Date Published: October 14, 2019
Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em
Author(s): Antonio Carlos Cerqueira Oliveira, Norma Sueli Pinheiro Módolo, Maria Aparecida Custódio Domingues, Paulo Adriano Schwingel.
To assess Cyclosporine A (CsA) therapy at an intraperitoneal dose of 15 mg.kg
-1 in a rodent model of non-septic renal ischemia.
Twenty male Wistar rats were randomized to receive CsA therapy or none
therapy before undergoing 30 minutes of renal ischemia followed by
reperfusion. Additionally, 10 rats were randomized to undergo the same
surgical procedure of the aforementioned animals with neither ischemia nor
CsA therapy. Twelve hours after kidney ischemia, the left kidneys were
evaluated for histological injury according to Park’s criteria. Serum
creatinine (Cr), urea nitrogen (Ur) and sodium levels were obtained at
different times of the experimental protocol.
Rodents in the CsA group showed negative results (p<0.05) in serum variables (Cr: 0.41±0.05mg/dL vs . 4.17±1.25mg/dL; Ur: 40.90±3.98mg/dL vs . 187.70±22.93mg/dL) even the non CsA or control group (Cr: 0.35±0.07mg/dL vs . 3.80±1.20mg/dL; Ur: 40.10±4.70mg/dL vs . 184.50±49.80mg/dL). The negative results were also verified in histological evaluation, CsA group had 50% in the very severe grade of lesion, 10% in the severe and 40% in the moderate to severe whereas the control group had 90% in the very severe grade. CsA was incapable of preventing the deleterious effects of ischemia-reperfusion injury in rat kidneys.
Ischemic injuries in vital organs, such as the heart, brain and kidneys, can
decisively contribute to increased morbidity and mortality 1 , 2 . Renal ischemia during arterial occlusion, shock and organ transplantation
are commonly associated with cell death, renal failure, delayed graft function in
kidney transplantation and renal graft rejection 3 . Following an episode of acute renal ischemia, early reperfusion continues
to be a first-line strategy to limit damage caused to this organ. Nonetheless, renal
reperfusion per se has the potential to cause cellular death 4 , similarly to what has been observed in the heart 5 . An investigation of protective strategies utilized at the time of
reperfusion is fundamental to preventing this type of lesion 6 , 7 .
The present experimental study was conducted between March and June 2013. Our
research proposal received approval from the Animal Experimentation Institutional
Review Board (number 1034-2013, later modified by CEUA number 24/2015) to include 30
male Wistar rats weighing no less than 300 grams each, provided by the Central
Animal Care Facility. These animals were randomly divided by using a
computer-generated table of random number into three groups: Sham Group (SG),
submitted to laparotomy and right nephrectomy; Control Group (CG), also submitted to
laparotomy and right nephrectomy, in addition to ischemia-reperfusion of the left
kidney; and CsA Group (CsAG), submitted to the same procedures as the above groups,
and that additionally received intraperitoneal (IP) CsA at a dose of 15 mg.kg
-1 , in two different moments, 24 hours before and immediately
preceding the first surgical intervention.
The statistical analysis demonstrated that the mean weight of Wistar rats from CG
(458.0±50.5) was higher (p=0.002) than from CsAG animals (405.0±46.7), and then from
SG rodents (387.0±18.9). In addition, rats from CsAG and SG have similar mean
weights according to the Bonferroni’s post-hoc comparisons tests. One-way ANOVA
revealed that the rectal T of the animals and the SBP values were similar among all
three groups (p>0.05). On the other hand, MBP and DBP demonstrated statistical
differences between the groups according to post-hoc tests ( Table 4 ).
The present study aimed to evaluate the effects of CsA on ischemia-reperfusion injury
in rat kidneys. Our results indicated that the administration of this drug did not,
at the specified dosage and under the conditions described herein, prevent tissue
damage arising from ischemic injury following reperfusion. Despite the statistically
significant differences between rodents’ weight in the three groups, this parameter
did not interfere on the results from other studied variables, as all of them belong
to the same lineage and have the same degree of maturity. In addition, the
distribution between groups was by random draw.
CsA was unable to prevent the deleterious effects of ischemia-reperfusion injury in
rat kidneys under the conditions of the present study.