Dimethyl Fumarate Ameliorates Acute Pancreatitis in Rodent

OBJECTIVES: Pancreatitis is a complex inflammatory disorder, ranging from a mild attack, to severe and potentially fatal condition. Dimethyl Fumarate (DMF), a potent antioxidant and anti-inflammatory, has been used medicinally for decades. The purpose of this study was to test the hypothesis that treatment with DMF may ameliorate acute pancreatitis (AP) in a rodent model. METHODS: Rats were treated with DMF (25 mg/Kg)24 hours prior to AP induction with L-arginine (3 g/Kg). At 72 hours, the pancreas was processed for histology. Serum amylase, lactate dehydrogenase, pancreatic trypsin, and lipid peroxidation product (MDA) were evaluated. Key cytokines and chemokinesin the supernatant of LPS-stimulated splenocytes were also determined. RESULTS: Pancreases from DMF treated rats showed reductions in the severity of inflammatory cell infiltration, acinar damage, perilobar edema, and cell necrosis. This was associated with significantly lower amylase and MDA but not lactate dehydrogenase, or trypsin levels. The apoptotic pancreatic cells (cleaved caspase 3 positive) were significantly lower in the DMF-treated rats. LPS-stimulated splenocytes treated with DMF produced a significantly lower amount of key inflammatory mediators. CONCLUSION: Administration of DMF attenuates A Pin rats

Melatonin Membrane Receptors in Peripheral Tissues: Distribution and Functions

Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, reproductive and cardiovascular functions, modulation of skin pigmentation, hair growth, cancerogenesis, and aging. Melatonin receptor agonists and antagonists have an exciting future since they could define multiple mechanisms by which melatonin modulates the complexity of such a wide variety of physiological and pathological processes