(R)-Lisofylline

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Background

Lisofylline (LSF) is a potent anti-inflammatory agent. LSF is a chiral metabolite of pentoxifylline. (R)-LSF is the biologically active isomer of LSF [1]. In vitro: Lisofylline preserved β-cell insulin secretion and inhibited DNA damage of islets in the presence of IL-1β [2]. Simultaneous application of LSF and cytokines to INS-1 cells restored insulin secretion, mitochondrial membrane potential, MTT metabolism, and cell viability to control levels. LSF increased β-cell MTT metabolism as well as insulin release and glucose responsiveness [3].In vivo: In rats subjected to hemorrhagic shock and resuscitation, LSF increased the intestinal and hepatic blood flow. Treatment with LSF (15 mg/kg) ameliorated the development of mucosal damage and hyperpermeability. Rats treated with LSF showed lower plasma concentrations of the intracellular hepatic enzyme, aspartate aminotransferase. LSF treatment increased concentrations of adenosine triphosphate in intestinal and hepatic tissue [1]. In NOD mice, lisofylline suppressed IFN-γ production, reduced the onset of insulitis and diabetes, and inhibited diabetes after transfer of splenocytes from Lisofylline-treated donors to NOD.scid recipients [2].

[1] Wattanasirichaigoon S, Menconi M J, Fink M P. Lisofylline ameliorates intestinal and hepatic injury induced by hemorrhage and resuscitation in rats[J]. Critical care medicine, 2000, 28(5): 1540-1549.
[2] Yang Z D, Chen M, Wu R, et al. The anti-inflammatory compound lisofylline prevents Type I diabetes in non-obese diabetic mice[J]. Diabetologia, 2002, 45(9): 1307-1314.
[3] Chen M, Yang Z, Wu R, et al. Lisofylline, a novel antiinflammatory agent, protects pancreatic β-cells from proinflammatory cytokine damage by promoting mitochondrial metabolism[J]. Endocrinology, 2002, 143(6): 2341-2348.