Alleviation of Cyclophosphamide-induced Hemorrhagic Cystitis by Dietary Pomegranate: A Comparative Experimental Study With Mesna

Abstract

In this study, we investigated the effects of pomegranate on alleviating cyclophosphamide-induced hemorrhagic cystitis (HC). Initially, 16 Sprague-Dawley rats were allocated into 4 groups: group 1 (control), group 2 (CP) in which HC was induced by cyclophosphamide; group 3 (CP+M), HC-induced rats that received Mesna regimen, and group 4 (CP+P), which compromised rats that had been on a 14-day diet of pomegranate juice before HC induction. Cystometry was performed a few hours before euthanasia; after euthanasia, aortic blood samples and bladder tissue samples were obtained to perform TUNEL assay, and histopathologic and biochemical assessments. Urodynamic findings revealed that mean detrusor pressure in CP+P was significantly lower compared with that in CP and CP+M (P<0.05). Histopathologically, urothelium destruction and inflammation were lower in CP+P and CP+M compared with that in CP. Collagen destruction was less prominent in CP+P compared with that in CP and CP+M. Tissue and plasma levels of malondialdehyde were significantly lower in CP+P versus CP (P<0.05). Catalase activity and total protein thiol group levels in plasma and bladder tissue were higher in CP+P versus CP (P<0.05). The TUNEL positivity in CP+P was significantly weaker than that in CP, indicating less DNA fragmentation and apoptosis. Pomegranate's characteristics could significantly affect the inflammatory and destructive process of hemorrhagic cystitis.

Effect of a Low Dose of Carvedilol on Cyclophosphamide-Induced Urinary Toxicity in Rats—A Comparison with Mesna

“…The addition of mesna in our experiment partly prevented CPX-induced changes in both parameters. This is consistent with other published data, in which mesna administration reversed the CPX-induced bladder edema [69,71]. Furthermore, in our study, mesna alone or combined with carvedilol completely reversed the hematuria measured semi-quantitatively on a dipstick test, but carvedilol alone has no hematuria-preventive action.…”

Potential Protective Effects of Mesna and Vitamin D Separately or Concomitantly on Cyclophosphamide Induced Hemorrhagic Cystitis in Rats

“…As Mesna is a sulfhydryl donor 61 , it can ameliorate CP induced HC. Our results confirmed this concept, as Mesna ameliorated the oxidative stress through a significant increase in TAC and a significant decrease in MDA level compared to the CP group which agrees with Mahmoudi et al, (2018) 62 . The preventive role of Mesna against HC is not restricted to its antioxidant effect but extends to antiinflammatory and anti-apoptotic effects63.…”

Uroprotective mechanisms of natural products against cyclophosphamide-induced urinary bladder toxicity: A comprehensive review

“…In animal models of CYP-induced urotoxicity, treatment with thymoquinone showed a marked reduced percentage in tail DNA content, length, and moment confirming its antiapoptotic uroprotective effect via inhibition of DNA fragmentation and damage (Gore et al, 2016). Furthermore, administration of pomegranate, a medicinal plant in Indian culture, and DADS exhibited a marked reduction in bladder TUNEL positive cells (Kim et al, 2014;Mahmoudi et al, 2018).…”