50070.2000 11.777.40 20.2711.50 0.001
a
0.001
b
0.001
c
Di ec Bili ubin
(mg/dl)
0.23070.2100 9.076.00 16.279.60 0.001
a
0.001
b
0.001
c
AP(U/L) 66727.1 5287577.3 7577554.3 0.001
a
0.001
b
0.005
c
GGT (U/L) 687106.6 6387548.2 6837535.7 0.001
a
0.001
b
0.791
c
LPO (nmol/L) 163782.8 4737144.8 6037202 0.001
a
0.001
b
0.001
c
GSH (nmol/L) 1.871.00 9.574.80 11.275.40 0.001
a
0.001
b
0.226
c
GSH-Px (U/L) 22.878.50 15.074.20 15.1714.00 0.001
a
0.001
b
0.170
c
SOD (U/L) 15.1711.10 52 752.6 2207287.8 0.001
a
0.001
b
0.281
c
CAT (U/L) 3.874.10 4.573.30 5.075.50 0.250
a
0.127
b
0.974
c
a
Compa ison be ween con ol and benign coho s.
b
Compa ison be ween con ol and malignan coho s.
c
Compa ison be ween benign and malignan coho s.
D. Ma ínez-Cecilia e al. / Redox Biology 8 (2016) 160–164 163
ime in humans he ela ionship be ween he inc ease o oxida i e
s ess ma ke s du ing OJ and he associa ed enal ailu e. Renal
unc ion was a ec ed by he in ensi y o he bilia y obs uc ion,
and he balance be ween LPO and an ioxidan de enses. The ac
ha age was no iden ified as a ec ing he glome ula fil a ion
a e es ima ion coun e ac s he p e iously exposed idea o a pos-
sible selec ion bias.
The logis ic eg ession analysis showed ha he age o he
subjec s and he le els o LPO in blood we e p edic o s o enal
dys unc ion in OJ pa ien s. A his poin we mus conside ha
glome ula fil a ion a e decline wi h aging could exp ess a sign
o no mal senescence ins ead o a disease. Fu u e esea ches
should conside di e en cu -o poin s o enal dys unc ion by
s a i ying by age g oups.
Rega ding edox imbalance, mul i a ia e analysis o e all con-
fi med he ela ionship be ween he oxida i e ma ke s in blood
and he in ensi y o OJ and enal dys unc ion.
In conclusion, ou s udy is he fi s epo showing in a la ge
se ies o pa ien s ha in si ua ions o OJ, he educ ion o GFR o
enal dys unc ion is ela ed o lipid pe oxida ion and al e a ion o
an ioxidan s a us in blood. The p og ession o he disease cha -
ac e is ic o malignan e iology was associa ed wi h an exace ba-
ion o lipid pe oxida ion.
Acknowledgmen s
This s udy has been suppo ed by he Ins i u o de Salud Ca los
III (PI 02/0155). CIBERehd was unded by he Ins i u o de Salud
Ca los III.
Re e ences
[1] L.Y. Tsai, K.T. Lee, T.Z. Lie, E idence o accele a ed gene a ion o hyd oxyl
adicals in expe imen al obs uc i e jaundice o a s, F ee. Radic. Biol. Med. 24
(1998) 732–737.
[2] R.J. Sokol, J.M. McKim, M.C. Go , e al., Vi amin E educes oxidan inju y o
mi ochond ia and he hepa o oxici y o au ochenodeoxycholic-acid in a ,
Gas oen e ology 114 (1998) 164–174.
[3] P. Mon illa, I. Tunez, M.C. Muñoz, e al., P o ec i e e ec o MEL agains oxi-
da i e s ess induced by liga u e o ex a-hepa ic bilia y duc in a s: com-
pa ison wi h he e ec o S-adenosyl-
L
-me hionine, J. Pineal Res. 28 (2000)
143–149.
[4] P. Mon illa, A. C uz, F.J. Padillo, e al., Mela onin e sus i amin E as p o ec i e
ea men agains oxida i e s ess a e ex ahepa ic bile duc liga ion in a s, J.
Pineal Res. 31 (2001) 135–139.
[5] P. Ljubuncic, Z. Tanne, A. Bomzon, E idence o a sys emic phenomenon o
oxida i e s ess in choles asic li e disease, Gu 47 (2000) 710–716.
[6] S.F. Assimakopoulos, A.G. Ma akis, K. G in zalis, e al., Supe oxide adical
o ma ion in di e se o gans o a s wi h expe imen ally induced obs uc i e
jaundice, Redox Rep. 13 (2008) 179–184.
[7] H.J. K ame , Impai ed enal unc ion in obs uc i e jaundice: oles o he
h omboxane and endo helin sys ems, Neph on 77 (1997) 1–12.
[8] B.J. Foga y, R.W. Pa ks, B.J. Rowlands, e al., Renal dys unc ion in obs uc i e
jaundice, B . J. Su g. 82 (1995) 877–884.
[9] F.J. Padillo, A. C uz, I. Espejo, e al., Al e a ion o he enal egula o y ho monal
pa e n du ing expe imen al obs uc i e jaundice, Re . Esp. En e m. Dig. 101
(2009) 408–412.
[10] A. C uz, F.J. Padillo, I. Túnez, Mela onin p o ec s agains enal oxida i e s ess
a e obs uc i e jaundice in a s, Eu . J. Pha macol. 425 (2001) 135–139.
[11] R.D. Williams, D.W. Ellio , R.M. Zollinge , The e ec o hypo ension in ob-
s uc i e jaundice, A ch. Su g. 81 (1960) 334–340.
[12] D.J. Gille , The e ec o obs uc i e jaundice on he blood olume in a s, J.
Su g. Res. 11 (1971) 447–449.
[13] A. Si ges-Se a, Renal ailu e in obs uc i e jaundice, in: V. A oyo, P. Gines,
P. Sch ie , J. Rodes (Eds.), Li e and Kidney., Blackwell Publishe s, Ox o d, 1999,
pp. 79–98.
[14] A. Si ges-Se a, X. Ca ulla, C. Pie a, e al., Body wa e compa men s in pa ien s
wi h obs uc i e jaundice, B . J. Su g. 79 (1992) 553–556.
[15] R.W. Pa ks, T. Diamond, D.C. McC o y, e al., P ospec i e s udy o pos ope a i e
enal unc ion in obs uc i e jaundice and he e ec o pe iope a i e dopa-
mine, B . J. Su g. 81 (1994) 437–439.
[16] F.J. Padillo, M. Rod iguez, J.M. Galla do, e al., P eope a i e assessmen o body
fluid dis u bances in pa ien s wi h obs uc i e jaundice, Wo ld J. Su g. 23
(1999) 681–687.
[17] J. G een, R. Beya , S. Sideman, e al., The “jaundiced hea ”: a possible ex-
plana ion o pos ope a i e shock in obs uc i e jaundice, Su ge y 100 (1986)
14–20.
[18] J. Padillo, J. Puen e, M. Gomez, e al., Imp o ed ca diac unc ion in pa ien s
wi h obs uc i e jaundice a e in e nal bilia y d ainage: hemodynamic and
ho monal assessmen , Ann. Su g. 234 (2001) 652–656.
[19] F.J. Padillo, B. Andicobe y, J. Mun ane, e al., Fac o s p edic ing nu i ional
de angemen s in pa ien s wi h obs uc i e jaundice: a mul i a ia e analysis,
Wo ld J. Su g. 25 (2001) 413–418.
[20] A.S. Le ey, J. Co esh, T. G eene, e al., Using s anda dized se um c ea inine
alues in he modifica ion o die in enal disease s udy equa ion o es i-
ma ing glome ula fil a ion a e, Ann. In e n Med. 145 (2006) 247–254.
[21] H. Aebi, Ca alase in i o, in: S.P. Colowick, N.O. Kaplan (Eds.), Me hods in
Enzymology, Volume 105, Academic P ess, O lando, 1984, pp. 121–126.
[22] Y. Sun, L.W. Obe ley, Y. Li, A simple me hod o clinical assay o supe oxide
dismu ase, Clin. Chem. 34 (1988) 479–500.
[23] L. Flohe, W.A. Gunzle , Assays o glu a hione pe oxidase, in: S.P. Colowick, N.
O. Kaplan (Eds.), 12 h ed.,Me hods in Enzymology, Volume 105, Academic
P ess, O lando, 1984, pp. 14–21.
[24] S. Yüceya , K. Gümüş aş, S. E ü k, e al., The ole o oxygen ee adicals in
acu e enal ailu e complica ing obs uc i e jaundice: an expe imen al s udy,
HPB Su g. 10 (1998) 387–393.
[25] C. Kucuk, E. Sozue , I. Ikizceli, e al., Role o oxygen ee adical sca enge s in
acu e enal ailu e complica ing obs uc i e jaundice, Eu . Su g. Res. 35 (2003)
143–147.
[26] F.J. Padillo, A. C uz, J. B iceño, e al., Mul i a ia e analysis o ac o s associa ed
wi h enal dys unc ion in pa ien s wi h obs uc i e jaundice, B . J. Su g. 92
(2005) 1388–1392.
[27] C.N. Yeh, Y.Y. Jan, W.C. Lee, e al., Hepa ic esec ion o hepa ocellula ca ci-
noma wi h obs uc i e jaundice due o bilia y umo h ombi, Wo ld J. Su g.
28 (2004) 471–475.
[28] F.J. Padillo, J. Mun ane, J.L. Mon e o, e al., E ec o in e nal bilia y d ainage on
plasma le els o endo oxin, cy okines, and C- eac i e p o ein in pa ien s wi h
obs uc i e jaundice, Wo ld J. Su g. 26 (2002) 1328–1332.
[29] F.J. Padillo, B. Andicobe y, J. Mun ane, e al., Cy okines and acu e-phase e-
sponse ma ke s de angemen s in pa ien s wi h obs uc i e jaundice, Hepa-
ogas oen e ology 48 (2001) 378–381.
[30] A. Uslu, M. Cayci, A. Na , e al., Renal ailu e in obs uc i e jaundice, Hepa-
ogas oen e ology 52 (2005) 52–54.
[31] R.J. Sokol, R. Dahl, M.W. De e eaux, e al., Human hepa ic mi ochond ia gen-
e a e eac i e oxygen species and unde go he pe meabili y ansi ion in e-
sponse o hyd ophobic bile acids, J. Pedia . Gas oen e ol. Nu . 41 (2005)
235–243.
[32] N. Alp ekin, G. Mehme çik, M. Uysal, e al., E idence o oxida i e s ess mi-
ochond ia o bile duc liga ed a s, Pha macol. Res. 36 (1997) 243–247.
D. Ma ínez-Cecilia e al. / Redox Biology 8 (2016) 160–164164