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Among reactive oxygen species generated by human neutrophils during inflammatory disorders, hypochlorous acid and hydroxyl radical are especially involved in many diseases such as arteriosclerosis or emphysema. It was shown in vitro that two thiol-containing drugs, mesna and N-acetylcysteine, have antioxidant properties towards these oxidants. The 50% inhibitory concentrations (IC50s) of mesna and N-acetylcysteine for hypochlorous acid production by stimulated neutrophils were 29 and 30 mcM, respectively, and for hydroxyl radical production, IC50s were 520 and 480 mcM, respectively. With this in vitro demonstrated effectiveness, both mesna and N-acetylcysteine have been considered as therapeutic antioxidants to decrease tissue damage inflicted by an excess of activated neutrophils by scavenging hypochlorous acid and hydroxyl radical.

During inflammatory disorders, potentially destructive reactive oxygen species, especially hydrogen peroxide, are produced by activated phagocytic cells. It was demonstrated in vitro that mesna and N-acetylcysteine (NAC), mucolytic thiols, have antioxidant properties. An estimation was made of the 50% inhibitory concentration (IC50) of mesna and NAC for PMA-induced H2O2 production by human neutrophils, the results being 70 mcM and 77 mcM, respectively. The mechanism which governs mesna and NAC reactions results from a scavenging effect of H2O2: the calculated IC50s of this effect were 30 mcM and 42 mcM, respectively, in free cellular experimentation. The results suggest that mesna and NAC might be used as antioxidants in aerosols to prevent tissue damage inflicted by this reactive oxygen species, especially in the lungs.

2-Mercaptoethanesulfonate (Mesna), which is used as a uroprotective agent during oxazaphosphorine treatment, was previously found to inhibit growth of several tumor cell lines in vitro. To test the possibility that this effect is due to the SH-group of mesna, other thiols have now been tested. It has been observed that L-cysteine, N-acetyl-L-cysteine and glutathione, on a molar basis, had effects similar to mesna on [3H]thymidine incorporations of several human tumor cell lines in vitro. The dose-response profiles were monophasic for some cell lines and biphasic for others. It is suggested that compounds with SH-groups, in relatively high concentrations, may be toxic for cells.

Unlike "conventional" oxazaphosphorines such as cyclophosphamide (CP) and ifosfamide, a relatively new drug termed 4-hydroperoxy-CP (4-HC) degrades spontaneously in water yielding phosphoramide mustard considered to be the activated cytotoxic metabolite. During this degradation a toxic, volatile factor termed acrolein is also formed. In order to examine the possible role of this compound in 4-HC-induced inhibition of tumor cell growth in vitro, 8 different established human tumor cell lines were cultured in the presence of 4-HC or equimolar concentrations of acrolein. It was observed that the cell lines differed widely with respect to sensitivity to these compounds. However, each individual cell line exhibited virtually identical sensitivities to both 4-HC and acrolein. The observation that 2-mercaptoethansulfonate (mesna), which is highly reactive with acrolein but not with phosphoramide mustard, could markedly reduce the cytotoxic activity of 4-HC indicates that acrolein may play an important role in 4-HC induced cell damage in vitro.

2-Mercaptoethanesulfonate (mesna), which is used as an uroprotector during oxazaphosphorine therapy of cancer patients, was found to inhibit growth of several cultured human malignant cell lines in vitro. Dimesna, which is rapidly formed in the blood of mesna treated patients, had no effect and did not interfere with the growth inhibitory activity of mesna. For sensitive cell lines, complete growth inhibitions were usually observed at mesna concentrations of 10(-4) M. Higher concentrations were less toxic or even stimulated proliferation of some cell lines. There was no experimental evidence that the biphasic dose-response profiles were due to a more complete dimesna formation at high mesna concentrations. Since mesna, which is excreted in its monomeric form in urine, was reported to inhibit growth of superficial bladder cancer in patients, we examined the effects of repeated mesna administrations in cultures of bladder cancer cells. The results showed that this treatment caused growth inhibition of 2/4 "resistant" cell lines. The mechanisms by which mesna inhibits cell growth are unknown and it is not known if it acts selectively on malignant cells.