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Description of key information

MPS possesses uroprotective efficacy against ifosfamide induced haemorrhagic cystitis in rats at dose levels of 100 and 215 mg/kg bw. 

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Sodium-3-mercapto-propane sulfonate (Asta 7100 = MPS) was tested for its uroprotective efficacy in 5 Sprague Dawley rats treated with 68 mg/kg ifosfamide that is known to induce haemorrhagic cystitis (Brock et al., 1981). MPS was administered by i. v. administration 15 min before the injection of ifosfamide at the screening dose of 100 mg/kg bw and thereafter was raised or lowered in steps with a factor of 2.15. The dose levels were 21.5, 68.1 and 215 mg/kg bw. The uroprotective efficacy of MPS was evaluated 24 hours after the administration of ifosfamide. The rats were killed and the urinary bladders were evaluated (inflammation, bleeding and weight). The severity of the inflammation of the bladder after i.v. administration of ifosfamide was dose-dependent. An ifosfamide dose of 68 mg/kg always induced an approximately 2- fold increase in the wet weight of the bladder and a damage score of about 2. Some of the rats also showed bladder haemorrhages. The scoring system used takes into account two parameters: firstly, increased capillary permeability (which is demonstrable objectively by the extravasal occurrence of intravenously injected trypan blue) and secondly, the increase in the weight of the bladder, which can also be assessed macroscopically as a swelling of the bladder. In some selected groups the bladder damage and the extent of bladder protection were also investigated histologically. The uroprotective effect of MPS was dose-dependent. It was reflected in a reduced increase in the bladder weight and reduced extravasation of trypan blue, and it was also demonstrable histologically. MPS exerted its uroprotective effect at doses of 100 and 215 mg/kg bw. MPS was, however, less effective than its short-chain homologue mesna (CAS 19767 -45 -4).