Review: 2-Mercaptoethanol alteration of in vitro immune functions of species other than murine

Abstract

Descriptions that organosulfurs could alter biologically relevant cellular functions began some 40 years ago when cell mediated and humoral murine in vitro immune responses were reported to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds—2-mercaptoethanol (2-ME), dithiothreitol, glutathione, and L-cysteine; the most effective of the four was 2-ME. These findings triggered a plethora of reports defining 2-ME benefits for a multitude of immunological processes, primarily with murine models. This led to investigations on 2-ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in situ diseases. In addition, the early findings may have been instrumental in identification of the previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Outside the plant organosulfurs, there are no comprehensive reviews of these areas to help define mechanisms by which organosulfurs function as well as identify potential alternative uses. Therefore, the present review will focus on 2-ME alterations of in vitro immune functions in species other than murine; namely, fish, amphibian, reptile, avian, whales, dolphins, rat, hamster, rabbit, guinea pig, feline, canine, porcine, ovine, bovine, and human. Processes, some unique to a given species, were in general, enhanced and in some cases dependent upon the presence of 2-ME. The largest benefits occurred in media that were serum free, followed by those in autologous serum and then fetal bovine serum supplemented medium. Concentrations of 2-ME were generally in the low μM range, with exceptions of those for salamander (20 mM), turtles (70 mM) and dolphins (7 mM). The few studies designed to assess mechanisms found that changes induced by 2-ME were generally accompanied by alterations of reduced/oxidized glutathione cellular concentrations. The major benefit for most studies, however, was to increase the sensitivity of the culture environment, which permitted a specific process to be more easily dissected.

Thiosulfoxide (Sulfane) Sulfur: New Chemistry and New Regulatory Roles in Biology

“…Aside from their absolute requirement in the MTAP- and CTH-defective cells, these precursors of sulfane sulfur have dramatic effects in increasing the viability, health, vigor, and proliferative capacity of many cell types in vitro . Today, MER, TGL, or TEA are routinely added to many in vitro cell systems involving immune cells, hematopoietic cells, reproductive cells, embryonic cells, and stem cells [ 29 , 30 , 31 ]. These sulfane precursor compounds are added at μM concentrations and, by integration of kinetic parameters, it can be shown that the concentration of sulfane sulfur in the media at any time is in the nanomolar (nM) range [ 17 ].…”

“…The fact that these sulfane chains are present in the “H 2 S” test systems supports the conclusion that the active agent is sulfane sulfur rather than hydrogen sulfide. It should be noted that the proposed agents (thiophosphates and dithiolethiones) are less appropriate as “therapeutic” agents than are mercaptoethanol disulfide and cystamine, which have already been tested in animals [ 29 , 30 , 31 ].…”

“…This increased vigor could indirectly increase the cellular content of oxygen-defensive factors such as glutathione, catalase, and superoxide dismutase. Numerous reports have described an increase in cellular glutathione in the presence of sulfur compounds related to sulfane sulfur [ 29 , 30 , 31 , 45 , 54 ]. The presence of air-exposed solutions of NaHS has been shown to increase the expression of Mn-SOD in ischemia-stressed cardiomyocytes as well as the in vitro activity of CuZn SOD [ 103 ].…”

A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

“…These findings were soon confirmed and extended [ 8 , 9 , 10 , 11 , 12 , 13 ] which led to a plethora of reports defining thiol benefits for many different immunological processes. This extensive literature stimulated investigations of 2ME, other xenobiotic and food derived organosulfurs on other cell-types, other species, non-immune processes, inactivation of carcinogens and cancer control [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The evidence leaves little doubt that many different xenobiotic and plant derived organosulfurs have an impact on an enormous number of biological processes.…”

“…The enormity of the seemingly unrelated processes and diseases that are altered precludes a coherent single review. To this end, articles on (a) plant derived anticarcinogenic organosulfurs [ 16 , 17 ], (b) preventive and therapeutic value of 2ME and other small xenobiotic organosulfurs for cancers induced by different etiologic agents [ 18 , 19 ], and (c) alteration of in vitro immune processes of species other than murine [ 20 ] are available. The present review of in vitro fertilization processes altered by thiols was undertaken with two major questions in mind.…”