Modulation by Taurine of the Toxicity of Taumustine, a Compound With Antitumor Activity2

Abstract

The antitumor activity of 2-[bis-(2-chloroethyl)-amino]ethanesulfonic acid (also referred to here as "taurine mustard" or "taumustine") was evaluated in the murine P388 and L1210 lymphocytic leukemias and in the pigmented and nonpigmented B16 melanoma systems. Treatment with a single ip dose of taumustine (40 mg/kg) resulted in a 130% increase in life-span for mice bearing P388 (intraperitoneal), a 93% increase for mice bearing L1210 (intraperitoneal), and an approximately 80% increase for mice bearing B16 melanoma (intraperitoneal). Repeated low doses (10 mg/kg) of taumustine promoted a 250% increase in life-span for mice bearing P388 (intraperitoneal), the absence of ascitic fluid from day 4 onward, and the presence of pulmonary emboli from day 5 onward. The inclusion of taurine (5 mM) in the culture medium of P388 cells in primary culture for 45 hours did not alter the cytotoxicity of taumustine, and pretreatment of the tumor-bearing host with taurine (250 mg/kg) in daily treatments with taumustine for up to 8 days did not interfere with antitumor activity (140-160% increased life-span). However, treatment of tumor-bearing mice with taurine abrogated neurotoxicity, intestinal necrosis, pulmonary emboli formation, and tail vein necrosis due to the administration of taumustine. The modulation by taurine of taumustine activity suggests that the combination of these agents offers an advantage of selectivity and host protection during chemotherapy.

Physiological actions of taurine

“…The taurine derivative taumustine, or Z-bis-(Zchloroethyl)aminoethane sulfonic acid, is an antitumor agent having a number of toxic side effects. Taurine does not affect the antitumor action but decreases the neurotoxicity and pulmonary embolism associated with taumustine (623). Both these phenomena are Ca2' related.…”

Pharmacokinetics of Oral Taurine in Healthy Volunteers

“…Obinata et al showed ALT concentrations recovering in children with fatty liver after 6-months treatment with oral taurine administered daily [4]. Protective effects of taurine against arteriosclerosis [5], lung injury by oxidant gases [6], deleterious effects of various drugs such as tauromustine, an antitumor agent, [7], hepatotoxicity of sulfolithocholate [8], and its promotion of the recovery of leukocytes in irradiated rats [9] have already been studied on animals. The therapeutic effects of taurine on epilepsy [10], ischemia [11], obesity [12], diabetes [13], hypertension [14], Congestive heart failure [15], noxious effect of smoking [16], toxicity of methotrexate [17] myocardial infarction [18], alcoholic craving [19], and neurodegeneration in elderly [20] have also been reported.…”

Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

“…Such antidote effects of taurine or high capacity for taurine uptake into the cells (or conversely harmful effects of taurine depletion) have i.a . been found against alcohol (23–40), against the analgesic and fever-depressing drug acetaminophen (also called paracetamol) (41–44), against the aminoglycoside antibacterial drug gentamicin (45–47), against the immunosuppressant drug cyclosporine A (48, 49), against the anticancer drugs cisplatin (50–54), doxorubicin (also called adriamycin) (55–62), bleomycin (63–78), methotrexate (79) and taumustine (80), against the cytokine interleukin-2 (IL-2), which is used for immunotherapy of cancer (81–84), against the estrogen receptor modulator tamoxifen, which is used in therapy of breast cancer (85–87), against the antiarrhythmic drug amiodarone (88), against the beta -adrenergic agonists isoproterenol (55) and isoprenaline (89–92), against nicotine (93–95), against oxidized low-density lipoprotein (LDL) (96), against oxidized fish oil (97), against high glucose levels (96, 98–110), against fructose (111–122), against galactose (123), against advanced glycation end-products (AGEs) (100, 124, 125), against homocysteine (126–130), against the anti-inflammatory drugs ibuprofen (131) and indomethacin (132, 133), against the herbicide paraquat (65, 134, 135), against carbon tetrachloride (136–149), against menadione (150), against 1,4-naphtoquinone (137, 139), against hydrazine (137, 139), against trinitrobenzene sulfonic acid (151, 152), against acrylonitrile (153), against perchloroethylene (154), against methylene dianiline (155), against arsenic (156–164), against cadmium (…”