Effect of 3-mercaptopyruvate sulfurtransferase deficiency on the development of multiorgan failure, inflammation, and wound healing in mice subjected to burn injury

The gaseous transmitter hydrogen sulfide (H 2 S) has been implicated in various forms of critical illness. Here, we have compared the outcome of scald burn injury in wild-Type mice and in mice deficient in 3-mercaptopyruvate sulfurtransferase (3-MST), a mammalian H 2 S-generating enzyme. Outcome variables included indices of organ injury, clinical chemistry parameters, and plasma levels of inflammatory mediators. Plasma levels of H 2 S significantly increased in response to burn in wild-Type mice, but remained unchanged in 3-MST-/-mice. The capacity of tissue homogenates to produce H 2 S from 3-mercaptopyruvate was unaffected by burn injury. In 3-MST-/-mice, compared to wild-Type controls, there was a significant enhancement in the accumulation of polymorphonuclear cells (as assessed by the quantification of myeloperoxidase) in the liver (but not heart, lung, or skin) at 7 days postburn. Oxidative tissue damage (as assessed by malon dialdehyde content) was comparable between wild-Type and 3-MST-deficient mice in all tissues studied. 3-MST-/-and wild-Type mice exhibited comparable burn-induced elevations in circulating plasma levels of hepatic injury; however, 3-MST-/-mice exhibited a higher degree of renal injury (as reflected by elevated blood urea nitrogen levels) at 7 days postburn. Inflammatory mediators (eg, TNF-α, IL-1β, IL-2, IL-6, IL-10, and IL-12) increased in burn injury, but without significant differences between the 3-MST-/-and wild-Type groups. The healing of the burn wound was also unaffected by 3-MST deficiency. In conclusion, the absence of the H 2 S-producing enzyme 3-MST slightly exacerbates the development of multiorgan dysfunction but does not affect inflammatory mediator production or wound healing in a murine model of burn injury.