Mesna partially protects the liver against CCl 4-hepatotoxicity in rats

Abstract

Of the large number of thiols and other thio compounds which were tested in this connection, only a few possess the chemical, pharmacological and pharmacokinetic properties required for successful regional protection of the kidneys and urinary bladder against the urotoxicity of oxazaphosphorine cytostatics. Sodium -2-mercapto-ethane sulfonate (INN: Mesna, Uromitexan®) far excels all the other compounds tested with regard to uroprotective efficacy, low intrinsic toxicity, favorable pharmacokinetics and absence of systemic interactions with oxazaphosphorines. With correctly timed administration of mesna it is possible to completely obviate regionally the urotoxicity of oxazaphosphorines, which often constitutes a therapy-limiting factor, without impairing the therapeutically desirable systemically mediated oncotoxic effects of these drugs. Amongst the compounds tested in this connection, a few further compounds were also found to possess uroprotective efficacy, but only in high doses. Their therapeutic range is so narrow that toxic complications are likely to arise in clinical use. Thio-amino acids, for example, show a modest uroprotective effect only in very high, sub-toxic doses. The mechanism of the uroprotective efficacy of mesna is based on the formation of non-toxic compounds with the 4-hydroxy metabolites of oxazaphosphorines and with the acrolein which is formed in the urine from 4-hydroxy-oxazaphosphorines.