Comparative Study of Cardiovascular Effects of Selected Pulmonary Vasodilators in Canine Models of Mitral Valve Disease.

Previous reports have shown that various oral pulmonary vasodilators are effective against canine pulmonary hypertension (PH). However, no studies have compared their hemodynamic effects. We aimed to compare the hemodynamic effects of 15 µg/kg beraprost sodium, 1.0 mg/kg sildenafil, and their combination, in dogs with experimentally induced mitral regurgitation. This experimental crossover study evaluated the hemodynamic and functional effects of oral pulmonary vasodilators by application of right-sided heart catheterization and echocardiography. Beraprost significantly decreased pulmonary and systemic vascular resistance. Additionally, beraprost increased right-ventricular stroke volume and left-ventricular cardiac output without worsening left-heart size and left-atrial pressure. The pulmonary vasodilatory effects of sildenafil were stronger, and its systemic vasodilatory effects were weaker than those of beraprost. However, sildenafil significantly increased the left-ventricular volume, left-atrial pressure indicator, and right-ventricular cardiac output. Combination therapy resulted in the strongest pulmonary and systemic vasodilating effects without worsening the left-heart size and left-atrial pressure indicators. Both beraprost and sildenafil were effective against canine PH; however, sildenafil was associated with the risk of worsening left-heart loading. Combination therapy with beraprost and sildenafil synergistically dilated pulmonary and systemic vessels, indicating a more potent treatment option for severe PH cases.

Pulmonary thrombotic pulmonary hypertension managed using antithrombotic and pulmonary vasodilator treatment.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

Clinical efficacy of beraprost sodium in treating chronic kidney disease: A six-month prospective study.

Objective: To investigate the clinical efficacy of beraprost sodium (BPS) in the treatment of chronic kidney disease (CKD). Methods: In this single-centre, prospective, controlled, single-blind study, 252 patients diagnosed with CKD and treated at the Affiliated Hospital of Xuzhou Medical University were enrolled from September 2018 to June 2021. All participants were randomised into three groups: the control, BPS 40 µg, and BPS 20 µg groups. Both treatment groups were administered conventional therapy for 6 months. Renal function in the three groups was measured and compared 3 and 6 months post-treatment. Results: 1. Renal function in the BPS 20 µg and BPS 40 µg groups was better than that in the control group after 3 and 6 months of treatment. 2. After 3 months of treatment, the levels of serum creatinine (P = 0.043), cystatin C (P = 0.039), and 24 h urinary total protein (P = 0.041) in the BPS 40 µg group were significantly lower than those in the BPS 20 µg group, the eGFR (P = 0.046) level was higher than that in the BPS 20 µg group, and the index improvement rate was better than that in the BPS 20 µg group (P < 0.05). 3. After 6 months of treatment, the improvement in renal function in the BPS 20 µg group was close to that in the BPS 40 µg group (P > 0.05). Conclusion: BPS improved renal function, reduced urinary protein levels, and delayed CKD progression. The clinical efficacy of BPS in the 40 µg group was faster than that in the BPS 20 µg group. The long-term use of BPS is effective in patients with CKD.

Beraprost sodium attenuates the development of myocardial fibrosis after myocardial infarction by regulating GSK-3ß expression in rats.

OBJECTIVE: The aim of this study was to elucidate the mechanism of beraprost sodium (BPS) in the intervention of myocardial fibrosis after myocardial infarction (MI) through glycogen synthase kinase-3ß (GSK-3ß) and to provide new ideas for intervention in myocardial fibrosis. MATERIALS AND METHODS: MI model rats given BPS and cardiac fibroblasts (CFs) treated with BPS and TGF-ß. HE staining and Masson staining were used to detect the pathological changes of myocardial tissue. Fibrotic markers were detected by immunohistochemical staining. The expressions of GSK-3ß, cAMP response element binding protein (CREB), and p-CREB were analyzed by qPCR and western blot analysis. EDU staining was used to detect the proliferation of CFs. The promoter activity of GSK-3ß was detected by luciferase assay. Chromatin immunoprecipitation assay was used to detect the binding levels of GSK-3ß promoter and Y-box binding protein 1 (YBX1). The levels of intracellular cyclic adenosine monophosphate (cAMP) were analyzed by enzyme-linked immunosorbent assay (ELISA). RESULTS: After operation, BPS improved myocardial fibrosis and upregulated GSK-3ß protein expression in male SD rats. BPS can down-regulate α-smooth muscle actin (α-SMA) level and up-regulate GSK-3ß protein expression in CFs after TGF-ß stimulation. Furthermore, GSK-3ß knockdown can reverse the effect of BPS on TGF-ß-activated CFs, enhance α-SMA expression, and promote the proliferation of CFs. BPS could regulate GSK-3ß expression by promoting the binding of GSK-3ß promoter to YBX1. BPS induced upregulation of p-CREB and cAMP, resulting in reduced fibrosis, which was reversed by the knockdown of GSK-3ß or prostaglandin receptor (IPR) antagonists. CONCLUSION: BPS treatment increased the binding of YBX1 to the GSK-3ß promoter, and GSK-3ß protein expression was upregulated, which further caused the upregulation of p-CREB and cAMP, and finally inhibited myocardial fibrosis.

Beraprost Sodium Delays the Decline of Glomerular Filtration Rate in Patients with Diabetic Nephropathy: A Retrospective Study.

INTRODUCTION: To investigate the reno-protective effect of beraprost sodium (BPS) in patients with diabetic nephropathy (DN). METHODS: We retrospectively analyzed patients with DN hospitalized in China-Japan Friendship Hospital from January 2015 to December 2021 who received combination of conventional treatment and BPS (120 ug/day) therapy. We selected patients with DN matched in age and estimated glomerular filtration rate (eGFR) as controls, who received only conventional therapy. Baseline information and clinical variables at each follow-up visit were collected from all patients. The changes of clinical variables were compared between the two groups before and after treatment. RESULTS: A total of 50 patients with DN met the inclusion and exclusion criteria, with 25 patients in each group. The baseline characteristics of the two groups have no significant difference (p > 0.05). Serum albumin levels after treatment were improved in both groups, but the improvement was statistically significant only in BPS group (35.5-39.8 g/l, p < 0.001). The eGFR worsened significantly in both groups (p = 0.009 and p = 0.001). However, the decline of eGFR was less in BPS group than that in control group (- 9.8 vs. - 16.7 ml/min/1.73 m2, p = 0.037). In the subgroup analysis, 30 patients received 3-12 months treatment and 20 patients received more than 12 months treatment. During the 3-12 months treatment period, serum creatinine and eGFR in the control group were significantly worsened compared with those before treatment (p = 0.019 and p = 0.03), but in the BPS group they were relatively stable (p > 0.05). After more than 12 months treatment, although the serum creatinine and eGFR were significantly worsened in both groups (p < 0.05), the decline of eGFR was less in BPS group than that in control group (- 10.1 vs. - 25.9 ml/min/1.73 m2, p = 0.045). CONCLUSIONS: Combination of conventional treatment and BPS therapy delays the decline of eGFR in patients with DN in the long term.

Ultrasonography evaluation on the protective effect of combination therapy of beraprost sodium and aspirin on arteries occlusion and stiffness in patients with type 2 diabetes mellitus - a prospective, randomized study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are susceptible to developing symptomatic peripheral arterial disease (PAD). As a proven vasodilator and antiplatelet agent, the efficiency of Beraprost sodium (BPS) on the prevention of arteries occlusion and stiffness in T2DM patients with PAD has not yet been fully investigated. METHODS: From July 2010 to April 2012, 64 Patients enrolled were randomly assigned to the combined therapy group (n=32), which received combination therapy with BPS (60 µg/day) and aspirin (100 mg/day), or to the control group (n=32), which only received aspirin (100 mg/day). After randomization, the patients were followed up at years 0, 1, 2, 3, 4, and 5 with the evaluation of carotid intima-media thickness (CIMT), pulse wave velocity (PWV), inner artery diameter, stenosis rate, and medial arterial calcification (MAC) of lower limb arteries via high-resolution ultrasound measurement. Adverse events were also recorded in each visit. RESULTS: There was no significant change of the CIMT during the follow-up in both groups when compared to the baseline. Similar results were also observed in the PWV measurement. Significantly increases in the inner artery diameter of the dorsal pedal artery and posterior tibial artery were observed in patients with BPS and aspirin administration during the follow-up. Patients in the combined therapy group experienced marked improvement of MAC in the dorsal pedal artery and posterior tibial artery at the end of the follow-up. No significant difference in the adverse events was found between the combined therapy group and the aspirin group. CONCLUSION: The combined therapy of BPS and aspirin showed a protective effect on arteries occlusion and stiffness in T2DM patients with PAD, along with a significant improvement of inner artery diameter and MAC in lower limbs. TRIAL REGISTRATION: http://www.chictr.org.cn , ChiCTR-TRC-10000919. Prospectively registered on 2010/06/29.

Clinical efficacy and safety of electro-acupuncture combined with beraprost sodium and α-lipoic acid for diabetic peripheral neuropathy.

BACKGROUND: The pathogenic triggers of diabetic peripheral neuropathy (DPN) mainly include ischemia and hypoxic factors. The combined use of Chinese and Western medicine may be a new perspective for the treatment of DPN. Accordingly, this study explores the clinical efficacy and safety of electro-acupuncture (EA) combined with beraprost sodium (BPS) and α-lipoic acid (α-LA) in the treatment of patients with DPN. METHODS: A total of 184 patients with DPN meeting the inclusion criteria were enrolled and divided into electric-acupuncture group (n=54), medication group (n=62) and combination group (n=68), which were treated by EA, BPS+α-LA, and EA+BPS+α-LA, respectively. The three groups were compared with respect to the following factors: clinical efficacy; motor conduction velocities (MCVs) of nervus medianus, nervus peroneus communis and tibial nerve and sensory conduction velocities (SCVs) of nervus medianus, sural nerve and ulnar nerve before and after treatment; the Toronto Clinical Scoring System (TCSS), total symptom score (TSS) and Michigan Diabetes Neuropathy Score (MDNS) before and after treatment; changes of serum homocysteine and cysteine (Cys) levels, oxidative stress indicators and inflammatory factors; incidence of adverse reactions. RESULTS: The overall response rate of the combination group was higher than that of the electric acupuncture group or the medication group. After treatment, the SCV of nervus medianus, sural nerve and ulnar nerve and the MCV of nervus medianus, nervus peroneus communis and tibial nerve were the highest in the combination group among the three groups (P<0.05). After treatment, the scores of TCSS, TSS and MDNS in the combination group was notably lower than those in the medication group and the electric acupuncture group (P<0.05). The amelioration of inflammatory factors in the combination group were the best among the three groups (P<0.05). The incidence of adverse reactions was lower in the combination group compared with the electric acupuncture group and the medication group (P<0.05). CONCLUSION: EA combined with BPS and α-LA is effective in the treatment of DPN, which can effectively reduce the levels of serum inflammatory factors in patients, with a lower complication rate and higher safety.

The effects of beraprost sodium on renal function and cardiometabolic profile in patients with diabetes mellitus: a systematic review and meta-analysis of clinical trials.

PURPOSE: This systematic review and meta-analysis aimed to assess renal function and cardiometabolic biomarkers after treatment with beraprost sodium in patients with diabetes mellitus. METHODS: We systemically searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to August 2020. Statistical heterogeneities were computed using Cochrane's Q test and I2 test. A fixed- or random-effects model was used to calculate the weighted mean difference (WMD) and corresponding 95% confidence intervals (CI). RESULTS: From 341citations, seven trials were included into our meta-analysis. Our findings demonstrated that beraprost sodium intake significantly decreased blood urea nitrogen (BUN) (WMD = -5.62, 95% CI [-8.49, -2.74], P < 0.001) and cystatin C (WMD = -0.57, 95% CI [-0.68, -0.46], P < 0.001). Beraprost sodium intake had no significant effect on fasting blood sugar (FBS), hemoglobin A1c (HbA1c), cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, systolic blood pressure (SBP), diastolic blood pressure (DBP), and creatinine (Cr) in patients with diabetes receiving beraprost sodium in comparison with the controls. CONCLUSION: Our meta-analysis revealed that beraprost sodium administration significantly decreased BUN and cystatin C levels in patients with diabetes. However, no significant effect was observed on the cardiometabolic profile.

Prostacyclin analog beraprost sodium efficacy in primary glomerular disease or nephrosclerosis: Analysis of the Japanese subgroup in CASSIOPEIR study.

We conducted a multicenter, randomized, double-blind, placebo-controlled, phase IIb/III study (CASSIOPEIR) using a renal composite endpoint (i.e., doubling of SCr or end-stage renal disease) in seven Asian countries/region. CASSIOPEIR compared TRK-100STP (120 µg and 240 µg) with placebo in patients with non-diabetic CKD patients with primary glomerular disease or nephrosclerosis (n = 892). However, the superiority of TRK-100STP over placebo was not observed. A prior phase II study on which the Phase IIb/III study design was based included only Japanese patients. We therefore evaluated TRK-100STP efficacy and safety in a subgroup of Japanese patients using the CASSIOPEIR dataset. As the timing of treatment initiation is important in CKD, we conducted additional subgroup analyses based on the baseline serum creatinine (SCr) and eGFR. ITT analysis was performed in a Japanese subgroup (n = 339) in which the primary endpoint was the first occurrence of renal composite endpoint. Significant differences were observed for TRK-100STP 240 µg vs. placebo (P = 0.0493; HR 0.69 [95% CI: 0.47, 1.00]), but no significant difference was observed between TRK-100 120 µg and placebo (P = 0.3523; HR 0.85). More prominent improvement was observed with TRK-100STP 240 µg vs. placebo for baseline SCr < 3.0 mg/dL (P = 0.0031; HR 0.43); SCr < 3.5 mg/dL (P = 0.0237, HR 0.59); and eGFR ≥ 10 mL/min/1.73 m2 (P = 0.0339, HR0.67), respectively. No significant changes in urinary albumin/creatinine ratio and blood pressure were observed. TRK-100STP was generally well tolerated and most adverse drug reactions were mild or moderate in severity. In conclusion, in the Japanese subgroup of CASSIOPEIR, TRK-100STP 240 µg/day significantly improved the renal composite endpoint compared with placebo, with greater efficacy in subjects with SCr < 3.5 or eGFR ≥ 10 mL/min/1.73 m2 .

Inhibitory Effects of Beraprost Sodium in Murine Hepatic Sinusoidal Obstruction Syndrome.

BACKGROUND/AIM: In this study, the liver sinusoidal endothelial cells (LSECs)-protective effects of beraprost sodium (BPS) were investigated using mice with monocrotaline (MCT)-induced sinusoidal obstruction syndrome (SOS). MATERIALS AND METHODS: The mice were divided into BPS, placebo and control groups. They were killed 48 h after MCT administration, and blood samples and liver tissues were evaluated. Immunostaining was performed using anti-SE-1 and anti-CD42b antibodies, whereas plasminogen activator inhibitor (PAI-1) and endothelial nitric oxide synthase (eNOS) levels were evaluated using western blot or real-time RT-PCR. RESULTS: On pathological examination, SOS-related findings were observed in zone 3 in the placebo group; however, these were significantly suppressed in the BPS group. SE-1 staining showed a consistent number of LSECs in the BPS group compared with that in the placebo group, while CD42b staining showed a significant decrease in the number of extravasated platelet aggregation (EPA) in the BPS group. PAI-1 expression was significantly lower in the BPS group than in the placebo group; however, eNOS expression was significantly higher in the BPS group than in the placebo group. CONCLUSION: Prophylactic administration of BPS is useful for suppressing the development of SOS through the protective effects of LSEC.

Prospective analysis of the efficacy of beraprost sodium combined with alprostadil on diabetic nephropathy and influence on rennin-angiotensin system and TNF-α.

Efficacy of beraprost sodium (BPS) combined with alprostadil on diabetic nephropathy (DN) and its influence on renin angiotensin system (RAS) and TNF-α were investigated. One hundred and two patients with type 2 diabetic nephropathy admitted to Weifang People's Hospital from July 2017 to January 2019 were selected and divided into two groups according to the treatment plan. Fifty patients with alprostadil were the control group and 52 patients with alprostadil combined with BPS were the combined group. Related indexes of fasting blood glucose, hemorheology, coagulation function, renal function, urine routine, liver function, renin angiotensin system and changes of TNF-α (ELISA) were observed, and the occurrence of adverse reactions of patients were recorded. The fasting blood glucose of patients in the two groups after treatment was lower than that before treatment (P<0.05). After treatment, blood viscosity, plasma viscosity and erythrocyte deformation exponent of patients in the two groups decreased (P<0.05), and the combined group was lower than the control group (P<0.05). After treatment, the average volume of fibrinogen (FIB), D dimer and platelets of the patients in the two groups decreased (P<0.05), and the combined group was lower than the control group (P<0.05). After treatment, UACR, CysC, ß2-MG and α1-MG of patients decreased in the two groups (P<0.05), and the combined group was lower than the control group (P<0.05). After treatment, renin and angiotensin II of patients decreased in both groups (P<0.05). TNF-α of patients in both groups decreased after treatment (P<0.05), and the combined group was lower than the control group (P<0.05). In conclusion, compared with alprostadil, BPS combined with alprostadil can effectively improve hemodynamics, coagulation function and renal function of DN patients, and inhibit expression of RAS-related factors and TNF-α, which is a more effective method for DN treatment.

Beraprost Upregulates KV Channel Expression and Function via EP4 Receptor in Pulmonary Artery Smooth Muscle Cells Obtained from Rats with Hypoxia-Induced Pulmonary Hypertension.

The reduced expression and function of voltage-dependent potassium (KV) channels have been involved in the pathogenesis of hypoxia-induced pulmonary hypertension (HPH), leading to pulmonary vasoconstriction and vascular remodeling, while the upregulation of KV channels is of therapeutic significance for pulmonary hypertension. Beraprost sodium (BPS) has been shown to be effective in patients with pulmonary hypertension. However, the effect of BPS on O2-sensitive KV channels in pulmonary artery smooth muscle cells (PASMCs) remains unclear. In the present study, the effect of BPS on rats with HPH was observed, and the influence of BPS on the expression and function of O2-sensitive KV channels in PASMCs was investigated. The results revealed that BPS reduced mean pulmonary artery pressure, suppressed right ventricular hypertrophy, and attenuated the remodeling of pulmonary arteries in rats exposed to discontinuous hypoxia for 4 weeks (8 h/day). This was accompanied with the significantly upregulated expression of KV channel α-subunits (KV1.2, KV1.5 and KV2.1) and O2-sensitive voltage-gated K+ (KV) channel current (IK(V)) in small pulmonary arteries in HPH model rats, as well as in hypoxia-induced PASMCs. Furthermore, in vitrostudies have revealed that the upregulation of BPS on O2-sensitive KV channels was significantly inhibited after treatment with prostaglandin E2 receptor subtype EP4 antagonist GW627368X. Taken together, these results suggest that BPS attenuates the development of HPH through the upregulation of O2-sensitive KV channels, which was probably via the EP4 receptor-related pathway.

Beraprost sodium mitigates renal interstitial fibrosis through repairing renal microvessels.

Beraprost sodium (BPS), as a prostacyclin analog, plays a significant role in various diseases based on its antiplatelet and vasodilation functions. However, its regulation and role in chronic kidney disease (CKD) still remain elusive. Here, we determined whether BPS could alleviate renal interstitial fibrosis, and improve the renal function and its therapeutic mechanism. In vitro, BPS increased angiogenesis in the HUVECs incubated with BPS detected by tube formation assay and repair damaged endothelial cell-cell junctions induced by hypoxia. In vivo, mice were randomly assigned to a sham-operation group (sham), a unilateral ureteral obstruction group (UUO), and a BPS intragastrical administration group (BPS), and sacrificed at days 3 and 7 post-surgery (six in each group). In UUO model, tissue hypoxia, renal inflammation, oxidative stress, and fibrotic lesions were detected by q-PCR and Western blot techniques and peritubular capillaries (PTCs) injury was detected by a novel technique of fluorescent microangiography (FMA) and analyzed by MATLAB software. Meanwhile, we identified cells undergoing endothelial cell-to-myofibroblast transition by the coexpression of endothelial cell (CD31) and myofibroblast (a-SMA) markers in the obstructed kidney. In contrast, BPS protected against interstitial fibrosis and substantially reduced the number of endothelial cell-to-myofibroblast transition cells. In conclusion, our data indicate the potent therapeutic of BPS in mitigating fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT) progression after inhibiting inflammatory and oxidative stress effects. KEY MESSAGES: BPS could improve renal recovery through anti-inflammatory and anti-oxidative pathways. BPS could mitigate fibrosis through repairing renal microvessels and suppressing endothelial-mesenchymal transition (EndMT).

Beraprost sodium versus clopidogrel for preventing vascular thromboembolic events of arteriovenous fistula in uraemic patients: a retrospective study with a mean 3-year follow-up.

OBJECTIVE: This study aimed to evaluate the efficacy of beraprost sodium (BPS) or clopidogrel (CL) using vascular thromboembolic events (VTEs) of arteriovenous fistula as a primary endpoint in patients with end-stage renal disease (ESRD) undergoing arteriovenous fistula surgery. METHODS: We performed a multicentre, retrospective cohort study from August 2012 to August 2016. We studied patients with ESRD who underwent arteriovenous fistula surgery and received peroral administration of 40 µg BPS, three times per day, for 1 month, or 75 mg CL (initial dose of 300 mg), one time per day, for 1 month. The time to first on-study VTE was the primary endpoint. RESULTS: The BPS-treated cohort had a significantly delayed time to first VTE compared with the CL-treated cohort (hazard ratio 0.33, 95% confidence interval 0.18-0.56). An increased incidence of VTEs was detected in the 1-month follow-up, with rates of 2.4% and 8.7% for BPS and CL, respectively. This difference persisted over time, with rates of 8.0% and 18.1% at the final follow-up, respectively. CONCLUSION: CL-treated patients with ESRD have a greater risk of VTEs compared with BPS-treated patients. CL-treated patients also tend to experience a VTE within the first month after cessation of oral administration.

Therapeutic effect of valsartan combined beraprost sodium on hypertension complicated early renal in‐jury／ / 心血管康复医学杂志

To observe and analyze therapeutic effect of valsartan combined beraprost sodium on patients with hypertension (EH) complicated early renal injury (ERI).Methods : A total of 480 EH + ERI patients treated in our hospital in near two years were randomly and equally divided into valsartan group and combined treatment group (received valsartan combined beraprost sodium) , both groups were treated for three months .Levels of blood pressure , renal function related indexes were compared between two groups before and after treatment .Results :Compared with before treatment , after three months , there were significant reductions in levels of blood pressure , serum creatinine , urine β2 microglobulin and D‐dimer , and significant rise in creatinine clearance rate (Ccr) in two groups , P＝0.001 all.Compared with valsartan group after treatment , there were significant reductions in levels of blood pressure [ (130. 92 ± 5.92)／(80.18 ± 6.69) mmHg vs.(120. 93 ± 6. 53)／(69.98 ± 6.32) mmHg] , serum creatinine [ (93.92 ± 10. 49) μmol／L vs.(83. 14 ± 11. 03) μmol／L] , urine β2 microglobulin [ (385.41 ± 35.54) μg／L vs.(362.65 ± 26.59) μg／L] and D‐dimer [ (1. 75 ± 0.44) mg／L vs.(1. 01 ± 0.11) mg／L] , and significant rise in Ccr [ (63.22 ± 7. 66) ml／min vs.(79.13 ± 8.83) ml／min] in combined treatment group , P＝0.001 all.Conclusion :Compared with valsartan monotherapy , valsartan combined beraprost sodium can more significantly reduce blood pressure and protect renal function in hypertensive patients with early renal injury .

Beraprost sodium preconditioning prevents inflammation, apoptosis, and autophagy during hepatic ischemia-reperfusion injury in mice via the P38 and JNK pathways.

OBJECTIVE: The goal of this study was to determine the effects of beraprost sodium (BPS) preconditioning on hepatic ischemia-reperfusion (IR) injury and its underlying mechanisms of action. MATERIALS AND METHODS: Mice were randomly divided into sham, IR, IR+BPS (50 µg/kg), and IR+BPS (100 µg/kg) groups. Saline or BPS was given to the mice by daily gavage for 1 week before the hepatic IR model was established. Liver tissues and orbital blood were collected at 2, 8, and 24 hours after reperfusion for the determination of liver enzymes, inflammatory mediators, apoptosis- and autophagy-related proteins, key proteins in P38 and c-Jun N-terminal kinase (JNK) cascades, and evaluation of liver histopathology. RESULTS: BPS preconditioning effectively reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, improved pathological damage, ameliorated production of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß), and affected expressions of Bax, Bcl-2, Caspase-3, Caspase-8, and Caspase-9, microtubule-associated protein 1 light chain 3 (LC3), Beclin-1, and P62. The protective effects of BPS preconditioning were associated with reduced P38 and JNK phosphorylation. CONCLUSION: BPS preconditioning ameliorated hepatic IR injury by suppressing inflammation, apoptosis, and autophagy, partially via inhibiting activation of the P38 and JNK cascades.

Comparing the vascular thromboembolic events following arteriovenous fistula in Chinese population with end-stage renal diseases receiving Clopidogrel versus Beraprost sodium therapy: a retrospective cohort study.

BACKGROUND: To assess the time to first on-study vascular thromboembolic events (VTEs) of clopidogrel (CL) or beraprost sodium (BPS) in Chinese population with end-stage renal disease (ESRD) treated with arteriovenous fistula (AVF) surgery. METHODS: From Jan 2009 to May 2015, 346 ESRD cases suffering an AVF surgery and undergoing oral administration of 75 mg CL (initial dose of 300 mg), 1 time/day, for 4 weeks or 40 µg BPS, 3 times/day, for 4 weeks were retrospectively assessed. The primary outcome was time to first on-study VTE. RESULTS: In total, 222 ESRD cases (CL, n = 112; BPS, n = 110) were assessed, with a median follow-up time of 38.1 months (range, 37-40 months). The mean time to first on-study VTE was 1.2 weeks (0.5-2.3) and 1.8 weeks (1.2-3.8) for CL and BPS, respectively (HR 0.27, 95% CI 0.16-1.45; P = 0.00). An increased incidence of VTEs was found during the 1th-month follow-up, with rates of 14.2 and 5.5% for CL and BPS, respectively (P = 0.03). The difference persisted over time, with rates of 24.1 and 11.8% at final follow-up, respectively (P = 0.02). CONCLUSION: CL with an increased risk of VTEs tended to have a VTE within the 1st month after cessation compared with BPS.

Beraprost Sodium, a Stable Analogue of PGI2, Inhibits the Renin-Angiotensin System in the Renal Tissues of Rats with Chronic Renal Failure.

BACKGROUND/AIMS: Chronic renal failure (CRF) is a prolonged kidney condition characterized by decreased kidney function that can eventually develop into total kidney failure. The renin-angiotensin system (RAS) helps to regulate the balance between human bodily fluids and electrolytes. The aim of the present study was to investigate the effects of a prostacyclin analogue (beraprost sodium [BPS]) on the expression of key factors associated with local RAS activities in the renal tissues of rats with CRF. METHODS: After a CRF rat model was successfully established, the levels of BUN, SCr, phosphorus, and calcium were detected by an automatic biochemistry analyzer. Furthermore, the activities of malondialdehyde (MDA) and superoxide dismutase (SOD) in rat renal tissues were measured using a colorimetric method, while the activity of angiotensin-converting enzyme (ACE) was determined by ultraviolet (UV) spectrophotometry. In situ hybridization was employed to determine the expression of angiotensin II type 1 receptor (AT). Finally, the positive expression rates of cells expressing important apoptotic proteins (Bax and Bcl-2) were determined, and the protein and mRNA levels of phosphatidylinositol 3-kinase (AKT) and key factors involved in the RAS (AT1, AT2, angiotensin ACE and angiotensinogen [AGT]) were evaluated by RT-qPCR and western blot analysis. RESULTS: Initial observations revealed that treatment with BPS decreased the levels of BUN, SCr and phosphorus but increased calcium levels in the renal tissues of CRF rats. Additionally, BPS reduced the levels of MDA while increasing the levels of SOD, ACE activity, and AT1 expression in the renal tissues of CRF rats. BPS inhibited glomerular hypertension and hyperfiltration; increased the mRNA and protein levels of AKT and AT2; and decreased the mRNA and protein levels of AT1, AGT, and ACE in the renal tissues of CRF rats. CONCLUSION: The results of this study demonstrate that BPS, a PGI2 analogue, inhibits the expression of key factors involved in the local RAS, resulting in a delay in the occurrence and development of CRF. The key findings of the present study ultimately highlight the potential of this PGI2 analogue as a promising therapeutic strategy for treating CRF.

Ameliorative Effect of Beraprost Sodium on Celecoxib Induced Cardiotoxicity in Rats.

Selective COX-2 inhibitors are most widely used analgesic and anti-inflammatory drugs; however, its maximal use is highly associated with various serious abnormal cardiovascular events. Beraprost sodium (BPS), prostacyclin analogue has been shown to vasodilatory, antiplatelates, anti-inflmmatory, and antioxidant activity. The objective of the present study was to evaluate the effect of BPS on celecoxib cardiotoxicity in rats. Toxicity was induced in male Albino rats (250-280 g) by celecoxib (100 mg/kg/day). BPS (30 µg/kg/day) was administered alone and in combination with celecoxib for 14 days and various biochemicals, hemodynamic, left ventricular, biochemical, and histopathological parameters were studied. Cardiotoxicity of celecoxib was revealed by a significant increase in serum lactate dehydrogenase (LDH), troponin-T (Tn-T), tumor necrosis factor-α (TNF- α), creatine kinase-MB (CK-MB) and systolic blood pressure (SBP), left ventricular end diastolic pressure (LVEDP), LV (dp/dt)max, and LV (dp/dt)min as well as tissue thiobarbituric acid reactive substance (TBARS) and a significant decrease in tissue reduced glutathione (GSH). However, treatment with BPS reversed these alteration in LDH, Tn-T, TNF-α, CK-MB, SBP, LVEDP, LV (dp/dt)max, LV (dp/dt)min, TBARS and GSH levels. The histopathological study in cardiac left ventricle revealed protection of myocardium as manifested reduction of fibrosis by abolition of collagen deposition when celecoxib was combined with beraprost sodium. It could be concluded that beraprost sodium may prove a useful adjunct in patients being prescribed celecoxib.