Pediatric Urology
Inflammation and Oxidative
Stress in Testicular Torsion:
Do They Deserve Intensive Treatment
to Save Both Guilty and Innocent Testes?
Serhat Gürocak, Akin Yilmaz, Ebru Alp, Iyimser U
¨
re, Sinan Sözen, Sevda Menevs ¸e,
Adnan Menevs ¸e, and Ibrahim Bozkirli
OBJECTIVES To investigate at the molecular level, whether the combined use of an antioxidant (L-carnitine)
and a selective cyclooxygenase-2 (COX-2) inhibitor (meloxicam) is effective in the treatment of
cellular damage caused by testicular torsion.
METHODS A total of 30 male Wistar rats were randomly divided into 5 groups. The control group
underwent a sham operation, and the second group underwent torsion/detorsion for 90 minutes.
Groups 3 and 4 received L-carnitine (500 mg/kg/d) and meloxicam (3 mg/kg/d), respectively.
Group 5 also received these 2 agents, in addition to the same torsion/detorsion procedure.
Bilateral orchiectomy was performed 96 hours after the operation in all groups. cDNA was
synthesized after isolation of total RNA from the tissues. The relative expression of interleukin
(IL)-1a, COX-2, and -actin genes was measured by real-time polymerase chain reaction.
RESULTS The COX-2 and IL-1a mRNA levels had significantly decreased in groups 3, 4, and 5 compared
with group 2 (P .05). COX-2 and IL-1a mRNA levels were significantly great in the
torsion/detorsion group (P = .007). The COX-2 and IL-1a mRNA levels significantly decreased
in the torsion/detorsion testis after maximal treatment (P .001).
CONCLUSIONS Meloxicam seems to exert its inhibitory effect on the expression of specific genes of inflammation, as
well as the combination therapy. Because the effects of these inflammatory genes are still evident 4
days after detorsion, combination therapy using these agents could be administered until late
postoperative period to prevent the initiation of autoimmune activity against sperm cells and protect
the innocent contralateral testis from the insult of antisperm antibodies. UROLOGY 78: 164 –169,
2011. © 2011 Elsevier Inc.
T
esticular torsion is considered a urologic emer-
gency that occurs mostly in adolescent and
younger males.
1
Its incidence is 1 in 158 males by
the age of 24 years and approximately 1 in 4000 annu-
ally.
2
The testicular torsion and detorsion process causes
ischemia-reperfusion (I-R) damage on the testis. The
pathophysiologic mechanisms are mainly the direct dam-
age caused by ischemia during torsion and the secondary
effect of reperfusion that occurs during the untwisting of
the spermatic cord. If the restoration of testicular flow to
the ischemic testis is essential for tissue preservation,
organ reperfusion could even have harmful effects.
3
This
injury starts a pathophysiologic cascade, including acti-
vation of cytokines, which are the main mediators of
inflammation, and the generation of nitric oxide and
other reactive oxygen species.
4
Nonsteroidal anti-inflammatory drugs (NSAIDs) are
frequently used in the treatment of many diseases asso-
ciated with inflammation. The major mechanism of these
drugs is thought to be the inhibition of cyclooxygenase
(COX), the main enzyme of the inflammation process.
Meloxicam is a NSAID that is a specific inhibitor of the
COX-2 enzyme.
5
COX catalyzes the conversion of ara-
chidonic acid to prostaglandins G
2
and H
2
, the cytokines
contributing to the inflammation process.
6
The standard treatment of testicular torsion is surgical
detorsion. However, despite successful detorsion, because
of the I-R injury, apoptosis can remain in testicular tissue,
leading to germ cell damage and, finally, to male infer-
tility.
7
Abnormal semen results have been noted in 40%
to 60% of patients after unilateral testicular torsion.
8
To achieve a better salvage rate, surgical exploration
must be performed within 6 hours after the onset of
From the Department of Urology, Gazi University School of Medicine, Ankara,
Turkey; and Department of Medical Biology and Genetics, Gazi University School of
Medicine, Ankara, Turkey
Reprint requests: I
˙
yimser U
¨
re, M.D., Department of Urology, Gazi University
School of Medicine, Ankara, Turkey. E-mail: iyimserure@yahoo.com
Submitted: May 12, 2010, accepted (with revisions): December 12, 2010
164 © 2011 Elsevier Inc. 0090-4295/11/$36.00
All Rights Reserved doi:10.1016/j.urology.2010.12.069