Danshen modulates Nrf2-mediated signaling pathway in cisplatin-induced renal injury.

Danshen, an efficacious agent for cardiovascular diseases, has been found to play an essential role in kidney injury. In the present study, the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment. A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity. The mice were sacrificed 72 h after cisplatin intoxication. Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed. Histopathological changes of kidney tissues were detected using HE staining. Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected. Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting. The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice. Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin. Moreover, Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues. Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice. It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice, which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

Danshen Modulates Nrf2-mediated Signaling Pathway in Cisplatin-induced Renal Injury / 华中科技大学学报（医学）（英德文版）

Danshen,an efficacious agent for cardiovascular diseases,has been found to play an essential role in kidney injury.In the present study,the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model.Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment.A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity.The mice were sacrificed 72 h after cisplatin intoxication.Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed.Histopathological changes of kidney tissues were detected using HE staining.Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected.Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting.The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice.Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin.Moreover,Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues.Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice.It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice,which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

The influence of mutant lactobacilli on serum creatinine and urea nitrogen concentrations and renal pathology in 5/6 nephrectomized rats.

OBJECTIVES: To explore the capacity of mutant lactobacilli to remove creatinine (Cr) and urea nitrogen (UN) via the gastrointestinal tract and its effects on renal pathology in the 5/6 nephrectomized rat model of chronic renal failure. METHODS: Sixty Sprague-Dawley rats were randomly divided into a Sham group, a Model group, a wide-type Lactobacilli group (L.B group), and a Mutant Lactobacilli group (Mut-L.B group). The rats in the Model, LB and Mut-L.B groups underwent 5/6 nephrectomy. Eight weeks after administration, 24-h urine, orbital blood and digestive secretions were collected to analyze Cr and UN levels. Pathological changes in nephridial tissues were observed by hematoxylin and eosin and Masson trichrome staining, and the expression of TGF-ß1 and FN was detected by immunohistochemistry. RESULTS: There were no significant differences in urinary Cr and UN levels among the Sham, L.B and Mut-L.B groups (p > .05), while serum and digestive Cr and UN levels were significantly decreased in the Mut-L.B group (p < .01). Furthermore, renal tubular injury and interstitial fibrosis were significantly reduced and TGF-ß1 and FN expression was decreased (p < .05) in the Mut-L.B group. CONCLUSION: Mutant lactobacilli decreased serum Cr and UN levels, reduced the expression of TGF-ß1 and FN in renal tissues and alleviated renal interstitial injury and fibrosis in a rat model of chronic renal failure in a mechanism that may involve decomposition and not just excretion of small molecule toxins in the gastrointestinal tract.

Lactobacillus bulgaricus mutants decompose uremic toxins.

BACKGROUND/AIMS: We aim to obtain a probiotic strain from Lactobacillus bulgaricus by testing its capability to decompose uremic toxins to provide new intestinal bacteria for the treatment of chronic renal failure. METHODS: Original L. bulgaricus was cultured with the serum of uremic patients and then mutated by physical (ultraviolet) and chemical (diethyl sulfate) methods repeatedly. Using creatinine decomposition rate as an observed index, we selected the best strains which decreased the most concentration of the creatinine. We then tested its ability to decompose urea, uric acid, serum phosphate, parathyroid hormone, and homocysteine and its genetic stability. RESULTS: After inductive and mutagenic treatment, DUC3-17 was selected. Its decomposition rate of creatinine, urea nitrogen, uric acid, phosphorus, parathyroid hormone, and homocysteine were 17.23%, 36.02%, 9.84%, 15.73%, 78.26%, and 12.69%, respectively. The degrading capacity was sustained over five generations. CONCLUSIONS: After directional induction and compound mutation, L. bulgaricus has greater capacity to decompose uremic toxins, with a stable inheritance.

Shenfushu granule and atropine attenuate microvasculature loss in rat models with 5/6 nephrectomy.

OBJECTIVE: To investigate the effect of Shenfushu granule (SFSG) and atropine treatment on microvessels of the kidney and intestine after chronic renal failure (CRF) induced by 5/6 nephrectomy. METHODS: Sprague Dawley rats were randomly divided into a sham group, a model group, an SFSG group, and an SFSG + atropine group. SFSG was administered daily 1 week after inducing CRF. Rats were sacrificed at the end of the eighth week. Urinary protein and stool and serum urea nitrogen (UN) and creatinine (Cr) levels were assessed. Hematoxylin and eosin and periodic acid-Schiff staining of the kidney and examination of the vascular endothelial growth factor (VEGF) and microvessel density (MVD) levels in kidney and intestine were performed. RESULTS: The Cr and UN levels were significantly increased in blood and stool of the model group. SFSG significantly improved renal function, and the protective effects were further enhanced with the addition of atropine. Glomerular sclerosis, tubulointerstitial fibrosis, and microvessel loss were observed in CRF rats, and these pathological changes were ameliorated in the two treatment groups (p < 0.05), especially in the SFSG + atropine group. The expression of VEGF and MVD was decreased in the CRF rats compared with the sham group. SFSG treatment increased the expression of these proteins and reversed the degree of microvessel loss, glomerular sclerosis, and tubulointerstitial fibrosis (p < 0.05). Co-treatment with atropine enhanced these effects. CONCLUSIONS: SFSG alleviated renal function, upregulated the expression of VEGF and MVD in the kidney and intestine, and attenuated the degree of microvessel loss, glomerular sclerosis, and tubulointerstitial fibrosis in the early stages of CRF in rats, and addition of atropine enhanced these effects.

Isolation and characterization of polymorphic microsatellite loci in Camellia nitidissima Chi (Theaceae).

PREMISE OF THE STUDY: Microsatellite markers were developed in Camellia nitidissima for further population genetic studies. • METHODS AND RESULTS: Eight microsatellite markers were newly developed from C. nitidissima and 7 were transferred from other Camellia species. Two to 13 alleles per locus were identified for these microsatellites. Observed and expected heterozygosities ranged from 0.040 to 0.909, and 0.184 to 0.916, respectively. Four loci showed a significant deviation from Hardy-Weinberg equilibrium and five locus pairs displayed linkage disequilibrium. • CONCLUSIONS: These microsatellite markers will be useful to assess the genetic variation and genetic structure of C. nitidissima.

[Effect of potassium iodide on prevention of experimental lead nephropathy and expression of nuclear factor-kappaB and fibronectin].

OBJECTIVE: To investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin. METHODS: The experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR. RESULTS: Electron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F. CONCLUSION: The potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

[Effect of benazepril on the VEGF and MVD in the remnant kidney of 5/6 subtotal nephrectomized rats].

OBJECTIVE: To explore the effect of benazepril (one of angiotesin converting enzymes) on the expression of vascular endothelial growth factor (VEGF) and the change of microvessel density (MVD) in the remnant kidney of rats that undergone 5/6 subtotal nephrectomy (STNx). METHODS: The male Sprague-Dawley (SD) rats were performed 5/6 nephrectomy to produce chronic renal failure, and randomly divided into a model group (STNx group), a STNx combined with benazepril group (Benazepril group), and a sham group that served as normal controls. Pathological changes of the remnant kidney were evaluated at the 8th week after gastric gavage. Immunohistochemistry Methods were used to examine the expression of VEGF and MVD in the remnant kidney, and the correlation was determined between VEGF, MVD and glomerulosclerosis index (GSI), tubulointerstitial score (TIS), BUN, and creatinine (Cr). RESULTS: UP, BUN, Cr, GSI, and TIS significantly decreased in the benazepirl group (P<0.05); and the expression of VEGF and MVD significant increased (P<0.05). The expression of VEGF was positively related to MVD (P<0.05), and there was negative correlation between VEGF, MVD and GSI, TIS, BUN, Cr (P<0.05). CONCLUSION: The decrease of the expression of VEGF and MVD in the remnant kidney may be involved in the progressive remnant kidney fibrosis and renal function. Benazepril can significantly relieve the remnant kidney fibrosis and protect the renal function by increasing the expression of VEGF and MVD in the remnant kidney.

[Investigation and controlling measure of main diseases and pests on Artemisia annua].

According to the investigations in Guangxi area, there are 3 kind diseases and 11 kind insect pests on Artemisia annua L. In which main diseases and peste are the stem rot, cataplexy, Myzus persicase, Agrotis ypsilon and Diarthronomyia chrysanthemi. This article reports the main symptom, the cause of disease, the shape characteristic, the harm situation emphatically as well as the preventing and controlling measure.

[Expression of renal nuclear factor-kappaB, transforming growth factor-beta and fibronectin of rats exposed to lead].

OBJECTIVE: To investigate the role of lead in the expression of the renal fibrosis related nuclear factor kappaB (NF-kappaB), transforming growth factor (TGF-beta) and fibronectin (FN) in rat kidney and the possible molecule mechanism of lead induced renal fibrosis. METHODS: Thirty-two Sprague-Dawley rats were randomized into 4 groups. Group A was fed with distilled water as control group. Group B, C and D were fed with the water including 0.5% lead acetate continuously for 1, 2 or 3 months respectively. At the end of treatment, the expressions of renal NF-kappaB, TGF-beta and FN were detected by immunohistochemistry and RT-PCR. RESULTS: The immunohistochemistry analysis showed that expressions of NF-kappaB in group B, C and D (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839 respectively) were continuously increased as compared with that in group A (0.1464 +/- 0.0624). The RT-PCR analysis showed that expressions of NF-kappaB in group B, C and D (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538 respectively) were also increased as compared with that in group A (0.3608 +/- 0.0550). However, there was no change for TGF-beta in 4 groups except that it was increased markedly in group D (0.5225 +/- 0.0416) as compared with that in group A (0.4645 +/- 0.0461) by RT-PCR. The expressions of FN in group C and D (0.4243 +/- 0.0595 and 0.4917 +/- 0.0891 by immunohistochemistry; 0.8650 +/- 0.0880 and 0.8714 +/- 0.0980 by RT-PCR) were increased as compared with those in group A (0.3530 +/- 0.0490 by immunohistochemistry and 0.7432 +/- 0.0639 by RT-PCR). CONCLUSION: The lead can increase the expression of renal NF-kappaB, TGF-beta and FN in rats, which may be related to the lead induced renal fibrosis in rats.

[Multiple analysis of lead concentration in the air and renal function of lead exposure workers].

OBJECTIVE: To determine the lead concentration in the air (pbA) at the workplace and the renal function of lead exposure workers. METHODS: The lead concentration in the air of 11 printing plants, 4 smelteries and 2 lead mines were measured. Screening urinalysis was performed in 1190 long term lead exposed workers with urine sugar, protein and sigements. It one of the three was abnormal, the workers were given examination of renal function. The relationship between pbA and renal function were confirmed by mutiple linear. RESULTS: The concentrations of pbA in the printing plants, smelteries and lead mines were 0.07 mg/m3, 0.26 mg/m3 and 0.66 mg/m3 respectively. Altogether 157 cases had one and more abnormal renal function. The correlation of concentration PbA in the workplace and the renal function of lead exposure workers was shown (R = 0.894, P < 0.001, R2 = 0.799). The correlation coefficient of skewness of showed that PbA and Bpb. Upb. Bun Scr Usug. Ubeta2MG were positively correlated (P < 0.01 approximately 0.001); Ccr was negatively correlated (P =0.05). Upro, UNAG and Ualb were nonsignificant. CONCLUSION: The lead concentration in the air at the workplace is related to the renal functions of lead exposure workers. It is important to decrease the lead environment and to prevent renal damage.

[Adsorbent effect of activated carbon on small molecular uremic toxin and its influence factors].

OBJECTIVE: To analyze the adsorbent effect of activated carbon on uremic toxin and its influence factors. METHODS: Uremic toxins (urea, creatinine and uric acid) were dissolved in the distilled water to obtain uremic toxic solution. Activated carbon was added to the solution, and the concentrations of uremic toxins were measured at different time spots. To determine the influence factors, some possible related materials, such as bile, amino acid, Ringer's, solution of glucose, HCl or NaOH respectively were added simultaneously. RESULTS: The concentrations of toxins in uremic toxic solution decreased 5 min after adding the activated carbon. The concentration of urea was the lowest at 30 min, but it increased after 50 min; while the concentrations of creatinine and uric acid reached the lowest level from 10 to 30 min after adding the activated carbon, and maintained at the same level after that. The bile, amino acid, electrolyte, glucose and pH value did not influence the adsorption of uric acid significantly, but they influenced the adsorption of urea and creatinine. Bile and amino acid influenced the concentration of urea remarkably, following glucose, NaOH and HCl. The effect of pH 2.0 solution on the creatinine concentration was the most significant, following glucose. CONCLUSION: Activated carbon has adsorptive effect on uremic toxins, but its adsorptive effect decreases as time goes on. Bile, glucose, amino acid, NaOH and HCl can affect the adsorptive effect of activated carbon on uremic toxins to some extent.