الفهرس 
Hemorrhagic cystitis definition:
Animal model of chemotherapy induced HCOnly 14 pages are availabe for public view
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Abstract
Hemorrhagic cystitis (HC) is defined as an inflammation of urinary bladder and urothelial damage. It is multifaceted disease with a complex of urinary dysfunctional manifestations which include lower urinary tract infection symptoms: (dysuria, urinary urgency, urinary frequency, and suprapubic pain) up to urinary retention and sever hematuria. HC is an acute serious pathology as it is a leading cause of hematuria. HC is a multicausal disease. It may be due to iatrogenic cause, secondary to viral infection and idiopathic, but iatrogenic etiology is the most predictable. The iatrogenic cause is due to chemotherapy or radiation exposure. Oxaphosphorines (cyclophosphamide, ifosfamide) are the chemotheraputic agents that are responsible for HC. HC diagnosis mainly depends on medical history and physical examination, but it should be confirmed by urine analysis that is negative for bacteria to exclude infectious cystitis. Urine analysis usually shows hematuria. Cystoscopy may show bleeding and friable urinary bladder mucosa. Computed tomography (CT) imaging may show increased density of the posterior wall of the urinary bladder reflecting blood clot formation. Prevalence of cyclophosphamide (CP) induced HC is 20-25% and the prevalence may reach up to 68% in patients who don’t receive Mesna as a prophylactic treatment. Besides, 75% of patients treated with high dose of CP may suffer HC. The pathogenesis of HC usually includes inflammatory reaction of urothelium, increased capillary permeability, edema, urothelial erosion, ulceration, necrosis and fibrosis. It also includes damage of detrusor muscle, urothelial innervation and superficial desquamation of urothelium that leads to impaired bladder permeability and irritation of sensory neurons by urine constituents that initiates action potential to spinal cord generating painful sensation. The pathogenesis of CP induced HC can be summarized in four stages; Acrolein invasion into uroepithelium yield to uroepithelial damage which is considered as a first stage. The second stage is inflammatory phase. In this phase there is increase in transcription factors such as nuclear factor kappaB (NF-κB) with subsequent increase in inflammatory cytokines e.g., tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL- 1β) and other proteins e.g. cyclooxygenase 2 (COX-2). The third stage is a symptomatic appearance that is associated with urothelial ulceration and yields to visceral pain. The fourth stage is a healing phase that includes tissue repair through fibroblasts and releasing of growth factors as keratinocyte growth factor. TNF-α regulates cytokines synthesis and more activation of NFKB. It also has an important role in induction of cell proliferation, differentiation, necrosis, and apoptosis. The oxidative stress can also promote apoptosis. As it increases the mitochondrial permeability yields to cytochrome c release to the cytosol consequence activation of caspases cascade. Besides, CP can decrease occludin protein in tight junctions of the urothelium leading to disturbance of urothelium permeability. Recently, there is a mounting proof that the autophagy has an important role in CP induced HC which is a cytoprotective mechanism and defined as a cellular reflex to stress exposure leading to double membrane autophagosomes formation and fusion with the lysosomes yielding to autolysosomes formation and subsequent degradation of damaged organelles.