ABSTRACT
Objective:To investigate the protective function and mechanism of β-hydroxybutyrate (β-HOB) on cisplatin (CP)-induced nephrotoxicity.Methods:C57BL/6 male mice aged 10 weeks were randomly divided into the following three groups: control group (no special treatment), β- HOB+CP group (mice received intraperitoneal injection of 20 mmol/kg β-HOB for 10 days), CP group (received intraperitoneal injection of normal saline for 10 days). CP group and β-HOB+CP group were given once cisplatin (20 mg/kg) intraperitoneal injection on the 8th day in the experiment. On the 10th day, all the mice were sacrificed. Renal pathology was evaluated by HE staining; blood samples were collected for blood urea nitrogen (BUN) and serum creatinine (Scr) measurement; immunohistochemistry staining was performed to detect the protein level of Caspase3, Cleaved-caspase3, mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) in renal tissues; Western blotting was used to detect the relative expression levels of p-MAPK/MAPK and p-NF-κB/NF-κB. In vitro experiment, HK-2 cells were set into three groups: control group, CP group, β-HOB+CP group, and β-HOB+CP+Sappanone A (Sap, MAPK-p38 activator) group. The expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 were tested by cell immunofluorescence. The cell apoptosis and mitochondrial membrane potential (MMP) were examined by flow cytometry. DNA damage was detected by TUNEL staining. Results:In vivo experiments, the renal pathological injury score, BUN and Scr in CP group were significantly higher than those in control group (all P<0.05), while renal pathological injury score, BUN and Scr in β-HOB+CP group were lower than those in CP group (all P<0.05). The protein expression levels of p-MAPK, p-NF-κB, Caspase3 and Cleaved-caspase3 in CP group were higher than those in control group, while these indexes in β-HOB+CP group were lower than those in CP group (all P<0.05). In vitro experiments, compared with CP group, the MMP was higher in β-HOB+CP group; the ratio of cell apoptosis, the expression of Caspase3, Cleaved-caspase3, p-MAPK and p-NF-κB, and the number of TUNEL staining positive cells were significantly lower (all P<0.05). Compared with β-HOB+CP group, the MMP in β-HOB+CP+Sap group was lower; the ratio of cell apoptosis, the expression of Caspase3 and Cleaved-caspase3, and the number of TUNEL staining positive cells were significantly higher (all P<0.05). Conclusions:β-HOB can alleviate the acute renal injury induced by cisplatin, which may be related to the reduction of apoptosis and inhibition of MAPK/NF-κB pathway.
ABSTRACT
A spinal cord injury is a serious disease, and there is currently no effective treatment. The inflammatory reactions start within a few hours after damages to spinal cord tissues and peak within a few days and they may continue for several years. Reducing the inflammatory response after the spinal cord injury is one of the important treatment strategies. Butyrate and β-hydroxybutyrate are two closely related substances. They have similar structures and differ in only one hydroxyl group. They have attracted widespread attention because of their good anti-inflammatory properties in many diseases. Recently it has been demonstrated that butyrate and β-hydroxybutyrate can inhibit the activity of the NF-κB / NLRP3 inflamma-some signaling pathway and reduce the expression of pro-inflammatory factors; or by enhancing the level of antioxidant molecules, it can reduce the inflammatory response after spinal cord injury. Therefore, butyrate and β-hydroxybutyrate may be promising treatments after a spinal cord injury. Here we review the structure and production of butyrate and β-hydroxybutyrate, the mechanism of anti-inflammatory effects in a spinal cord injury, and the treatment prospects, in order to provide theoretical references for researchers in this field.
ABSTRACT
Cyanobacteria have many unexploited potential for natural products with a huge variability in structure and biological activity. Under stress conditions they are reported to produce biopolymers like poly-β-hydroxybutyrate (PHB), which can be produced intracellularly.Cyanobacteria are capable of synthesizing small amount of poly-β-hydroxybutyrate (PHB) under nitrogen and phosphorous starvation conditions. High performance liquid chromatography (HPLC) analysis revealed that about percentage PHB of the cell dry weight (CDW) was accumulated under mixotrophic culture condition. However, Nile red stained cells showed the presence of large quantities of granules in the cell cytoplasm when viewed under fluorescent microscope. The qualitative observation was in contrast to the quantitative HPLC analysis which suggested that the fluorescent granules are PHB. Among the ten different isolates, three strains showed the accumulation of PHB. The amount of PHB produced after 10 days in the depleted conditions are 1.182 mg/l for spirulina, 2.322 mg/l for anabena and 3.741 mg/l. The maximum PHB producer was further studied in detail. The extracted polymer was compared with the authentic PHB and was confirmed to be PHB using FTIR analysis. The present study shows increased PHB accumulation in different species by nitrogen and phosphorous depleted condition and pH concentration in the growth media.
ABSTRACT
The clinical values of acetoacetate ( AcAA ) and β hydroxybutyrate ( βHBA ) determination in classification of type 1 and2 diabetes were explored. 102 normal control subjects,33 cases of type 1 diabetes, and 104cases of type 2 diabetes were enrolled. Serum AcAA, βHBA, fasting plasma glucose ( FPG), C-peptide, and insulin levels were measured. The results showed that serum AcAA, βHBA, total ketone tody (TKB) levels in the diabetic groups were significantly higher than those of the normal group( P＜0. 01 ). AcAA, βHBA, TKB levels in type 1diabetes were higher as compared with those of type 2 diabetes( P＜0.01 ). The AcAA, βHBA, and TKB levels were negatively related with C-peptide and insulin in diabetic patients( P＜0. 01 ). All the type 1 diabetic patient were found to have TKB and lower C-peptide levels. TKB positive and lower C-peptide in type 2 diabetes were found in 47% and 26% respectively. Receiver operating characteristic (ROC) curve suggested that the area under the ROC curve of type 1 and type 2 diabetes was 0.926. The optimal operating point of the total ketone body was 0. 532 mmol/L with higher sensitivity and specificity. Enzymatic determination of acetoacetate and β hydroxybutyrate seems to have important clinical values for classification of type 1 and 2 diabetes.