Co esponding au ho : Fa ma Gönül Sezgin; o cid: h ps://o cid.o g/0000-0002-9400-5173
Copy igh © 2025 Au ho (s) e ain he copy igh o his a icle. This a icle is published unde he e ms o he C ea i e Commons A ibu ion Liscense 4.0.
P o ec i e E ec s o cAMP and Coenzyme Q Agains Cispla in-Induced Li e Inju y
Fa ma Gönül Sezgin *
Depa men o Biology, Facul y o Science, Ondokuz Mayıs Uni e si y, Samsun, Tü kiye.
GSC Biological and Pha maceu ical Sciences, 2025, 32(03), 223-231
Publica ion his o y: Recei ed on 05 Augus 2025; e ised on 20 Sep embe 2025; accep ed on 22 Sep embe 2025
A icle DOI: h ps://doi.o g/10.30574/gscbps.2025.32.3.0368
Abs ac
Objec i e: This s udy aimed o in es iga e he e ec s o cyclic adenosine monophospha e (cAMP) and coenzyme Q
(CoQ), adminis e ed indi idually o in combina ion, on he hepa ic an ioxidan de ense sys em and oxida i e damage
ma ke s in a cispla in (Cis)-induced hepa o oxici y model.
Me hods: Wis a albino a s b ed a he Ondokuz Mayıs Uni e si y Expe imen al Animal Resea ch Cen e we e di ided
in o eigh g oups: con ol, Cis, CoQ, cAMP, CoQ+cAMP, Cis+CoQ, Cis+cAMP, and Cis+CoQ+cAMP. Supe oxide dismu ase
(SOD), ca alase (CAT), and glu a hione pe oxidase (GPx) ac i i ies as well as malondialdehyde (MDA) le els we e
measu ed in he li e issues ob ained om expe imen al g oups. Da a we e analyzed using he Mann-Whi ney U es .
Resul s: Cis adminis a ion caused ime-dependen luc ua ions in SOD, CAT, and GPx ac i i ies, along wi h an inc ease
in MDA le els. CoQ adminis a ion signi ican ly educed MDA le els a all ime poin s and imp o ed an ioxidan enzyme
ac i i ies. cAMP adminis a ion ma kedly dec eased MDA le els, pa icula ly in he ea ly phase (4–12 h), and modula ed
SOD and CAT ac i i ies. The combined adminis a ion o cAMP and CoQ enhanced GPx ac i i y in he la e phase (24–48
h) and exe ed he s onges supp ession o MDA le els.
Conclusion: The indings indica e ha cAMP is as e ec i e as CoQ in a enua ing cispla in-induced oxida i e s ess.
Bo h cAMP and CoQ exhibi ed hepa op o ec i e e ec s indi idually, while hei combina ion p oduced a syne gis ic
e ec , achie ing he highes deg ee o p o ec ion. These esul s may con ibu e o he de elopmen o no el
pha macological s a egies o mi iga e cispla in-associa ed hepa o oxici y.
Keywo ds: Cispla in; Li e Inju y; Oxida i e S ess; cAMP; Coenzyme Q; An ioxidan Enzymes; P o ec i e E ec
1. In oduc ion
Cispla in (Cis) is a b oad-spec um chemo he apeu ic agen widely used in he ea men o solid umo s. Despi e i s
e icacy, one o he mos signi ican limi ing ac o s in clinical applica ions is he se e e oxici ies i induces in a ious
o gans [1]. Hepa o oxici y is a c i ical ad e se e ec o Cis ha can lead o conside able mo bidi y in clinical p ac ice
[2]. As he li e plays a cen al ole in d ug bio ans o ma ion, i is pa icula ly ulne able o oxida i e s ess–media ed
inju y [3].
The unde lying mechanism o Cis-induced hepa o oxici y is associa ed wi h inc eased p oduc ion o eac i e oxygen
species (ROS), ele a ed lipid pe oxida ion, and imbalance in he an ioxidan de ense sys em [4,5]. Func ional al e a ions
o enzymes such as supe oxide dismu ase (SOD), ca alase (CAT), and glu a hione pe oxidase (GPx) play a pi o al ole in
his p ocess. In pa icula , ROS o e p oduc ion esul s in he oxida i e deg ada ion o memb ane lipids, leading o
malondialdehyde (MDA) accumula ion, which se es as a hallma k o cellula damage [5].
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Recen s udies ha e demons a ed ha oxida i e s ess is no only limi ed o classical cellula inju y bu also igge s
p og ammed cellula p ocesses such as e op osis and endoplasmic e iculum (ER) s ess [6]. The e o e, p o ec i e
s a egies agains Cis-induced hepa o oxici y a e sugges ed o in ol e agen s ha a ge mul iple pa hways, including
an ioxidan s and in acellula signaling egula o s [6,7].
In his con ex , coenzyme Q (CoQ) and cyclic adenosine monophospha e (cAMP) s and ou as no ewo hy molecules.
CoQ is an endogenous an ioxidan ha plays a c ucial ole in he mi ochond ial elec on anspo chain and has been
shown o a enua e oxida i e s ess– ela ed li e inju y in a ious expe imen al models [7,8]. On he o he hand,
ele a ion o in acellula cAMP le els p o ides hepa op o ec i e e ec s by ac i a ing CREB-media ed an ioxidan gene
exp ession and supp essing in lamma ion [9]. Recen s udies ha e epo ed ha cAMP-enhancing agen s, such as
phosphodies e ase-3 (PDE3) inhibi o s, alle ia e Cis-induced li e inju y [10].
The e o e, in es iga ing he p o ec i e e ec s o cAMP and CoQ, bo h indi idually and in combina ion, in a Cis-induced
hepa o oxici y model is o conside able impo ance o elucida ing he mechanis ic aspec s o oxida i e s ess and
guiding he de elopmen o no el pha macological s a egies.
2. Ma e ials and Me hods
In he s udy app o ed by he Ondokuz Mayıs Uni e si y E hics Commi ee wi h he decision numbe ed HEK/28, Wis a
albino a s weighing 250-300 g, b ed in he Ondokuz Mayıs Uni e si y Expe imen al Animal Resea ch Cen e (DEHAM),
we e used.
2.1. Expe imen al G oups
Eigh g oups we e o med as ollows:
Con ol g oup (no in e en ion), 2. Cis g oup, 3. CoQ g oup, 4. cAMP g oup,5. CoQ + cAMP g oup, 6. Cis + CoQ g oup,
7. Cis + cAMP g oup, 8. Cis + CoQ + cAMP g oup.
Each g oup consis ed o 5 a s. Injec ions we e adminis e ed be ween 08:00 and 09:00 a.m. Following injec ion, animals
we e sac i iced by ce ical disloca ion a 4, 8, 12, 24, and 48 hou s. A e pe usion wi h 0.9% NaCl, he li e s we e
excised and s o ed in 0.25 M suc ose solu ion a –80 °C un il analysis.
2.2. Adminis e ed Subs ances
Cis was used a a dose o 10 mg/kg (comme cial p epa a ion, 100 mg/100 mL) [11]. cAMP, ob ained om Calbiochem,
was adminis e ed a a dose o 15 mg/kg [12], and CoQ, ob ained om Sigma (London, England), was adminis e ed a a
dose o 371 mg/kg [13].
De e mina ion o Enzyme Ac i i ies and MDA Le els
• P o ein concen a ion was de e mined by he me hod o Low y e al. [14].
• CAT ac i i y was measu ed acco ding o he me hod o Lück [15].
• SOD ac i i y was de e mined by he me hod o McCo d and F ido ich [16] and u he alida ed by he me hod
o Flohé and O ing [17].
• GPx ac i i y was measu ed as desc ibed by Law ence and Bu k [18].
• MDA le els we e assessed using he me hod o D ape and Hadley [19], in addi ion o he hioba bi u ic acid
(TBA) assay desc ibed by Hommouda e al. [20].
S a is ical Analysis; Da a we e analyzed using he Mann-Whi ney U es , and p < 0.05 was conside ed s a is ically
signi ican .
3. Resul s
SOD Ac i i y: When he e ec o Cis on o al hepa ic SOD ac i i y was compa ed wi h he con ol g oup, inhibi ion was
obse ed wi hin he i s 8 hou s, while a he 12 h hou , a 45% ac i a ion was de ec ed. This ac i a ion dec eased a
he 24 h hou and e u ned o nea ly con ol le els a he 48 h hou (p > 0.05). Howe e , when he enzyma ic ac i i y
changes induced by Cis we e compa ed ac oss di e en ime poin s, signi ican di e ences we e obse ed (p < 0.05).
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cAMP adminis a ion esul ed in signi ican inhibi ion a all ime poin s (p < 0.05). Simila ly, CoQ adminis a ion caused
s a is ically signi ican inhibi ion ac oss all ime poin s (p < 0.05). In he Cis+cAMP g oup, compa ed wi h he con ol,
he 45% ac i a ion obse ed wi h Cis alone a he 12 h hou inc eased o 80% wi h he addi ion o cAMP (p < 0.05). In
he Cis+CoQ g oup, his ac i a ion eached 66% wi h CoQ supplemen a ion (p < 0.05). In he cAMP+CoQ g oup, 40%
inhibi ion was obse ed a he 4 h hou and 56.8% a he 8 h hou . A he 12 h hou , inhibi ion dec eased o 10.9%,
which shi ed o 1.6% ac i a ion a he 24 h hou and eached 45% ac i a ion a he 48 h hou . These enzyme ac i i y
changes we e s a is ically signi ican ac oss ime poin s (p < 0.05).
In he Cis+cAMP+CoQ g oup, 22% inhibi ion was obse ed a he 4 h hou and 35.8% a he 8 h hou , ollowed by 33.5%
ac i a ion a he 12 h hou . A he 24 h hou , 46% inhibi ion was eco ded, while a he 48 h hou , 31.8% ac i a ion
was no ed. The inhibi ion obse ed a he 8 h hou was s a is ically signi ican (p < 0.05). When compa ed ac oss
di e en ime poin s, signi ican di e ences we e obse ed be ween he 4 h and 48 h hou s (p = 0.028) and he 8 h and
48 h hou s (p = 0.028) (p < 0.05) (Figu e 1).
Figu e 1 Time-dependen change o SOD ac i i y acco ding o expe imen al g oups
CAT Ac i i y: Compa ed wi h he con ol g oup, Cis adminis a ion caused 13.6% and 18.5% inhibi ion in hepa ic CAT
ac i i y a he 4 h and 8 h hou s, espec i ely. A he 12 h hou , 31% ac i a ion was de ec ed, which dec eased o 20%
a he 24 h hou and e u ned o nea -con ol le els a he 48 h hou . Signi ican di e ences we e obse ed among ime
poin s (p < 0.05).
In he cAMP g oup, compa ed wi h he con ol, CAT ac i i y showed 5.7% inhibi ion a he 4 h hou and 30.9% a he
8 h hou , while 19.6% ac i a ion was obse ed a he 12 h hou . No di e ence was no ed a he 24 h hou , whe eas
36% ac i a ion occu ed a he 48 h hou . The changes in CAT ac i i y we e s a is ically signi ican a he 8 h (p = 0.028)
and 12 h hou s (p = 0.009).
In he CoQ g oup, inhibi ion was obse ed a he 4 h (2%) and 8 h (24%) hou s. This inhibi ion was 15.7% a he 12 h
hou and 18.9% a he 24 h hou , ollowed by 12.7% ac i a ion a he 48 h hou . These changes we e s a is ically
signi ican (p < 0.05).
In he Cis+cAMP g oup, CAT ac i i y showed 30.9% inhibi ion a he 4 h hou , which dec eased o 20% a he 8 h hou ,
and shi ed o 35.7% ac i a ion a he 12 h hou . A he 24 h and 48 h hou s, 20% inhibi ion was obse ed. The
di e ences a he 24 h and 48 h hou s compa ed wi h he con ol we e s a is ically signi ican (p < 0.05).
In he Cis+CoQ g oup, no di e ence was obse ed a he 4 h hou , while 21% inhibi ion occu ed a he 8 h hou . A he
12 h hou , inhibi ion was 2%, ollowed by 15% ac i a ion a he 24 h hou and 36% inhibi ion a he 48 h hou . The
di e ence a he 48 h hou was s a is ically signi ican (p < 0.05).
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In he Cis+cAMP+CoQ g oup, no di e ences we e no ed a he 4 h hou , while inhibi ion o 10% and 15% occu ed a
he 8 h and 12 h hou s, espec i ely. A he 24 h hou , 15% ac i a ion was eco ded, ollowed by 31% inhibi ion a he
48 h hou . The di e ence a he 48 h hou was s a is ically signi ican (p < 0.05). Di e ences among ime poin s we e
also signi ican (p < 0.05) (Figu e 2).
Figu e 2 Time-dependen change o CAT ac i i y acco ding o expe imen al g oups
GPx Ac i i y: In he Cis g oup, GPx ac i i y showed 37% inhibi ion a he 4 h hou compa ed wi h he con ol g oup,
while no di e ences we e obse ed a he 8 h and 12 h hou s. A he 24 h hou , 26% ac i a ion was no ed, which
inc eased o 33% a he 48 h hou . The inhibi ion obse ed a he 4 h hou was s a is ically signi ican (p < 0.05).
In he cAMP g oup, GPx ac i i y showed 84% inhibi ion a he 4 h hou and 51% a he 8 h hou compa ed wi h he
con ol. A he 12 h hou , 3% ac i a ion was eco ded, ollowed by no di e ence a he 24 h hou and 4% inhibi ion a
he 48 h hou . Inhibi ion a he 4 h hou was s a is ically signi ican (p < 0.05).
In he CoQ g oup, GPx ac i i y showed 85% inhibi ion a he 4 h hou and 24% inhibi ion a he 8 h hou . A he 12 h
hou , 30% ac i a ion was obse ed, which dec eased o 6% a he 24 h hou and inc eased o 37% a he 48 h hou .
Inhibi ion a he 4 h hou and ac i a ion a he 48 h hou we e s a is ically signi ican (p < 0.05).
In he Cis+cAMP g oup, GPx ac i i y showed 48% and 34% inhibi ion a he 4 h and 8 h hou s, espec i ely. A he 12 h
hou , 45% ac i a ion was no ed. A he 24 h and 48 h hou s, 23% inhibi ion and 22% ac i a ion we e obse ed,
espec i ely. The inhibi ion a he 4 h hou was s a is ically signi ican (p < 0.05).
In he Cis+CoQ g oup, GPx ac i i y showed 41% inhibi ion a he 4 h hou , ollowed by 22% ac i a ion a he 8 h hou .
A he 12 h hou , 39% inhibi ion was eco ded, ollowed by 40% ac i a ion a he 24 h hou and 15% inhibi ion a he
48 h hou . The inhibi ion a he 4 h hou was s a is ically signi ican (p < 0.05).
In he cAMP+CoQ g oup, GPx ac i i y showed 40% inhibi ion a he 4 h hou , 46% inhibi ion a he 8 h hou , and 42%
inhibi ion a he 12 h hou . A he 24 h hou , 37% ac i a ion was eco ded, which ma kedly inc eased o 130% a he
48 h hou . Di e ences ac oss ime poin s we e s a is ically signi ican (p < 0.05).
In he Cis+cAMP+CoQ g oup, GPx ac i i y showed 44% inhibi ion a he 4 h hou and 46% inhibi ion a he 8 h hou ,
which dec eased o 13% a he 12 h hou . A he 24 h hou , 103% ac i a ion was obse ed, ollowed by 44% inhibi ion
a he 48 h hou . These di e ences we e s a is ically signi ican (p < 0.05) (Figu e 3).
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Figu e 3 Time-dependen change o GPx ac i i y acco ding o expe imen al g oups
MDA Le els: In he Cis g oup, hepa ic MDA le els we e 7% lowe han he con ol a he 4 h hou bu inc eased by 20%
a he 8 h hou and 15% a he 12 h hou . A he 24 h and 48 h hou s, MDA le els we e 4% and 34% highe , espec i ely.
Al hough Cis adminis a ion led o an o e all inc ease in MDA le els a e he 4 h hou , hese inc eases we e no
s a is ically signi ican (p > 0.05). Howe e , di e ences among ime poin s we e s a is ically signi ican (p < 0.05).
In he cAMP g oup, hepa ic MDA le els we e educed by 84%, 83%, 68%, 75%, and 72% a he 4 h, 8 h, 12 h, 24 h, and
48 h hou s, espec i ely, compa ed wi h he con ol. These educ ions we e s a is ically signi ican a all ime poin s (p
< 0.05).
In he CoQ g oup, hepa ic MDA le els we e 81%, 77%, 75%, 85%, and 89% lowe a he 4 h, 8 h, 12 h, 24 h, and 48 h
hou s, espec i ely, compa ed wi h he con ol. All educ ions we e s a is ically signi ican (p < 0.05).
In he cAMP+CoQ g oup, MDA le els we e educed by 92%, 76%, 85%, 92%, and 84% a he 4 h, 8 h, 12 h, 24 h, and
48 h hou s, espec i ely. These educ ions we e s a is ically signi ican a all ime poin s (p < 0.05).
In he Cis+cAMP g oup, MDA le els we e 9% and 1% highe a he 4 h and 8 h hou s, espec i ely, compa ed wi h he
con ol, and 30% highe a he 12 h hou . A he 24 h and 48 h hou s, MDA le els we e 28.7% and 17% lowe ,
espec i ely. While hese changes we e no s a is ically signi ican compa ed wi h he con ol (p > 0.05), di e ences
ac oss ime poin s we e signi ican (p < 0.05).
In he Cis+CoQ g oup, MDA le els we e 28% highe a he 4 h hou compa ed wi h he con ol, 15% lowe a he 8 h
hou , 48% highe a he 12 h hou , 35% highe a he 24 h hou , and 3% lowe a he 48 h hou . These di e ences we e
no s a is ically signi ican (p > 0.05). Howe e , compa isons ac oss ime poin s e ealed signi ican di e ences (p <
0.05).
In he Cis+cAMP+CoQ g oup, MDA le els we e 9% highe a he 4 h hou , nea ly equal (1% highe ) o con ol a he 8 h
hou , and 30% highe a he 12 h hou . A he 24 h hou , MDA le els we e 29% lowe , while a he 48 h hou , hey we e
10% highe compa ed wi h he con ol. Al hough di e ences wi h he con ol we e gene ally no signi ican , MDA le els
a he 12 h hou we e signi ican ly highe (p < 0.05). Compa isons ac oss ime poin s showed signi ican di e ences
be ween he 4 h and 48 h hou s, as well as be ween he 8 h and 48 h hou s (p < 0.05) (Figu e 4).
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Figu e 4 Change in MDA amoun o e ime acco ding o expe imen al g oups
4. Discussion
The p ima y mechanism o issue inju y caused by eac i e oxygen species (ROS) is lipid pe oxida ion o cell
memb anes. While lipid pe oxida ion occu s a e y low le els in heal hy issues, i s inc ease can be conside ed an
indica o o ROS-media ed issue damage. One o he deg ada ion p oduc s o lipid pe oxida ion is malondialdehyde
(MDA), and he measu emen o MDA le els is widely accep ed as a bioma ke o in i o ROS-media ed inju y [21].
In his s udy, he e ec s o coenzyme Q10 (CoQ), an an ioxidan , and cyclic adenosine monophospha e (cAMP), a
seconda y messenge egula ing a ious cellula unc ions, we e in es iga ed in a cispla in (Cis)-induced hepa o oxici y
model. Speci ically, we examined hei impac on hepa ic adical-sca enging enzyme ac i i ies and MDA o ma ion.
Ou esul s demons a ed ha Cis adminis a ion al e ed SOD, CAT, and GPx ac i i ies and inc eased MDA le els.
Tü kmen e al. [22] epo ed ha in a Cis-induced ca dio oxici y model, ac i i ies o SOD, GPx, CAT, and o al glu a hione
le els dec eased signi ican ly. Simila ly, Taghizadeh [23] showed ha MDA le els, hepa ic inju y enzymes (ALT, AST,
ALP), and caspase-3 immuno eac i i y inc eased in he li e issue o Cis-injec ed mice. Doğan e al. [24] also epo ed
ha Cis ma kedly ele a ed MDA and 8-OHdG le els in kidney and li e issues.
In ou s udy, adminis a ion o CoQ alone signi ican ly educed MDA le els a all ime poin s. When CoQ was co-
adminis e ed wi h Cis, i a enua ed Cis-induced MDA ele a ion, pa icula ly a he 8 h and 48 h hou s. Suna [25]
demons a ed ha CoQ supplemen a ion supp essed MDA p oduc ion, he eby p e en ing Cis-induced
his opa hological e inal inju y. Ho mozi e al. [26] also showed ha CoQ e ec i ely educed MDA le els and imp o ed
an ioxidan enzyme ac i i y in cadmium-exposed a li e s.
Ou indings indica e ha Cis igge s ime-dependen dynamic changes in an ioxidan enzyme ac i i ies. SOD and CAT
inhibi ion in he ea ly phase (4–8 h), ollowed by eac i a ion a 12–24 h, e lec s an adap i e s ess esponse in
hepa ocy es. Simila ly, he ma ked GPx inc ease a 24–48 h is consis en wi h a la e-phase ac i a ion o he NRF2-ARE
pa hway, a c i ical de ense axis agains oxida i e s ess [27]. These da a suppo he no ion ha di e en bioma ke s
a y in hei sensi i i y and iming in esponse o oxida i e inju y [5]. The inc ease in MDA le els obse ed in ou s udy
also sugges s ha Cis no only induces classical oxida i e s ess bu may also igge e op osis, a lipid pe oxida ion–
d i en o m o p og ammed cell dea h. P e ious s udies emphasized he c i ical ole o GPx4 and he NRF2 pa hway in
e op osis egula ion, highligh ing GPx ac i i y as an adap i e esponse o supp ess e op osis [4,27].
One o he mos impo an indings o ou s udy is ha cAMP demons a ed an ioxidan e ec s compa able o CoQ.
Pa icula ly in he ea ly phase (4–12 h), cAMP adminis a ion signi ican ly educed MDA le els and modula ed SOD and
CAT ac i i ies. These esul s can be explained by he ac i a ion o he cAMP/CREB signaling pa hway, which induces
an ioxidan gene exp ession and supp esses in lamma ion. In line wi h ou indings, se e al s udies ha e epo ed ha
ele a ion o in acellula cAMP a enua es oxida i e s ess and in lamma ion while imp o ing mi ochond ial unc ions,
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he eby exe ing hepa op o ec i e e ec s [9,10,29,30]. Al hough CoQ p o ided a mo e s able and sus ained an ioxidan
esponse, he ea ly p o ec i e e ec o cAMP sugges s ha i may ep esen a aluable he apeu ic candida e agains
Cis-induced hepa o oxici y.
CoQ ea men consis en ly supp essed MDA le els and imp o ed an ioxidan enzyme ac i i ies a all examined ime
poin s. This is in ag eemen wi h p e ious epo s showing he p o ec i e e ec s o CoQ agains oxida i e s ess–
media ed damage in mul iple issues, including he e ina, kidney, and li e [8,25,26]. Fu he mo e, s udies ha e
sugges ed ha CoQ exe s syne gis ic an ioxidan e ec s when combined wi h o he agen s [28]. The enhanced la e-
phase hepa op o ec ion obse ed in he cAMP+CoQ g oup in ou s udy u he suppo s he he apeu ic po en ial o
combina ion s a egies.
Finally, ecen s udies ha e demons a ed ha ER s ess and ac i a ion o he PERK/ATF4/CHOP axis play impo an
oles in Cis-induced hepa o oxici y [2,6]. The educ ion in MDA le els and imp o emen in an ioxidan enzyme ac i i ies
obse ed in ou s udy may be associa ed wi h alle ia ion o hese s ess esponses. Taken oge he , ou indings
highligh ha bo h cAMP and CoQ mi iga e Cis-induced hepa o oxici y h ough mul iple mechanisms, including
modula ion o oxida i e s ess, e op osis, and ER s ess pa hways.
Ou s udy demons a ed ha cispla in induces ime-dependen oxida i e s ess in he li e , du ing which di e en
componen s o he an ioxidan de ense sys em a e ac i a ed a dis inc ime in e als. The indings e ealed ha SOD
and CAT ac i i ies we e supp essed in he ea ly phase, whe eas GPx ac i i y was ma kedly inc eased in he la e phase.
This obse a ion is consis en wi h he dynamic ac i a ion pa e ns o he NRF2-ARE pa hway desc ibed in he li e a u e
[27]. Mo eo e , he inc ease in MDA le els sugges s ha cispla in may igge no only classical oxida i e s ess bu also
lipid pe oxida ion–d i en cell dea h pa hways ( e op osis) [4].
Wi h espec o pha macological in e en ions, cAMP adminis a ion signi ican ly educed MDA le els and modula ed
SOD and CAT ac i i ies. These indings a e in line wi h cu en e idence indica ing ha he cAMP/CREB pa hway
supp esses oxida i e s ess and in lamma ion [9,10,29,30]. CoQ adminis a ion, on he o he hand, consis en ly
dec eased MDA le els and imp o ed an ioxidan enzyme ac i i ies. This ou come pa allels p e ious s udies epo ing
he p o ec i e e ec s o CoQ agains oxida i e s ess–media ed damage in a ious issues [7,8,25,26].
Ano he no ewo hy inding was he syne gis ic e ec obse ed wi h he combined adminis a ion o cAMP and CoQ.
This combina ion pa icula ly enhanced GPx ac i i y in he la e phase and exe ed he mos p onounced supp ession o
MDA le els. Such esul s a e consis en wi h ecen li e a u e highligh ing he he apeu ic po en ial o an ioxidan
combina ion s a egies [28].
5. Conclusion
This s udy demons a ed ha cispla in induces ime-dependen oxida i e s ess in he li e , du ing which di e en
componen s o he an ioxidan de ense sys em a e ac i a ed a dis inc ime in e als. The indings e ealed ha SOD
and CAT ac i i ies we e supp essed in he ea ly phase, whe eas GPx ac i i y was ma kedly inc eased in he la e phase.
Fu he mo e, he ele a ion o MDA le els indica ed ha cispla in igge s no only classical oxida i e s ess bu also
lipid pe oxida ion–d i en cell dea h pa hways ( e op osis).
In conclusion, he da a ob ained demons a e ha in he cispla in-induced hepa o oxici y model, cAMP exhibi s
an ioxidan e ec s compa able o hose o CoQ, wi h bo h agen s p o iding signi ican p o ec i e oles. No ably, hei
combined adminis a ion achie ed he g ea es bene i by supp essing oxida i e s ess and enhancing an ioxidan
de ense. These indings highligh he po en ial o cAMP and CoQ as p omising candida es o he de elopmen o no el
neu op o ec i e and an icance adju an s a egies aimed a mi iga ing cispla in-associa ed hepa o oxici y.
Compliance wi h e hical s anda ds
Disclosu e o con lic o in e es
No con lic o in e es o be disclosed.
GSC Biological and Pha maceu ical Sciences, 2025, 32(03), 223-231
230
S a emen o e hical app o al
This s udy was app o ed by he Ondokuz Mayıs Uni e si y Animal E hics Commi ee decision numbe ed HEK/28.
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