Blood Serum Metabolite and Volatile Fatty Acid Profiles of Finishing Pigs Fed Diets with High and Low Levels of Energy and Crude Protein

Background: Studying how dietary imbalances affect blood serum metabolite (BSM) and faecal volatile fatty acids (VFA) profiles may help to understand whether pigs are fed adequate diets in commercial farms. The present study aimed to evaluate the effect of high and low net energy (NE) and crude protein (CP) diets on performance, BSM and VFA profiles on finishing pigs.Results: Twenty pens of 11 pigs (87.0 ± 4.10 kg; 18 weeks old) were assigned to 1 out of 5 dietary treatments (DT): control (C; 10.03 MJ/kg NE, 160.0 g/kg CP, and 9.5 g/kg SID Lys), low CP (LCP; 10.03 MJ/kg NE, 132.0 g/kg CP, 7.5 g/kg SID Lys), high CP (HCP; 10.03 MJ/kg NE, 188.0 g/kg CP, 11.5 g/kg SID Lys), low NE (LNE; 9.61 MJ/kg NE, 160.0 g/kg CP, 9.5 g/kg SID Lys) and high NE (HNE; 10.45 MJ/kg NE, 160.0 g/kg CP, 9.5 g/kg SID Lys). Pigs were followed for 10 days and blood and faecal samples were collected at the end of the trial. Performance was not affected by DT (P > 0.05). Albumin and glucose did not differ between DT (P > 0.05). HNE pigs had higher triglycerides (0.42 ± 0.03 mmol/L) and creatinine (133.8 ± 3.97 µmol/L) than LNE pigs (0.28 ± 0.03; 117.2 ± 3.97; P < 0.05); however, HNE pigs had lower total protein (60.9 ± 1.51 g/L) than C pigs (67.4 ± 1.51; P = 0.033). LCP pigs had higher cholesterol (2.4 ± 0.08 mmol/L) than LNE pigs (2.0 ± 0.08; P = 0.015); while HCP pigs had higher serum urea nitrogen (13.6 ± 0.95 mg/dL) than the other DT (7.5 ± 0.95; P < 0.001). Total VFA (mmol/kg) did not differ among DT (P > 0.05), but C and HNE pigs had higher branched-chain fatty acids (6.3 ± 0.38% of total VFA) than LNE pigs (4.4 ± 0.38; P < 0.05).Conclusions: Dietary imbalances in energy and protein affect BSM and VFA profile. BSM and VFA analysis may be good indicators to detect unbalanced diets in pig farms, especially serum urea nitrogen, to detect an excess of protein.

Dehydroxymethylepoxyquinomicin, a novel nuclear factor-kB inhibitor, prevents the development of cyclosporine A nephrotoxicity in a rat model

Background: Cyclosporine A (CsA) is an essential immunosuppressant in organ transplantation. However, its chronic nephrotoxicity is an obstacle to long allograft survival that has not been overcome. Nuclear factor-kB (NF-kB) is activated in the renal tissue in CsA nephropathy. In this study, we aimed to investigate the effect of the specific NF-kB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), in a rat model of CsA nephrotoxicity. Methods: We administered CsA (15 mg/kg) daily for 28 days to Sprague-Dawley rats that underwent 5/6 nephrectomy under a low-salt diet. We administered DHMEQ (8 mg/kg) simultaneously with CsA to the treatment group, daily for 28 days and evaluated its effect on CsA nephrotoxicity. Results: DHMEQ significantly inhibited NF-kB activation and nuclear translocation due to CsA treatment. Elevated serum urea nitrogen and creatinine levels due to repeated CsA administration were significantly decreased by DHMEQ treatment (serum urea nitrogen in CsA + DHMEQ vs CsA vs control, 69 ± 6.4 vs 113.5 ± 8.8 vs 43.1 ± 1.1 mg/dL, respectively, p < 0.0001; serum creatinine in CsA + DHMEQ vs CsA vs control, 0.75 ± 0.02 vs 0.91 ± 0.02 vs 0.49 ± 0.02 mg/dL, respectively, p < 0.0001), and creatinine clearance was restored in the treatment group (CsA + DHMEQ vs CsA vs control, 2.57 ± 0.09 vs 1.94 ± 0.12 vs 4.61 ± 0.18 ml/min/kg, respectively, p < 0.0001). However, DHMEQ treatment did not alter the inhibitory effect of CsA on urinary protein secretion. The development of renal fibrosis due to chronic CsA nephrotoxicity was significantly inhibited by DHMEQ treatment (CsA + DHMEQ vs CsA vs control, 13.4 ± 7.1 vs 35.6 ± 18.4 vs 9.4 ± 5.4%, respectively, p < 0.0001), and these results reflected the results of renal functional assessment. DHMEQ treatment also had an inhibitory effect on the increased expression of chemokines, monocyte chemoattractant protein-1, and chemokine (c-c motif) ligand 5 due to repeated CsA administration, which inhibited the infiltration of macrophages and neutrophils into the renal tissue.Conclusions: These findings suggest that DHMEQ treatment in combination therapy with CsA-based immunosuppression is beneficial to prevent the development of CsA-induced nephrotoxicity.

Dehydroxymethylepoxyquinomicin, a novel nuclear factor-κB inhibitor, prevents the development of cyclosporine A nephrotoxicity in a rat model

Background Cyclosporine A (CsA) is an essential immunosuppressant in organ transplantation. However, its chronic nephrotoxicity is an obstacle to long allograft survival that has not been overcome. Nuclear factor-kB (NF-kB) is activated in the renal tissue in CsA nephropathy. In this study, we aimed to investigate the effect of the specific NF-kB activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) in a rat model of CsA nephrotoxicity. Methods We administered CsA (15 mg/kg) daily for 28 days to Sprague-Dawley rats that underwent 5/6 nephrectomy under a low-salt diet. We administered DHMEQ (8 mg/kg) simultaneously with CsA to the treatment group, daily for 28 days and evaluated its effect on CsA nephrotoxicity. Results DHMEQ significantly inhibited NF-kB activation and nuclear translocation due to CsA treatment. Elevated serum urea nitrogen and creatinine levels due to repeated CsA administration were significantly decreased by DHMEQ treatment (serum urea nitrogen in CsA + DHMEQ vs CsA vs control, 69 ± 6.4 vs 113.5 ± 8.8 mg/dL vs 43.1 ± 1.1, respectively, p < 0.0001; serum creatinine in CsA + DHMEQ vs CsA vs control, 0.75 ± 0.02 vs 0.91 ± 0.02 vs 0.49 ± 0.02 mg/dL, respectively, p < 0.0001), and creatinine clearance was restored in the treatment group (CsA + DHMEQ vs CsA vs control, 2.57 ± 0.09 vs 1.94 ± 0.12 vs 4.61 ± 0.18 ml/min/kg, respectively, p < 0.0001). However, DHMEQ treatment did not alter the inhibitory effect of CsA on urinary protein secretion. The development of renal fibrosis due to chronic CsA nephrotoxicity was significantly inhibited by DHMEQ treatment (CsA + DHMEQ vs CsA vs control, 13.4 ± 7.1 vs 35.6 ±18.4 vs 9.4 ± 5.4%, respectively, p < 0.0001), and these results reflected the results of renal functional assessment. DHMEQ treatment also had an inhibitory effect on the increased expression of chemokines, monocyte chemoattractant protein-1, and chemokine (c-c motif) ligand 5 due to repeated CsA administration, which inhibited the infiltration of macrophages and neutrophils into the renal tissue. Conclusions These findings suggest that DHMEQ treatment in combination therapy with CsA-based immunosuppression is beneficial to prevent the development of CsA-induced nephrotoxicity.

Equidistant combination wavelength screening and step-by-step phase-out method for the near-infrared spectroscopic analysis of serum urea nitrogen

We applied near-infrared (NIR) spectroscopy with chemometrics for the rapid and reagent-free analysis of serum urea nitrogen (SUN). The modeling is based on the average effect of multiple sample partitions to achieve parameter selection with stability. A multiparameter optimization platform with Norris derivative filter–partial least squares (Norris-PLS) was developed to select the most suitable mode [Formula: see text], [Formula: see text], [Formula: see text]. Using equidistant combination PLS (EC-PLS) with four parameters (initial wavelength [Formula: see text], number of wavelengths [Formula: see text], number of wavelength gaps [Formula: see text] and latent variables LV), we performed wavelength screening after eliminating high-absorption wavebands. The optimal EC-PLS parameters were [Formula: see text][Formula: see text]nm, [Formula: see text], [Formula: see text] and [Formula: see text]. The root-mean-square error (SEP), correlation coefficient [Formula: see text] for prediction and ratio of performance-to-deviation (RPD) for validation were 1.03[Formula: see text]mmol[Formula: see text]L[Formula: see text], 0.992 and 7.6, respectively. We proposed the wavelength step-by-step phase-out PLS (WSP-PLS) to remove redundant wavelengths in the top 100 EC-PLS models with improved prediction performance. The combination of 19 wavelengths was identified as the optimal model for SUN. The SEP, [Formula: see text] and RPD in validation were 1.01[Formula: see text]mmol[Formula: see text]L[Formula: see text], 0.992 and 7.7, respectively. The prediction effect and wavelength complexity were better than those of EC-PLS. Our results showed that NIR spectroscopy combined with the EC-PLS and WSP-PLS methods enabled the high-precision analysis of SUN. WSP-PLS is a secondary optimization method that can further optimize any wavelength model obtained through other continuous or discrete strategies to establish a simple and better model.