Protective Effects of S-Adenosylmethionine and Its Combinations With Taurine and/or Betaine Against Lipopolysaccharide or Polyinosinic-polycytidylic Acid-induced Acute Hepatotoxicity

Abstract

BackgroundSeveral mechanisms for the pathogenesis of many liver diseases are related with oxidative stress, endotoxins, and infections by many microorganisms. These can lead to chronic hepatitis, cirrhosis, and even liver cancer. The aim of this study was to evaluate the effects of S-adenosylmethionine (SAMe) and its combinations with taurine and/or betaine against hepatotoxicites induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (polyI:C).MethodsRAW 264.7 macrophage cells and seven-week-old male C57BL/6 mice were pretreated with SAMe (SAM or AdoMet), taurine, and/or betaine. In order to mimic hepatic injury like endotoxemia or viral infection, cells and mice were treated with LPS or polyI:C. Concentrations of glutathione (GSH), mRNA expressions of GSH synthesizing enzymes, and inflammatory markers were measured by biochemical assays and quantitative real-time PCR.ResultsIn RAW 264.7 cells and mice, pretreatment of SAMe alone or SAMe with taurine and/or betaine attenuated the decrease in GSH levels and mRNA expressions of GSH synthesizing enzymes. In addition, pretreatment of SAMe with taurine and/or betaine prevented the excessive increase in inflammatory mediators produced by LPS or polyI:C treatment.ConclusionsTreatment with SAMe in combination with taurine and betaine, would have anti-oxidant functions in addition to anti-inflammatory action against bacterial and/or viral inflammation.

Temporal changes in glutathione biosynthesis during the lipopolysaccharide-induced inflammatory response of THP-1 macrophages

“…As GCL is the rate-limiting enzyme for the de novo synthesis of GSH and its expression was reportedly decreased by LPS [13, 25], we hypothesized that the temporal change of GSH content in the inflammatory response observed above was due to alteration of GCL expression. To test it, the mRNA and protein levels of both GCLC and GCLM, the two subunits of GCL, were determined in THP1 macrophages exposed to 10 ng/ml LPS for various time periods.…”

“…It was postulated that the decrease was due to the deficiency of precursor amino acids for GSH synthesis such as cysteine [29, 30] or the increased consumption of GSH during inflammation [10-14]. Accumulating evidence indicate that the decrease in GSH level in LPS-triggered inflammatory response might be largely attributed to the decrease in GCL expression [13, 25]. The current finding that the decrease in the intracellular GSH occurred coincidentally with the decrease in GCLC expression (protein and mRNA) level in the early phase of the inflammatory response (Fig.…”

“…It has been reported that both GSH concentration and the expression level of GCL were decreased in the inflammatory response of inflammatory cells including macrophages [12, 13, 25]. This however, is inconsistent with the well-established finding that GCL expression is induced (increased) in response to oxidative stress.…”

Farmaconutrición: ¿El fin de una era?

“…Los aminoácidos azufrados (AAz) y sus metabolitos principales tienen un papel fundamental en los sistemas antioxidantes celulares y atenúan los síntomas proinflamatorios. En una investigación muy interesante presentada en la Sociedad de Nutrición Parenteral y Enteral de Asia PENSA 2018, Kwang Suk Ko en la Universidad de Ewha Womans, Corea (9) añadió AAz en macrófagos deficientes en prohibitin-1 seguido de la activación de lipopolisacáridos (LPS). La prohibitin-1 (una chaperona mitocondrial y un gen supresor de tumores hepáticos) agravó la respuesta inflamatoria de los macrófagos, mientras que los AAz atenuaron esos efectos adversos en comparación con los controles.…”

S-Adenosylmethionine in the Treatment of Experimental Hepatic Encephalopathy

“…SАМ в виде монопрепарата или в комбинации с другими гепатопртекторами оказывает выраженный терапевтический эффект при остром поражении печени, вызванном различными факторами, однако без явных признаков нейротоксичности [9][10][11].…”