Role of oxidative and nitrosative stress in cisplatin cardiotoxicity
Entry
Cisplatin, bladder, head and neck,
solid organ such as lung, testis and ovary
used in the treatment of tumors
It is an effective chemotherapeutic.1 Major side effects
effects include nephrotoxicity,
neurotoxicity and myelosuppression.
Although these side effects
use and anticancer efficacy
the most serious and dose-limiting
Although nephrotoxicity2, in recent years
during the use of cisplatin in studies and
development of cardiotoxicity
raised as an important problem
has arrived.
3-5
As a primary treatment for cisplatin
A major problem of acute cardiotoxicity
as well as chemotherapy
clinical signs that occur during
toxic cardiac effects
results appear years later.
6 20 from cisplatin treatment
still detectable in circulation, even after years
level of cisplatin; it's late
considered responsible for the complication
has been done.
7. Therefore also
possibility of causing cardiotoxicity
in the use of drugs with high
prevent cardiotoxicity as early as possible.
It is important to determine.
Secondary to cisplatin chemotherapy
observable cardiac pathologies
failure, angina, acute myocardial infarction,
thromboembolic events, hypertension,
hypotension, myocarditis, pericarditis,
It can be considered as congestive cardiomyopathy.
As the cause of these pathologies; vascular
endothelial damage, coronary vasospasm, oxidative
and nitrosative stress in platelet functions.
disruption, platelet apoptosis, platelet
aggregation, fluid electrolyte imbalance,
ventricular repolarization, mitochondrial
abnormalities and increased endoplasmic
reticulum stress is shown.
5 all this
oxidative and nitrosative factors
stress is a particular focus.
3
Currently on cisplatin
against toxic effects
an approved treatment that can be used
protocol and a specific antidote
not found8, still heavily
anti-toxicity strategies
is being investigated. In its pathogenesis, oxidative
and nitrosative stress
Considering the benefits of using antioxidants
lays out.
Therefore, in this study, with cisplatin
of cardiotoxicity
used for years in the clinic for the prevention of
serious side effects even at high doses
NAC 9, a powerful antioxidant
effectiveness has been studied.
Method
Erciyes University Scientific
by the Research Projects Commission
supported (Project no: TTU-2015-6134) and
Erciyes University Faculty of Medicine Ethics
Approved by the Board (dated 10/12/2014,
decision no:14/168) this study is in Erciyes
It was held at the University.
During the study, 12 hours
on a light/dark cycle, normal room
rats kept at temperature (22±1ºC) and humidity,
with standard pellet feed and tap water
fed. To adapt to the environment
for the purpose of; rats, at least before starting the study
It was taken into the same experimental environment a week ago.
The study included eight rats each.
four groups were created: Control (KONT),
cisplatin (CP), NAC-250 and CP+ NAC group.
Cisplatin10 and
Literature information and preliminary data on NAC11 doses
study results (data not shown)
decided in the light of
The first application to the control group
saline twice a day, four hours apart
(SF) injection was given and two consecutive days
It was continued with a single dose of SF. to the CP group
at a dose of 10 mg/kg rat weight on the first day
cisplatin (Cisplatin DBL®, 100 mg/ 100 mL)
while the other injection
Only SF application was made at the time.
250 mg/kg for three days in NAC-250 group
rat weight NAC (Asist®, Bilim Pharmaceuticals 300 mg/ 3
mL, 10%) was applied. To the CP+NAC group
on the first day of the study, first a single dose of 10 mg/kg
rat weight dose of cisplatin; two agents
cisplatin to minimize its interaction
at the fourth hour of its application12 and
250 mg/kg rat weight for two more consecutive days
dose of NAC was applied