Reports : Sulodexide inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy

( Hyoung Jo ),( Sang Hoon Jung ),( Jun Kang ),( Hye Bin Yim ),( Kui Dong Kang ) 생화학분자생물학회 2014 BMB Reports Vol.47 No.11

Sulodexide is a mixed glycosaminoglycan composed of heparin and dermatan sulfate. In this study, the anti-angiogenic effect of sulodexide was investigated using an oxygen-induced retinopathy (OIR) mouse model. The retinas of sham-injected OIR mice (P17) had a distinctive central area of nonperfusion, and this area was significantly decreased in sulodexide-injected mice. The number of neovascular tufts measured by SWIFT_NV and mean neovascular lumen number were significantly decreased in sulodexide-injected mice. Hyperbaric oxygen exposure resulted in increased levels of VEGF, MMP-2 and MMP-9, and when mice were treated with sulodexide, a dose-dependent reduction in VEGF, MMP-2 and MMP-9 levels was observed. Our results clearly demonstrate the anti-angiogenic effect of sulodexide and highlight sulodexide as a candidate supplementary substance to be used for the treatment of ocular pathologies that involve neovascularization. [BMB Reports 2014; 47(11): 637-642]

Sulodexide 유발 고칼륨 혈증: 증례 보고

박인일 ( In Il Park ),최명진 ( Myung Jin Choi ),윤종우 ( Jong Woo Yoon ),김수진 ( Soo Jin Kim ),박태진 ( Tae Jin Park ),송영수 ( Young Soo Song ),이영기 ( Young Ki Lee ),김형직 ( Hyung Jik Kim ),노정우 ( Jung Woo Noh ),구자룡 ( Ja 대한신장학회 2009 Kidney Research and Clinical Practice Vol.28 No.3

Sulodexide is composed of two glycosaminoglycans (fast-moving heparin 80%, dermatan sulfate 20%) that are capable of preventing diabetic nephropathy by correcting abnormal glycosaminoglycan metabolism. Considering heparin-like propertyof sulodexide, side effect profiles of sulodexide are expected to be similar with those of heparin. Among those side effects, we remarked on heparin-induced hyperkalemia and hereby report a case of severe hyperkalemia during the use of sulodexide. A 52-year-old man with diabetic nephroapthy and hypertension was admitted to our hospital because of severe hyperkalemia up to 7.5 meq/L. His clinical condition was stable and medications including losartan and furosemide had not been changed for last 6 months except the addition of sulodexide, which was started 30 days prior to admission. Despite intensive use of Kayexalate and immediate discontinuation of losartan, hyperkalemia aggravated up to 8.0 meq/L. After recognition of possible sulodexide-induced hyperkalemia, sulodexide was discontinued, which resulted in rapid correction of hyperkalemia. In view of the above discussed clinical consideration, we suspect sulodexide as a major cause of hyperkalmia and report this case with a review of literature.

당뇨망막병증 환자에서 설로덱시드 복용 후 황반하 맥락막두께의 종적인 장기 변화

차창민,임재완,김창주,이승욱,이상준 대한안과학회 2023 대한안과학회지 Vol.64 No.12

목적: 당뇨망막병증 환자에서 설로덱시드(sulodexide) 복용 후 황반하 맥락막두께의 2년 장기 변화를 종단면적으로 알아보았다. 대상과 방법: 당뇨망막병증 환자에서 설로덱시드 복용 후 2년 이상 경과 관찰한 38안을 대상으로 설로덱시드 복용 전, 복용 후 6개월, 12개월, 24개월의 중심망막두께, 황반하 맥락막두께, 맥락막혈관지수(choroidal vascularity index)를 각각 비교하고 전향적 코호트방식으로 분석하였다. 결과: 전체 환자군에서 설로덱시드 복용 전 황반하 맥락막두께는 216.00 ± 64.23 μm였다. 황반하 맥락막두께는 복용 후 6개월, 12개월, 24개월에 각각 223.87 ± 62.18 μm, 225.53 ± 62.02 μm, 225.76 ± 63.62 μm로 유의한 증가가 있었다(p=0.0377, p=0.0159, p=0.0135). 설로덱시드 복용 전 중심망막두께는 318.14 ± 102.28 μm였다. 중심망막두께는 복용 후 6개월 313.08 ± 77.47 μm, 12개월 314.97 ± 88.32 μm, 24개월 320.03 ± 97.36 μm로 유의한 증가는 없었다(p=0.904, p=0.736, p=0.892). 결론: 설로덱시드 복용 후 2년간 경과 관찰 결과 황반하 맥락막두께는 복용 이후 2년까지 유의하게 증가하였다. 이러한 맥락막두께의증가는 중심황반두께와는 관련이 없었다. Purpose: To evaluate the two-year longitudinal changes in subfoveal choroidal thickness (CT) following sulodexide treatment in patients with diabetic retinopathy. Methods: Thirty-eight eyes from patients with diabetic retinopathy, followed for a minimum of two years after sulodexide administration, were included. Subfoveal CT, measured using optical coherence tomography, was analyzed prospectively. Variables including age, sex, duration of diabetes mellitus, HbA1c, blood pressure, sulodexide treatment duration, refractive error, axial length, central macular thickness (CMT), visual acuity, laser photocoagulation, and intravitreal anti-vascular endothelial growth factor injections were evaluated for potential effects on CT. CMT, subfoveal CT, and choroidal vascularity index were compared at baseline and at 6, 12, and 24 months after sulodexide. Results: Of the 38 eyes, 10 belonged to males and 28 to females. The mean data were as follows: age, 67.18 ± 8.87 years; duration of diabetes, 18.11 ± 7.57 years; HbA1c, 8.76 ± 1.60 mmol/L; systolic blood pressure, 134.69 ± 14.68 mmHg; diastolic blood pressure, 73.72 ± 11.90 mmHg; duration of sulodexide, 25.79 ± 3.17 months; refractive error, 0.22 ± 2.19 diopters (D); and axial length, 23.32 ± 0.89 mm. During the observation period, 15 eyes underwent laser photocoagulation and 17 eyes received intravitreal anti-vascular endothelial growth factor injections. The mean subfoveal CT was 216.00 ± 64.23 μm before sulodexide administration and increased to 223.87 ± 62.18 μm, 225.53 ± 62.02 μm, and 225.76 ± 63.62 μm at 6, 12, and 24 months, respectively (p = 0.0377, p = 0.0159, p = 0.0135). The CMT was 318.14 ± 102.28 μm initially and changed to 313.08 ± 77.47 μm, 314.97 ± 88.32 μm, and 320.03 ± 97.36 μm at the aforementioned intervals, with no significant variation (p = 0.904, p = 0.736, p = 0.892). Conclusions: Sulodexide administration led to a significant rise in subfoveal CT over a 2-year follow-up. This change in CT was not mirrored in the CMT.

경피적 관동맥 풍선확장 성형술후 재협착에 관한 Sulodexide의 효과에 대한 전향적, 무작위 비교연구

김진우,이철환,정상식,강덕현,홍명기,송재관,김재중,박성욱,박승정 대한순환기학회 1997 Korean Circulation Journal Vol.27 No.6

Sulodexide prevents peripheral nerve damage in streptozotocin induced diabetic rats

Jin, Heung Yong,Lee, Kyung Ae,Song, Sun Kyung,Liu, Wei Jing,Choi, Ji Hae,Song, Chang Ho,Baek, Hong Sun,Park, Tae Sun Elsevier 2012 european journal of pharmacology Vol.674 No.2

<P><B>Abstract</B></P><P>We investigated whether sulodexide has additional protective effects against peripheral nerve damage caused by microvascular dysfunction in a rat model of diabetes. Female Sprague–Dawley (SD) rats were divided into the following 4 groups (n=7–9/group): Normal, Normal+Sulodexide (sulodexide 10mg/kg), diabetic group, and diabetic+Sulodexide (sulodexide 10mg/kg). We assessed current perception threshold, skin blood flow, superoxide dismutase, and proteinuria in experimental rats after oral administration of sulodexide for 20weeks. We also performed morphometric analysis of sciatic nerves and intraepidermal nerve fibers of the foot. Superoxide dismutase activity in the blood and sciatic nerve were increased significantly after sulodexide treatment in the diabetic group. Current perception threshold was reduced at 2000Hz (633.3±24.15 vs 741.2±23.5μA, <I>P</I><0.05) and skin blood flow was improved (10.90±0.67 vs 8.85±0.49TPU, <I>P</I><0.05) in the diabetic+Sulodexide group compared with the diabetic group. The mean myelinated axon area was significantly larger (56.6±2.2 vs 49.8±2.7μm<SUP>2</SUP>, <I>P</I><0.05) and the intraepidermal nerve fiber density was significantly less reduced (6.27±0.24 vs 5.40±0.25/mm, <I>P</I><0.05) in the diabetic+Sulodexide group compared to the diabetic group. Our results demonstrate that sulodexide exhibits protective effects against peripheral nerve damage in a rat experimental model of diabetes. Therefore, these findings suggest that sulodexide is a potential new therapeutic agent for diabetic peripheral neuropathy.</P> <P><B>Highlights</B></P><P>► Sulodexide prevented diverse peripheral nerve degeneration. ► Sulodexide alleviated the increased thresholds in response of sine-wave stimuli. ► The neuroprotection from sulodexide attributed to improved oxidative stresses. ► Sulodexide is a promising novel therapeutic agent for diabetic peripheral neuropathy.</P>

Anti-Proteinuric Effect of Sulodexide in Immunoglobulin A Nephropathy

방기태,오국환,진호준,채동완,주권욱,김연수,김성권,주경돈,김화정,안규리 연세대학교의과대학 2011 Yonsei medical journal Vol.52 No.4

Purpose: We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy. Materials and Methods: A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value. Results: At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38±0.77 at baseline to 5.98±0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not. Conclusion: A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.

Use of low-dose sulodexide in IgA nephropathy patients on renin-angiotensin system blockades

( Byeong Yun Yang ),( Hee Seon Lee ),( Sang Heon Song ),( Ihm Soo Kwak ),( Soo Bong Lee ),( Dong Won Lee ),( Eun Young Seong ) 대한신장학회 2012 Kidney Research and Clinical Practice Vol.31 No.3

Background: Despite using renin-angiotensin system (RAS) blockades, some of the patients with immunoglobulin A (IgA) nephropathy often had persistent proteinuria of more than 500 mg/d. They need to be managed further by alternative methods to halt the progression of the disease; these methods could also be applied safely over a long period of time. In this context, sulodexide has been studied for the management of diabetic nephropathy. Methods: A retrospective review was carried out involving 20 patients with IgA nephropathy who had been taking sulodexide (50 mg daily) as an add-on therapy together with an optimal dose of RAS blockades during 2008-2009. We evaluated the proteinuria reduction rates and renal function changes. Results: During 11.1±72.7 months of follow-up duration, urinary protein-to- creatinine ratio(UPCR) decreased for 1.57±0.6 to1.17±0.7 g/g (P=0.032). Twenty-five percent of the patients showed a greater than 50% reduction of UPCR, and 40% had a UPCR of less than 1.0 g/g at their final observations. The analysis of the factors contributing to the effect found that a higher pretreatment UPCR showed a significant correlation with the UPCR decrease (r=0.45, P=0.047). Neither the adverse effects nor the renal function impairments were documented during the management. Conclusion: Low-dose sulodexide has an additional modest antiproteinuric effect on IgA nephropathy undergoing RAS blockade therapy.

A Case of Livedoid Vasculopathy Successfully Treated with Sulodexide

( Chang Hwa Song ),( Dong Seok Shin ),( Ju Wang Jang ),( Tae Lim Kim ),( Young Gyun Kim ),( Joung Soo Kim ),( Hyun-min Seo ) 대한피부과학회 2020 Annals of Dermatology Vol.32 No.6

We report a 29-year-old female with a one-month history of non-healing multiple erythematous to violaceous plaques with crusts over both legs and feet. Tender, scarring ulcers with surrounding erythema were present. The clinical manifestation, together with histopathologic findings of fibrinoid plugs within vascular lumens and walls, as well as red blood cell extravasation, led to diagnosis of livedoid vasculopathy. The patient experienced recurrent painful violaceous plaques with ulcerations during the two years of treatment with oral pentoxifylline 400 mg three times daily. The cutaneous lesions and symptoms dramatically improved after the treatment regimen changed to oral sulodexide (250 lipasemic units) three times daily. Sulodexide, a highly purified mixture of glycosaminoglycans including dermatan sulfate and lowmolecular weight heparin, could be an effective therapy for recalcitrant livedoid vasculopathy. Herein, we report a case of livedoid vasculopathy treated with sulodexide, which has not previously been reported. (Ann Dermatol 32(6) 508∼511, 2020)

Simplified Analysis of Lipoprotein Lipase Activity: Evaluation of Lipasemic Activity of Low Molecular Weight Heparin in Rats

지준필,Chong-Kook Kim,Seung-Hyun Nam,박유미,이효종,박요한,맹한주 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

A simple procedure for measuring lipoprotein lipase activity was developed by using newly formulated substrate with turbidimetry method. The activity of lipoprotein lipase was expressed as Yvalue (%) that was calculated by measuring UV absorbance (600 nm) at two time points (30 sec and 15 min). Lipid emulsions as the substrate and other factors affecting the lipolytic activity of lipase were studied. The optimal conditions for an in vitro experiment were found to be with LIPOMCT® as lipid substrate at 37oC in tris-HCl buffer (pH 7.4) in the presence of BSA. To evaluate an in vivo applicability, low molecular weight heparin (LMWH)-containing drug, Sulodexide®, was administered to the rats. The serum from LMWH-administered rats was incubated in an optimized analytical condition without BSA. As expected, increasing the amount of LMWH administered led to higher lipase activity. The newly developed method was successfully applied to an in vivo model suggesting the potential to be applicable for the pharmacodynamic studies of commercially available products of LPL analogues in human subjects, and for the diagnosis of acute pancreatitis in the clinical laboratory.

Perioperative implication of the endothelial glycocalyx

송종욱,Michael S. Goligorsky 대한마취통증의학회 2018 Korean Journal of Anesthesiology Vol.71 No.2

The endothelial glycocalyx (EG) is a gel-like layer lining the luminal surface of healthy vascular endothelium. Recently, the EG has gained extensive interest as a crucial regulator of endothelial funtction, including vascular permeability, mechanotransduction, and the interaction between endothelial and circulating blood cells. The EG is degraded by various enzymes and reactive oxygen species upon pro-inflammatory stimulus. Ischemia-reperfusion injury, oxidative stress, hypervolemia, and systemic inflammatory response are responsible for perioperative EG degradation. Perioperative damage of the EG has also been demonstrated, especially in cardiac surgery. However, the protection of the EG and its association with perioperative morbidity needs to be elucidated in future studies. In this review, the present knowledge about EG and its perioperative implication is discussed from an anesthesiologist’s perspective.