RESUMO
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.
RESUMO
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.
RESUMO
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.
