S-allyl cysteine ameliorates cyclophosphamide-induced downregulation of urothelial uroplakin IIIa with a concomitant effect on expression and release of CCL11 and TNF-α in mice

Background: The aim of this study was to evaluate the modulatory effect of S-allyl cysteine against cyclophosphamide-induced changes in uroplakin IIIa, CCL11 and TNF-alpha. Methods: Mice were treated with cyclophosphamide (200 mg/kg x 7 d, ip). S-allyl cysteine (150 mg/kg x 7d, ip), and comparator compound mesna (40 mg/kg x 7d, ip) were administered 1 h before and 4 h after each cyclophosphamide dose. The urinary bladder was analysed for mRNA and protein changes in uroplakin IIIa (UPIIIa), CCL11 and TNF-alpha and histopathological findings. Results: Cyclophosphamide caused hemorrhagic cystitis formation and downregulation of UPIIIa. These changes were accompanied by upregulation of CCL11 and TNF-alpha, S-allyl cysteine attenuated these changes including protection at histological level. Mesna which was used as a comparator drug also showed protection. However, relatively S-allyl cysteine showed a stronger protective effect than mesna. Conclusion: These findings highlight a correlation between downregulaion of UPIIIa and enhanced production of inflammatory biomarkers and protective effects of S-allyl cysteine which has been reported to be a potent uroprotective agent. The present study strengthens its role which could be clinically exploited in chemotherapy regimen. (C) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.