Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice / Efectos Renoprotectores Sinérgicos del Extracto de Té Verde y Gemigliptina contra la Nefrotoxicidad Inducida por Tacrolimus en Ratones

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

Association between indication for therapy by nutrition support team and nutritional status.

The nutrition support team is a multidisciplinary team composed of medical doctors, registered nurses, pharmacists, and nutritionists, who evaluate the nutritional status of patients. The objective of this study was to determine the relationship between indications for nutrition support team therapy and the nutritional status of patients hospitalized in local major hospitals.Patients who were referred to a nutrition support team from January to December 2016 were enrolled. Patients were classified into 4 age groups, and the weight categories were determined using body mass index (BMI). Four of 6 indications were used for referral to a nutrition support team. The required calories were estimated, and the nutritional status was classified into malnutrition or eutrophia, based on the estimation.The proportion of elderly patients (37.0%) was higher than that of younger ones (28.3%). Patients with higher BMI had a relatively lower proportion of malnutrition. Patients receiving enteral nutrition had greater risk of malnutrition (adjusted odds ratio [aOR] = 3.77, 95% confidence interval [CI] = 2.71-5.24). Patients receiving parenteral nutrition (aOR = 0.38, 95% CI = 0.30-0.47) and treated in the intensive care unit (aOR = 0.70, 95% CI = 0.54-0.91) had lower risk of malnutrition. Patients with >3 indications for nutrition support team therapy had a lower risk of malnutrition than those with only 1 indication (aOR = 0.54, 95% CI = 0.37-0.77).Parenteral nutrition was the most common indication for referral to nutrition support team therapy; however, enteral nutrition had the poorest nutritional status. Patients receiving enteral nutrition who are referred to a nutrition support team need an intensive nutrition support strategy.

The effect of intravenous ascorbic acid in hemodialysis patients with normoferritinemic anemia.

BACKGROUND: Hemodialysis (HD) patients with functional iron deficiency often develop resistance to recombinant human erythropoietin (rhEPO). Recent studies have shown that intravenous ascorbic acid (IVAA) administration could override rhEPO resistance in HD patients. This study was undertaken to test the effects of IVAA in HD patients with normoferritinemic functional iron deficiency accompanied by EPO-hyporesponsive anemia. METHODS: Fifty-eight HD patients with normoferritinemic anemia (between 100 and 500 µg/L) were included and divided into the control (N=25) and IVAA (N=33) groups. IVAA patients received 500 mg of IVAA with each dialysis session for 3 months and an additional 4-month follow-up after the end of the therapy. RESULTS: Twenty patients had a response to IVAA with a significant increase in hemoglobin level (Hgb>1.0 g/dL) and reduction of weekly rhEPO dosage compared with the control group after 3 months of treatment (P<0.05). Compared with non-responders, transferrin saturation (TSAT) was significantly decreased in the responders group (26±11 vs. 35±14%, P<0.05) on baseline data. There was a significant increase in serum iron and TSAT (baseline vs. 3 months, serum iron 57±22 vs. 108±22 µg/dL, TSAT 26±11 vs. 52±7%, P<0.05) and a decrease in serum ferritin (377±146 vs. 233±145 ng/mL, P<0.05) in the responders group (N=20), but no significant changes in the control and non-responders groups (N=13) at 3-month treatment. CONCLUSION: IVAA can be a potent and effective adjuvant therapy for HD patients with rhEPO-resistant normoferritinemic anemia. In addition, IVAA can reduce the dosage of rhEPO for anemia correction.

Renoprotective effects of green tea extract on renin-angiotensin-aldosterone system in chronic cyclosporine-treated rats.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) activation plays an important role in cyclosporine (CsA)-induced nephropathy. The main aim of this study was to test whether the administration of green tea extract (GTE) prevents the development of CsA-induced nephrotoxicity. METHODS: The rats were treated for 21 days and divided into four groups (n = 6/group): control group (0.9% saline injection), CsA group (30 mg/kg/day by intraperitoneal injection), CsA-GTE group (CsA plus GTE 100 mg/kg/day subcutaneous injection) and GTE group (GTE alone). RESULTS: There were significant increased levels of serum blood urea nitrogen and creatinine in the CsA group compared with that of the control group and significantly improved in the CsA-GTE group. Biochemical analysis showed that the plasma renin activity (PRA) and serum concentration of aldosterone were significantly increased in the CsA group compared with the control group and significantly decreased in the CsA-GTE group compared with the CsA group. The total level of renin protein expression was significantly higher in the CsA group than in the control group, and it was lower in the CsA-GTE group than in the CsA group. CONCLUSIONS: CsA treatment increases the PRA and intrarenal renin levels and induces nephrotoxicity. The protective effects of GTE on CsA-induced structural and functional alternations of the kidney may be the blockage of RAAS.

The protective effects of green tea extract against L-arginine toxicity to cultured human mesangial cells.

The aim of this study was to investigate whether green tea extract (GTE) has the protective effects on excess L-arginine induced toxicity in human mesangial cell. Human mesangial cells treated with L-arginine were cultured on Dulbecco's modified eagle medium in the presence and absence of inducible nitric oxide synthase (iNOS) inhibitor and GTE. The cell proliferation was determined by 3 (4,5-dimethylthiazol-2-yl)-2, 5-diphengltetrqzolium bromide, a tetrazole assay. The iNOS mRNA and its protein expression were detected by reverse transcription polymerase chain reaction and Western blot, respectively. The concentration of nitric oxide (NO) was measured by NO enzyme-linced immuno sorbent assay kit. L-arginine significantly inhibited the proliferation of human mesangial cells, and induced the secretion of NO to the media. NO production by L-arginine was significantly suppressed by GTE and iNOS inhibitor (p<0.01). The expression level of iNOS mRNA and its protein that was significantly increased by L-arginine was decreased by iNOS inhibitor but not by GTE. GTE protected the mesangial cells from the NO-mediated cytotoxicity by scavenging the NO rather than by iNOS gene expression. Therefore, we conclude that GTE has some protective effect for renal cells against oxidative injury possibly by polyphenols contained in GTE.

Effects of Korean traditional herbal remedy on heart rate variability: linear and nonlinear analysis.

Heart rate variability was compared in 20 subjects taking traditional herbal remedy (Ondamtanggamibang) or placebo control pill, in placebo controlled design experiment. Herbal remedy group reported more pleasant and clam emotions than did the placebo group. Herbal remedy reduced the heart rate and increased heart rate variability (HRV) as indicated by a reduced low frequency/high frequency power ratio of heart rate variability. With nonlinear analysis, the Poincaré plot index of HRV and approximate entropy was greater in the herbal remedy group than in the control group. These findings suggest that herbal remedy stabilizes the sympathovagal function and cardiac autonomic nervous system by inducing more positive emotions than does placebo therapy. In conclusion, herbal remedy may act by stabilizing both the autonomic nervous system and the emotional state.

Hydrodynamic analysis of waveforms induced by vibrational stimuli at meridian and non-meridian points.

Meridian theory is an important part of traditional Chinese medicine (TCM). Although acupuncture has been accepted in many countries, the nature of the meridian theory and the principles of acupuncture are still unclear in the modern scientific view. The purpose of this study was to determine the differences in wave propagation of mechanical vibrations (optimal stimulator frequency of 40 Hz) through the pericardium meridian [EH-4 (Chieh-Men) and EH-5 (Chien-Shih)] and adjacent control regions in 20 subjects using hydrodynamic analysis. The mean transfer speed was significantly lower in the meridian (4 m/s) than in the adjacent control region (8.5 m/s, P < 0.001). There were also significant differences between the meridian and control points in the attenuation rate (P < 0.001) and peak amplitude (P < 0.001). In conclusion, these results imply that the substance of the meridian differs from that of the adjacent control regions.