Comparision of uroprotective activity of reduced glutathione with Mesna in Ifosfamide induced hemorrhagic cystitis in rats

Abstract

Background:Ifosfamide (IFO) is widely used DNA-alkylating agents in cancer chemotherapy for management of solid tumors and hematological malignancies. However, hemorrhagic cystitis limits the use of IFO.Objectives:To compare the efficiency of reduced glutathione with 2-Mesna in reducing Ifosfamide (IFO) induced hemorrhagic cystitis (HC) in wistar rats.Materials and Methods:Ifosfamide and 2-Mesna were dissolved in sterile water for injection and administered to wistar rats of albino strains. The rats were randomly assigned to one of the four groups of 6 rats each: Group I: Vehicle control; Group II: 120 mg/kg of IFO alone by intraperitoneal injection (i.p); Group III: 40 mg/kg Mesna i.p., at the same time and at 4 and 8 h after IFO administration; Group IV: 500 mg/kg of glutathione i.p., 30 min prior to IFO as above. The animals were observed for 5 days. On 6th day, rats were sacrificed by dissecting the intrajugular vein. The bladders were macroscopically and histopathologically evaluated.Results:Control animals had normal bladders with assigned scores of ‘0’ for the three parameters of edema, hemorrhage and histopathological changes. All the animals receiving IFO (group II) had evidence of HC as evidenced by alterations of edema and hemorrhages. These alterations were almost abolished (P < 0.001) by the glutathione (group III) or Mesna (group IV) in IFO-treated animals.Conclusion:Glutathione could be as useful as Mesna in the preventive management of IFO-induced HC.

Review of Advances in Uroprotective Agents for Cyclophosphamide- and Ifosfamide-induced Hemorrhagic Cystitis

“…The authors concluded that glutathione has the potential to be at least as useful as mesna in patients being treated with ifosfamide. 30 The second article studied the effects of a single dose of ketamine combined with mesna in ifosfamide-exposed rats. These investigations showed that ketamine combined with mesna reduced bladder wet weight, and that ketamine alone prevents microscopic changes associated with hemorrhagic cystitis.…”

Hemorrhagic Cystitis With Low-Dose Cyclophosphamide Therapy for Breast Cancer: A Rare Occurrence

“…The sulfhydryl groups of mesna bind with the urotoxic elements of acrolein and prevent it from acting on the bladder wall [4,18]. The efficacy of mesna, especially in CP patients is controversial and HC still occurs in 10-40% of mesna-treated patients [19]. Liberal hydration before and several hours after administration of CP is recommended to prevent HC [4].…”