An in vitro model of renal inflammation after ischemic oxidative stress injury: nephroprotective effects of a hyaluronan ester with butyric acid on mesangial cells

Abstract

BackgroundAcute kidney injury, known as a major trigger for organ fibrosis and independent predictor of chronic kidney disease, is characterized by mesangial cell proliferation, inflammation and unbalance between biosynthesis and degradation of extracellular matrix. Therapeutic approaches targeting the inhibition of mesangial cell proliferation and matrix expansion may represent a promising opportunity for the treatment of kidney injury. An ester of hyaluronic acid and butyric acid (HB) has shown vasculogenic and regenerative properties in renal ischemic-damaged tissues, resulting in enhanced function recovery and minor degree of inflammation in vivo. This study evaluated the effect of HB treatment in mesangial cell cultures exposed to H2O2-induced oxidative stress.Materials and methodsLactate dehydrogenase release and caspase-3 activation were measured using mesangial cells prepared from rat kidneys to assess necrosis and apoptosis. Akt and p38 phosphorylation was analyzed to identify the possible mechanism underlying cell response to HB treatment. The relative expressions of matrix metallopeptidase 9 (MPP-9) and collagen type 1 alpha genes were also analyzed by quantitative real-time polymerase chain reaction. Cell proliferation rate and viability were measured using thiazolyl blue assay and flow cytometry analysis of cell cycle with propidium iodide.ResultsHB treatment promoted apoptosis of mesangial cells after H2O2-induced damage, decreased cellular proliferation and activated p38 pathway, increasing expression of its target gene MPP-9.ConclusionThis in vitro model shows that HB treatment seems to redirect mesangial cells toward apoptosis after oxidative damage and to reduce cell proliferation through p38 MAPK pathway activation and upregulation of MPP-9 gene expression involved in mesangial matrix remodeling.

The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

“…Our study showed that renal I/R was associated with a significant increase in cardiac Bax protein value compared to the control group and this was in agreement with others (Liu et al, 2007). Previous studies suggested that oxidative stress and subsequent inflammation have an important role in magnifying the apoptosis in the ischemic organ and distant organ damages (Baraldi et al, 2017). In our study, lithium tetraborate could ameliorate myocardial apoptosis via positive regulation of antioxidant defense and negative regulation of inflammation/oxidative stress signaling pathways.…”

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

“…With sodium butyrate administered as a preventative measure, myeloperoxidase activity and entry of inflammatory cells into the lungs are markedly reduced, and these effects are linked to the suppression of proinflammatory cytokines (TNF-alpha and IL-6), HMGB1 expression, and NF-κB activation (Figure ). Sodium butyrate and propionate target the lipopolysaccharide (LPS)-related TLR-4/NF-κB pathway and reduce lung damage caused by LPS stimulated cytokines (including IL-6 and IL-12p40. − After being exposed to oxidative stress, hyaluronan ester plus butyric acid therapy promotes apoptosis in mesangial cells, inhibiting cell proliferation via the p38 MAPK pathway . The production of IL-13 and IL-15 by type 2 ILCs is inhibited by butyrate.…”

“… 167 − 169 After being exposed to oxidative stress, hyaluronan ester plus butyric acid therapy promotes apoptosis in mesangial cells, inhibiting cell proliferation via the p38 MAPK pathway. 170 The production of IL-13 and IL-15 by type 2 ILCs is inhibited by butyrate. Furthermore, butyrate suppresses the expression of inflammatory genes post-transcriptionally by downregulating a number of RNA binding proteins.…”

Is butyrate a natural alternative to dexamethasone in the management of CoVID-19?

“…The TLR 4/NF-κB pathway involved in the LPS is targeted by sodium butyrate, which attenuates the LPS induced lung injury 27 . Hyaluronan ester with butyric acid treatment induces apoptosis in mesangial cells after exposure to oxidative stress and thereby reducing cell proliferation via p38 MAPK pathway 141 . N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA), a butyrate releasing compound, confers protection to mice from colitis induced by dextran sodium sulphate by suppressing neutrophils recruitment and subsequent release of pro-inflammatory molecules mediated by HDAC-9/NF-κB inhibition and peroxisome proliferator-activated receptor gamma (PPAR-γ) upregulation 142 .…”