This study investigated the potential uroprotective effects of pomegranate on cyclophosphamide-induced hemorrhagic cystitis in rats. Rats were divided into four groups - one control group, one group given cyclophosphamide only, one group given cyclophosphamide and Mesna, and one group given cyclophosphamide and a pomegranate diet. Urodynamic studies and histopathological analysis found that the mean detrusor pressure and histological damage were significantly lower in the pomegranate group compared to the other groups, indicating that pomegranate may help reduce the severity of cyclophosphamide-induced hemorrhagic cystitis through its antioxidant and anti-inflammatory properties.

1. Assessment of uroprotective effects of pomegranate in
cyclophosphamide induced hemorrhagic cystitis: an
experimental study in rats
N Mahmoudi, M Golmohammadi ,S Eftekharzadeh, R Khorramirouz, Z Kashani, M
Alijani , AM Kajbafzadeh
Pediatric Urology and Regenative Medicine Research Center, Section of Tissue
Engineering and Stem Cell Therapy, Pediatric Center of Excellence, Tehran University of
Medical Sciences, Tehran, Iran (IRI)
INTRODUCTION
High antioxidant properties of pomegranate as well as
its anti-inflammatory effects can be beneficial in
prevention and alleviation of cyclophosphamide-
induced Hemorrhagic Cystitis (HC), a fatal yet
unpredictable and poor managed phenomenon. We aim
to investigate effect of Dietary Pomegranate extracts
and juice on alleviating HC episodes.
RESULTS
Analysis of urodynamic findings revealed that mean
detrusor pressure in Group 4(24.50±7.18cmH2O) was
significantly lower comparing to both positive control
group and group 3(43.25±3.59 and 27.75±8.42cmH2O
respectively, p value<0.05). Mean end-fill pressure in
group 4(17.00±7.74) was also lower comparing to
group 2 and group 3(14.75±1.89ml/cmH2O
and10.00±4.96ml/cmH2O), but it was not statistically
significant. Histopathological characteristics of
cyclophosphamide-induced HC including edema,
vascular dilation and hemorrhage, Degeneration,
desquamation and destruction of urothelium were
markedly decreased in rats of group 4.
Fig. 1: Hemorrhagic cystitis model in a rat with
hemorrhagic vessels
METHODS
Sixteen Sprague–Dawley rats were divided into 4
groups: Group 1 was the negative control group
(sham). In the other 3 groups HC was induced by
intraperitoneal administration of a single dose of
cyclophosphamide (150 mg/kg). Rats of Group 2 were
the positive control receiving only cyclophosphamide.
In group 3 rats received Mesna (2-mercaptoethane
sulfonate sodium) with a dose of 30 mg/kg suspended
in 2 ml of N/S in 3 separate doses (30 minutes prior to
cyclophosphamide injection, one dose after 4 hours
and the last dose after 8 hours). Rats in Group 4 have
been receiving a 14-day special diet consisting of
Pomegranate juice plus peel extracts (2 cc/day) prior
to HC induction. Urodynamic studies were performed
in all rats 48 hours after HC induction..
Fig2:. Hematoxylin and eosin staining of control,
cyclophosphamide, cyclophosphamide-Mesna and
cyclophosphamide-Pomegranate groups.
DISCUSSION & CONCLUSIONS
Hematopoietic cell transplantation recipients who
receive cyclophosphamide as part of their
conditioning regimen might benefit from
Administration of pomegranate-derived antioxidants
along with Mesna to decrease severity of HC and its
sequels.
Fig.3. Masson Trichrome staining of control,
cyclophosphamide, cyclophosphamide-Mesna and
cyclophosphamide-Pomegranate groups.
Fig.4. Picrosirius staining of control, cyclophosphamide,
cyclophosphamide-Mesna and cyclophosphamide-
Pomegranate groups.
P366