Beneficial Effects of N-Acetylcysteine and Ebselen on Renal Ischemia/Reperfusion Injury

Abstract

Introduction: It has been demonstrated that peroxynitrite accompanies acute renal ischemia and contributes to the pathophysiology of renal damage. Therefore, we aimed to investigate the roles of N-acetylcysteine (NAC), a well-known powerful antioxidant, and ebselen (E), a scavenger of peroxynitrite, on renal injury induced by renal ischemia/reperfusion injury (IRI) of rat kidney. Materials and methods: Forty male Sprague–Dawley rats were divided into five groups: sham, renal IRI, renal IRI+NAC, renal IRI+E, and renal IRI+NAC+E. IR injury was induced by 60 min of bilateral renal ischemia followed by 6 h of reperfusion. After reperfusion, kidneys and blood samples were obtained for histopathological and biochemical evaluations. Results: Renal IR resulted in increased malondialdehyde and nitrite/nitrate levels suggesting increased lipid peroxidation and peroxynitrite production and decreased superoxide dismutase and glutathione peroxidase activities. Both NAC and E alone significantly decreased malondialdehyde and nitrite/nitrate levels and increased superoxide dismutase and glutathione peroxidase activities. Additionally in the renal IRI+NAC+E group, all biochemical results were quite close to those of sham group. Histopathologically, the kidney injury in rats treated with combination of NAC and E was found significantly less than the other groups. Conclusions: Both NAC and E are able to ameliorate IRI of the kidney by decreasing oxidative and nitrosative stresses and increasing free radical scavenger properties. Additionally, combination of NAC and E prevents kidney damage more than when each drug is used alone, suggesting that scavenging peroxynitrite nearby antioxidant activity is important in preventing renal IRI.     

Medical ozone therapy reduces shock wave therapy-induced renal injury

Objectives: Extracorporeal shock wave (ESW) lithotripsy is the preferred treatment modality for uncomplicated kidney stones. More recently free oxygen radical production following ESW application has been considered to be crucial in shock wave-induced renal damage. It has been shown that ozone therapy (OT) has ameliorative and preventive effects against various pathological conditions due to increased nitro-oxidative stress. In current study, we aimed to evaluate the efficacy of OT against ESW-induced renal injury. Methods: Twenty-four male Sprague–Dawley rats were divided into three groups: sham-operated, ESW, and ESW?+?OT groups. All groups except sham-operated group were subjected to ESW procedure. ESW?+?OT group received 1?mg/kg/day of oxygen/ozone mixture intraperitoneally at 2?h before ESW, and OT was continued once a day for consecutive three days. The animals were killed at the 4th day, and kidney tissue and blood samples were harvested for biochemical and histopathologic analysis. Results: Serum ALT and AST levels, serum neopterin, tissue nitrite/nitrate levels, and tissue oxidative stress parameters were increased in the ESW group and almost came close to control values in the treatment group (p?p?p?p?Conclusion: OT ameliorates nitro-oxidative stress and reduces the severity of pathological changes in the experimental ESW-induced renal injury of rat model.     

Carvedilol protects tubular epithelial cells from ischemia–reperfusion injury by inhibiting oxidative stress

Objectives: Renal ischemia–reperfusion injury (IRI), leading to acute kidney injury, is a frequent complication with renal transplantation and it is associated with graft function. Its pathogenesis involves ischemia, vascular congestion and reactive oxygen metabolites. Carvedilol is an antihypertensive drug with potent anti‐oxidant properties. In this study we investigated the protective effects of carvedilol in a rat renal IRI model. Methods: Twenty‐four rats were randomized into sham, untreated control and carvedilol (2 mg/kg 30 min before surgery and 12 hr after reperfusion) treatment groups and were subjected to 60 min of left renal ischemia followed by reperfusion at 24, 48, 96 and 168 hr. Results: Treatment with carvedilol significantly decreased plasma creatinine levels after IRI (up to 168 hr) compared to controls (P < 0.001), suggesting an improvement in renal function. Histopathological analysis revealed decreased IRI‐induced damage in kidneys from carvedilol‐treated rats. A significant increase in the expression levels of Cu/Zn superoxide dismutase and reduction of 8‐hydroxydeoxyguanosine and apoptosis levels (P < 0.005) suggested a protective effect after treatment with carvedilol. Conclusions: Our findings suggest that carvedilol ameliorates IRI resulting in improved renal function.     

Sinapic acid reduces ischemia/reperfusion injury due to testicular torsion/detorsion in rats

This study aimed to investigate the protective effect of sinapic acid (SA) on biochemical and histopathological changes in an experimental testicular torsion-detorsion rat model. Twenty-four rats were randomised into four groups: sham group, ischemia/reperfusion (IR) group subjected to testicular torsion for 2 hr and then detorsion for 4 hr, and two groups treated with SA1 and SA2 (10 mg/kg and 20 mg/kg, by single intraperitoneal injection, 30 min before reperfusion). Serum testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured by an autoanalyzer, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) oxidative stress parameters by spectrophotometric methods, and tumour necrosis factor (TNF-α), interleukin-1 beta (IL-1β), and interleukin 6 (IL-6) parameters by the Elisa method. In addition, immunohistochemical and histopathological examinations were performed on testicular tissues. There was no significant difference between the groups in terms of serum testosterone, FSH and LH levels (p > .05). SA significantly reduced increased testicular damage, oxidative stress, inflammation, cell death and also restored decreased antioxidant enzyme activities (p < .05). Pre-treatment of rats with SA reduced testicular dysfunction and morphological changes IRI. SA's antioxidant, anti-inflammatory, and antiapoptotic properties were found to be protective against testicular IR.     

Protective effect of theophylline on renal functions in experimental pneumoperitoneum model

Abstract

Our objective in this experimental study is to research the effect of the intra-abdominal pressure which rises following pneumoperitoneum and whether Theophylline has a possible protective activity on this situation. In our study, 24 Wistar Albino rats were used. Rats were divided into two groups. The first group was set for only pneumoperitoneum model. The second group was given 15?mg/kg of Theophylline intraperitoneally before setting pneumoperitoneum model. Then urea, creatinine, cystatin-C, tissue and serum total antioxidant capacity, total oxidant capacity and oxidative stress index in two groups were measured and compared with each other. Apoptosis and histopathological conditions in the renal tissues were examined. The differences between the groups were analyzed with the Mann–Whitney U test. Results were considered significant at p?<?0.05. No statistically significant difference was determined between tissue and serum averages in two groups in terms of TAS, TOS and OSI values (p?>?0.05). The mean value of urea were similar in pneumoperitoneum and pneumoperitoneum?+?theophylline groups (p?=?0.12). The mean cystatin-C value was 2.2?±?0.3?µg/mL in pneumoperitoneum, 1.74?±?0.33?µg/mL in pneumoperitoneum?+?theophylline (p?=?0.002). According to our study, lower cystatin-C levels in the group, where Theophylline was given, are suggestive of lower renal injury in this group. However, this opinion is interrogated as there is no difference in terms of tissue and serum TAS, TOS, OSI and urea values between the groups.     

Effects of dexpanthenol and N-acetylcysteine pretreatment in rats before renal ischemia/reperfusion injury

Background: We investigated the anti-inflammatory and protective effects of concomitant use of dexpanthenol (DXP) and N-acetylcysteine (NAC) induced ischemia/reperfusion (I/R) injury of kidney. Methods: Forty rats were randomly divided into 5 groups. In all groups except for Group 1(Sham), renal arteries bilaterally occluded with vascular clamp for IR injury. Group 1(Sham), received a single dose of 10?mL/kg isotonic saline daily by intraperitoneal (IP) injection for three days. Group 2(IR), received a single dose of 10?mL/kg isotonic saline daily by IP injection for three days. Group 3(IR?+?NAC), received 300?mg/kg NAC daily by IP injection for three days. Group 4(IR?+?DXP), received 500?mg/kg DXP daily by IP injection for three days. Group 5(IR?+?NAC?+?DXP), received 500?mg/kg DXP and 300?mg/kg NAC daily by IP injection for three days. Serum urea (BUN), creatinine (Cr) and neutrophil gelatinase-associated lipocalin (NGAL, lipocalin 2, siderocalin) levels were measured as kidney function tests. TNF-α levels were measured as inflammatory marker. Tissue sections were evaluated histopathologically under light microscopy. Results: IR?+?NAC?+?DXP group received both NAC and DXP before induction of renal I/R and as the biochemical and histopathological data revealed the results of the IR?+?NAC?+?DXP group and sham group were similar. Biochemically and histopathologically, combined use of NAC and DXP has better results when each of them used alone. Conclusion: We concluded that concomitant use of DXP and NAC plays a major role against I/R injury and may be useful in acute treatment of I/R induced renal failure.     

L-Carnitine inhibits eryptosis induced by uremic serum and the related mechanisms

Abstract

Objective: To investigate whether L-carnitine (LC) inhibits eryptosis induced by uremic serum and the related mechanism. Methods: One percent erythrocyte suspension was cultured by three kinds of mediums in vitro, which was included in the control group (Group C, phosphate buffered saline [PBS]), the uremic serum group (Group U, 30% uremic serum?+?70% PBS) and the LC group (Group L, 30% uremic serum?+?70% PBS?+?200?umol/L LC), respectively. Erythrocytes were collected at 24 and 48?h, respectively. Phosphatidylserine (PS) was estimated from Annexin-V-binding and reactive oxygen species (ROS) by flow cytometry, glutathione (GSH) was estimated from Enzyme linked immunosorbent assays (ELISA) by Microplate reader. Results: Eryptosis in Group C increased as the incubating time extended (3.43?±?0.37 at 24?h, 4.21?±?0.44 at 48?h). Eryptosis increased in Group U compared with Group C (6.5 1?±?0.71 at 24?h, p?<?0.01; 8.55?±?0.76 at 48?h, p?<?0.01), while decreased in Group L compared with Group U (5.80?±?0.69 at 24?h, p?<?0.05; 7.87?±?0.76 at 48?h, p?<?0.05). Meanwhile, ROS of erythrocytes increased in Group U compared with Group C (33.12?±?1.61 versus 14.83?±?2.22 at 24?h, p?<?0.01; 42.06?±?1.81 versus 20.94?±?1.78 at 48?h, p?<?0.01), and GSH decreased in Group U compared with Group C (25.66?±?0.32 versus 31.27?±?0.38 at 24?h, p?<?0.01; 8.53?±?0.59 versus 17.29?±?0.54 at 48?h, p?<?0.01). ROS of erythrocytes decreased in Group L compared with Group C (26.29?±?1.69 at 24?h, p?<?0.01; 36.21?±?2.00 at 48?h, p?<?0.01). GSH increased in Group L compared with Group U (27.54?±?0.60 at 24?h, p?<?0.01; 15.18?±?0.42 at 48?h, p?<?0.01). Conclusions: LC inhibits eryptosis induced by uremic serum, which possibly relates to oxidative stress in part.     

Xuezhikang ameliorates contrast media-induced nephropathy in rats via suppression of oxidative stress,inflammatory responses and apoptosis

Background: The aim of this study was to assess the preventive effect of xuezhikang (XZK) to replace atorvastatin on the contrast media-induced acute kidney injury (CI-AKI).

Methods: The male Sprague–Dawley rats were divided into five groups: group 1 (sham), injected with normal saline; group 2 (XZK), treated with XZK; group 3 contrast media (CM), injected with CM; group 4 (CM?+?ATO), injected with CM?+?pretreatment with atorvastatin; group 5 (CM?+?XZK), injected with CM?+?pretreatment with XZK. Twenty-four hours after injection with normal saline or CM, the blood sample and the kidneys were collected for the measurement of biochemical parameters, oxidative stress markers, nitric oxide production, inflammatory parameters, as well as renal histopathology and apoptosis detection.

Results: Our results indicated that XZK restored the renal function by reducing serum blood urea nitrogen (BUN) and serum creatinine (Scr), depressing renal malondialdehyde (MDA), increasing renal NO production, decreasing TNF-ɑ and IL-6 expression, attenuating renal pathological changes and inhibiting the apoptosis of renal tubular cells.

Conclusion: XZK’s therapeutic effect is similar, or even better than atorvastatin at the same effectual dose in some parts.     

纤维蛋白肽Bβ15～42对大鼠缺血再灌注损伤肾脏局部炎性反应的影响

目的 观察纤维蛋白肽Bβ15～42(the fibrin-derived peptide Bβ15-42,FgBβ15～42肽)对大鼠肾脏缺血再灌注损伤(IRI)后肾脏局部炎性反应的影响并探讨其机制.方法 将SD大鼠随机分成假手术组(Sham组)、IRI组、阴性治疗组和FgBβ15 ～ 42肽治疗组.Sham组:分离肾动脉后关闭腹腔;IRI组:采用双侧肾动脉夹闭的方法制作肾脏IRI模型;阴性治疗组:于肾脏再灌注后立即尾静脉注射随机肽段3.6 mg/kg; FgBβ15～42肽治疗组:于肾脏再灌注后立即尾静脉注射FgBβ15～ 42肽3.6 mg/kg.后3组按照再灌注24h、48 h分为两个亚组,Sham组与各亚组均为8只大鼠.常规生化法检测肾功能;HE、PAS染色观察肾脏组织学改变;免疫组化、实时荧光定量PCR法及Western印迹检测肾组织白细胞介素1β(IL-1β)、细胞间黏附分子1(ICAM-1)的mRNA及蛋白表达.结果 与Sham组相比,IRI组的Scr和BUN水平均显著增加(均P ＜0.05),肾小管及间质病理损伤显著,以再灌注48 h更为明显;与IRI组相比,FgBβ15～ 42肽治疗组Scr和BUN显著下降(均P＜0.05),小管间质损伤程度明显减轻(P＜0.05).与Sham组相比,IRI组IL-1β和ICA M-1的mRNA和蛋白水平于再灌注24h显著上升,48 h稍微下降,但仍维持在较高水平;FgBβ15～ 42肽治疗组大鼠肾组织IL-1β和ICAM-1的表达于再灌注24h、48 h显著低于同时间点的IRI组(均P＜0.05),但仍明显高于Sham组.上述各指标在阴性治疗组和IRI组之间的表达差异无统计学意义.结论 FgBβ15～42肽对肾脏IRI具有保护作用,其作用机制可能与其减少炎性因子IL-1β、黏附分子ICAM-1的表达有关.     

Iron restriction prevents diabetic nephropathy in Otsuka Long-Evans Tokushima fatty rat

Abstract

High body iron levels are found in type 2 diabetes mellitus (DM). Iron excess leads to tissue injury through free radical formation. We investigated the effect of iron restriction on renal damage in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2?DM. OLETF rats (n?=?18) were divided into three groups at 10 weeks of age: high fat diet containing 8% NaCl (HFS, n?=?6), HFS diet with iron restricted (HFS?+?IR, n?=?6), and HFS with hydralazine (HFS?+?Hyd, n?=?6). Long-Evans Tokushima (LETO) rats served as control. Iron restriction decreased hemoglobin levels, systolic blood pressure, and urinary excretion of protein and 8-hydroxy-2'-deoxyguanosine in the OLETF rats fed with HFS diet. Compared to the HFS group, the expression of desmin, renal glomerular injury marker and iron deposition in the renal tubules were attenuated in the HFS?+?IR group but not in the HFS?+?Hyd group at 26 weeks of age. Moreover, renal hypoxia (evaluated as pimonidazole adducts) was improved in the HFS?+?IR group compared to the HFS group in spite of anemia. Iron restriction prevented the production of reactive oxygen species and the development of early stage nephropathy in OLETF rats. Iron restriction may be beneficial in prevention of nephropathy in type 2?DM.     

Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia

Abstract

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondria-targeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. Method: Forty SD rats were randomly divided into normal diet group (NN, n?=?8) and high cholesterol supplemented dietary group (HN, n?=?32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10?mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3?mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p?<?0.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p?<?0.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p?<?0.01). The renal injuries induced by contrast media (CM) were alleviated. Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.     

Micro RNA-320 as a novel potential biomarker in renal ischemia reperfusion

Aim: MicroRNAs (miR) are important diagnostic and treatment targets due to their different tissue expressions and their central position in the regulation of gene expressions. miR studies might pioneer emerging of new diagnostic tools and treatment goals in kidney diseases. Captopril (CAP) and telmisartan (TEL) were shown to be effective in ischemia reperfusion (IR) injury. There is not any study about the effect of TEL and CAP over miR-21-320-146a. Our aim was to study the effects of CAP and TEL over miR on renal IR model.

Methods: We used 12–16 weeks-old Wistar-Albino rats that weigh 300–350?g. Rats (n, 6) were randomized into four groups (Control, IR, IR?+?CAP, IR?+?TEL). Urea, creatinine, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), super oxide dismutase (SOD), and miRs were analyzed.

Results: Urea, creatinine, TOS, OSI levels of IR?+?CAP, and IR?+?TEL groups were lower comparing to IR group. TAS and SOD levels were higher in IR group than IR?+?TEL group. miR-21-320-146a showed increase in renal IR injury. miR-320, 146a showed significant decrease in IR?+?CAP and IR?+?TEL groups comparing to IR group. We showed histopathological recovery and decreased apoptosis in IR?+?CAP and IR?+?T groups than IR group.

Conclusion: We, for the first time in the literature, showed that miR-320 is increased in IR injury. miR-320 might be a novel diagnosis and treatment target in renal ischemic reperfusion injury. Also, for the first time, we showed that CAP and TEL cause functional and histopathological recovery and lower miR-146a and miR-320.     

The effect of hypericum perforatum on kidney ischemia/reperfusion damage

It has been revealed in recent studies that Hypericum Perforatum (HP) is influential on cancer, inflammatory diseases, bacterial and viral diseases, and has neuroprotective and antioxidant properties. In this study, we investigated the effect of HP, which is known to have antioxidant and anti-inflammatory effects, on kidney I/R damage. Male Sprague–Dawley rats were divided into three groups, and each of the groups had eight rats: The Control Group; the Ischemia/Reperfusion (I/R) Group; and the IR?+?HP Group which was treated with 50?mg/kg of HP. The right kidneys of the rats were removed, and the left kidney developed ischemia during the 45th min, and reperfusion occurred in the following 3rd h. The histopathological findings and also the level of Malondialdehyde (MDA), Glutathione (GSH) and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) enzyme activations in the renal tissues were measured. Blood Urea Nitrogen (BUN), Creatinin (Cre) from serum samples were determined. The levels of BUN, Cre, and kidney tissue MDA increased at a significant level, and the SOD, CAT, and GSH-PX enzyme activity decreased at a significant level in the I/R group, compared with the Control Group (p?p?相似文献   

Protective Effect of Alpha 1-Antitrypsin on Renal Ischemia-Reperfusion Injury

Backgroundα₁-Antitrypsin (AAT) is an important protein in the anti-inflammatory response that functions to regulate the activity of serine proteinases. We aimed to evaluate the protective effect of AAT on ischemia-reperfusion injury (IRI) in a mouse model.MethodsWe investigated the effects of AAT in a C57BL/6 mouse model of IRI by dividing them into 4 groups: normal control, sham operated, ischemia-reperfusion (IR), and IR after AAT pretreatment (IR-AAT). In the IR-AAT group, mice were pretreated with AAT (80 mg/kg/d) for 3 days before renal ischemia was induced by clamping the bilateral renal vascular pedicles for 30 minutes. At 24 hours after IRI, biochemistry, histology, inflammatory cytokines, and apoptosis were assayed.ResultsBlood urea nitrogen and serum creatinine levels were significantly lower in the IR-AAT group than in the IR group. Neutrophil gelatinase-associated lipocalin and kidney injury molecule 1 protein levels were significantly lower in the IR-AAT group than in the IR group. In addition, there were fewer tubular injuries and less interstitial fibrosis in the IR-AAT group than in the IR group, and the expression levels of transforming growth factor β, interleukin 1β, and interleukin 6 were significantly lower in the IR-AAT group than in the IR group. When compared with the IR group, there were fewer terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay–positive cells, lower caspase 3 activity and B-cell lymphoma 2-associated X protein (Bax), and higher B-cell lymphoma 2 (Bcl–2) in the IR-AAT group.Conclusionsα₁-Antitrypsin preserved renal function, attenuated tubular injuries and interstitial fibrosis, and inhibited inflammation and apoptosis after renal IRI. Our results suggest that AAT has protective effects against renal IRI by inhibiting inflammatory and apoptosis pathways.     

Efficacy of poly(adenosine diphosphate-ribose) polymerase inhibition in extracorporeal shock wave-induced renal injury

Objectives: Extracorporeal shock wave lithotripsy (ESW) induces renal damage by excessive production of free oxygen radicals. Free Oxygen radicals cause cellular injury by inducing nicks in DNA. The enzyme poly(adenosine diphosphate-ribose) polymerase (PARP) involved in the process of repair of DNA in damaged cells. However, its activation in damaged cells can lead to adenosine triphosphate depletion and death. Thus, we designed a study to evaluate the efficacy of 3-aminobenzamide (3-AB), a PARP inhibitor, against extracorporeal shock wave induced renal injury. Methods: Twenty-four Sprague-Dawley rats were divided into three groups: control, ESW, ESW?+?3-AB groups. All groups except control group were subjected to ESW procedure. ESW?+?3-AB group received 20?mg/kg/day 3-aminobenzamide intraperitoneally at 2?h before ESW and continued once a day for consecutive 3 days. The surviving animals were sacrificed at the 4th day and their kidneys were harvested for biochemical and histopathologic analysis. Blood samples from animals were also obtained. Results: Serum ALT and AST levels, serum neopterin and tissue oxidative stress parameters were increased in the ESW group and almost came to control values in the treatment group (p?p?Conclusion: Our data showed that PARP inhibition protected renal tissue against ESW induced renal injury. These findings suggest that it would be possible to improve the outcome of ESW induced renal injury by using PARP inhibitors as a preventive therapy.     

外源性硫化氢抑制TLR2和TLR4表达并减轻大鼠肾脏缺血再灌注损伤

目的观察外源性硫化氢(H₂S)供体硫氢化钠(NaHS)能否抑制Toll样受体2(TLR2)和Toll样受体4(TLR4)表达、减轻大鼠肾脏缺血再灌注损伤(IRI)。 方法24只6~8周龄雄性SD大鼠随机分为3组：假手术(Sham)组、肾脏缺血再灌注(I/R)组、NaHS+I/R组。采用右肾切除联合左肾动脉夹闭45 min后再灌注24 h的方法诱导肾IRI。夹闭左肾动脉前，NaHS+I/R组给予NaHS(300 nmol/min)连续输注10 min，Sham组和I/R组则给予等体积生理盐水。分别留取各组腹主动脉血及肾组织标本。Western印迹法检测肾组织TLR2、TLR4蛋白的表达；免疫组织化学法检测肾组织白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)的表达；比色法检测血尿素氮(BUN)、血肌酐(Scr)。HE染色观察肾脏组织学改变；TUNEL法检测肾组织细胞凋亡。 结果与Sham组比较，I/R组的TLR2、TLR4、IL-6、TNF-α表达均增加(P<0.05)，BUN、Scr亦明显升高(P<0.05)，肾小管上皮损伤评分较高(P<0.05)，肾组织凋亡细胞增加(P<0.05)。与I/R组比较，NaHS+I/R组的TLR2、TLR4、IL-6、TNF-α表达均减少(P<0.05)，BUN、Scr亦明显下降(P<0.05)，肾小管上皮损伤评分较低(P<0.05)，肾组织凋亡细胞减少(P<0.05)。 结论外源性H₂S可以抑制TLR2、TLR4途径，减少炎症因子释放及细胞凋亡，减轻大鼠肾脏IRI。     

Imbalance in the estrogen/androgen ratio may affect prostate fibrosis through the TGF-β/Smad signaling pathway

Objective

The present study aimed to investigate the effects of an imbalance in the estrogen/androgen ratio on prostate fibrosis.

Methods

Different concentrations of dihydrotestosterone (DHT) or estradiol (E₂) dissolved in corn oil were injected subcutaneously into the nape of the castrated Sprague–Dawley (SD) rats over 28 consecutive days. Masson’s trichrome staining and immunohistochemical staining were performed to detect the content of collagen fibers and the expression of collagen I, fibronectin, and elastin in the rat prostate of each group, respectively. DHT?+?E₂ at different concentrations was administered to human normal prostate stromal immortalized cells (WPMY-1 cells) for 1 week. The expression of collagen I, fibronectin, elastin, transforming growth factor-β₁ (TGF-β₁), Smad3, and Smad7 was detected by Western blotting (WB). Then, WPMY-1 cells treated with 10 nM DHT?+?5 pM E₂ were incubated with the TGF-β/Smad pathway inhibitor SD208 for 1 week, after which collagen I, fibronectin, and elastin expression was detected by WB.

Results

Compared with the uncastrated control and corn oil injection groups, the collagen fiber content and collagen I and fibronectin expression were increased and elastin expression was decreased in the castrated rat prostate with corn oil injection group (p?<?0.01). Compared to castrated corn oil injection group, collagen fiber content, collagen I, and fibronectin expression were significantly decreased, and elastin expression was significantly increased in the castrated rat prostate 0.15 mg/kg DHT treatment group (p?<?0.01). Following treatment with 0.15 mg/kg DHT, the content of collagen fibers, and the expression of collagen I and fibronectin were increased, and the expression of elastin was decreased in the rat prostate with increasing concentrations of E₂ treatment group compared to the 0.15 mg/kg DHT group (p?<?0.05, p?<?0.01). Following treatment with 0.05 mg/kg E₂, the collagen fiber content and the expression of collagen I and fibronectin were decreased, and the expression of elastin was increased in the rat prostate with increasing DHT concentration treatment group compared to the 0.05 mg/kg E₂ group (p?<?0.05, p?<?0.01). Compared with the Control group, the expression of collagen I, fibronectin, TGF-β₁ and Smad3 was decreased, and the expression of elastin and Smad7 was increased in WPMY-1 cells after treatment with 10 nM DHT (p?<?0.01). Following treatment with 10 nM DHT, the expression of collagen I, fibronectin, TGF-β₁, and Smad3 was increased, and the expression of elastin and Smad7 was decreased in WPMY-1 cells with increasing E₂ concentration treatment compared to the 10 nM DHT group (p?<?0.05, p?<?0.01). Following treatment with 5 pM E₂, the expression of collagen I, fibronectin, TGF-β₁, and Smad3 was decreased, and elastin and Smad7 expression was increased with increasing DHT concentration compared to the 5 pM E₂ group (p?<?0.05, p?<?0.01). Compared to the 10 nM DHT?+?5 pM E₂ group, the expressions of collagen I and fibronectin were decreased; the expression of elastin was increased in WPMY-1 cells after the supplement of TGF-β/Smad pathway inhibitor SD208 group (p?<?0.05, p?<?0.01).

Conclusions

An imbalance in the estrogen/androgen ratio may affect prostate fibrosis. E₂ may activate the degree of prostate fibrosis. In contrast to the effect of E₂, DHT may inhibit the degree of prostate fibrosis, which might involve the TGF-β/Smad signaling pathway.

     

Short-term clinical and osteoimmunological effects of scaling and root planing complemented by simple or repeated laser phototherapy in chronic periodontitis

The aim of this study was to evaluate the clinical, anti-inflammatory, and osteoimmunological benefits of the single (PT) and repeated laser phototherapy (rPT) as an adjunctive treatment of inflamed periodontal tissue. Twenty-seven patients with chronic periodontitis were randomly divided into three groups of nine patients each in order to undergo scaling and root planing (SRP), SRP followed by one session of adjunctive PT (Day 1; SRP?+?PT), or SRP followed by adjunctive repeated PT five times in 2 weeks (Days 1, 2, 4, 7, and 11; SRP?+?rPT). For phototherapy session, a diode laser (λ?=?670 nm, 200 mW, 60 s/tooth) was applied into the sulcus. Clinical parameters, including full-mouth plaque score, full-mouth bleeding score, probing pocket depth, and clinical attachment level were recorded. Samples of gingival crevicular fluid (GCF) were taken at baseline, 4, and 8 weeks after treatment. Interleukin 1beta (IL-1β), tumor necrosis factor alpha (TNF-α), receptor activator of nuclear factor κΒ ligand (RANKL), and osteoprotegerin (OPG) levels in the collected GCF were measured. PT used in a single or repeated doses, does not produce a significant reduction in the clinical parameters essayed (p?>?0.05). Levels of IL-1β in GCF were significantly reduced in SRP?+?PT and SRP?+?rPT groups compared with the SRP group (p?<?0.05). However, the SRP?+?rPT group showed a significant reduction of pro-inflammatory cytokine TNF-α and RANKL/OPG ratio at 4 weeks post-treatment compared with the SRP?+?PT and SRP groups (p?<?0.05). SRP?+?PT group also showed a significant reduction in TNF-α and RANKL/OPG ratio at 8 weeks post-treatment compared with the SRP group (p?<?0.05). PT exerts a biostimulative effect on the periodontal tissue. Multiple sessions of PT showed a faster and greater tendency to reduce proinflammatory mediators and RANKL/OPG ratio.