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Objective. To analyze the clinical effect of prescription used for invigorating spleen, reinforcing kidney and warming yang combined with calcium dobesilate to treat senile diabetic nephropathy (DN). Methods. The clinical data of 110 elderly patients with DN in our hospital from November 2020 to November 2021 were selected for retrospective analysis, and they were divided into the observation group (OG, n = 55) and the control group (CG, n = 55) according to the principle of random grouping. The CG received conventional therapy and calcium dobesilate, and the OG received conventional therapy, calcium dobesilate and prescription used for invigorating spleen, reinforcing kidney and warming yang to evaluate the clinical value of different treatment programs by comparing their clinical indicators after treatment. Results. The total effective rate of clinical treatment in the OG was clearly higher than the CG (P < 0.05). The blood glucose indexes, and the levels of ALB and RBP in the OG were visibly lower than the CG after treatment (P < 0.001). After treatment, the average levels of BUN and Cr in the OG were visibly lower than the CG (P < 0.001), while the average eGFR level was significantly higher than the CG (P < 0.001). Conclusion. The prescription used for invigorating spleen, reinforcing kidney and warming yang combined with calcium dobesilate is a reliable method to improve the hemorheology indexes and renal function of DN patients, which benefits patients, and further studies are helpful to establish a better solution for such patients. [ABSTRACT FROM AUTHOR]

The letter published in Clinical Chemistry & Laboratory Medicine addresses the negative interference of calcium dobesilate in the Roche sarcosine oxidase creatinine assay. The study aims to correct this interference through a redox reaction using CuO as an oxidant. The research found that CuO effectively corrected the interference of calcium dobesilate on creatinine detection, ensuring bias levels remained below 6%. This cost-effective method may have broader applications beyond creatinine assays and could be beneficial for other Trinder test methods in the future. [Extracted from the article]

This prospective, observational, multicenter study assessed the tolerance of Dobenox Forte®, the first approved over-the-counter product containing calcium dobesilate, in 1795 outpatients with chronic venous disease (CVD) in daily clinical practice. In addition, the effectiveness (decrease in circumferences of a more affected limb at the ankle and middle part of the calf, and changes in the severity of CVD signs) was assessed. No adverse events related to use of the preparation were reported in a period of 64 ± 20 days. Dobenox Forte® use was associated with a reduction in calf circumference by 13.1 mm (95%CI: 12.2–14.1) and in ankle circumference by 9.7 mm (95%CI: 9.2–11.0) in patients reporting swelling of the lower legs (60.0% of the cohort). A reduction in calf and ankle circumference by at least 1 cm was achieved in 34.9% and 24.9% of patients, respectively. The percentages of patients reporting moderate to very severe lower limb heaviness decreased from 96.6% to 56.0%, calf cramps decreased from 91.0% to 41.0%, calf pain decreased from 89.2% to 43.7%, swelling decreased from 86.1% to 38.8%, and burning sensation that worsens when standing decreased from 79.0% to 33.7%. The medicinal product Dobenox Forte® is well tolerated by patients and seems to effectively reduce the symptoms of CVD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of a combination therapy involving calcium dobesilate and candesartan in the treatment of proliferative diabetic retinopathy and its impact on the transforming growth factor b1 (TGF-b1), vascular endothelial growth factor (VEGF) and interleukin-19 (IL-19) levels in the vitreous humor. Methods: Between January 2020 and May 2023, 112 patients with proliferative diabetic retinopathy from Handan City Eye Hospital, China were enrolled in this study. They were divided into two groups: study group (n = 56) - orally administered 500 mg of calcium dobesilate combined with 50 mg of candesartan daily - and control group (n = 56), received calcium dobesilate only. Patients began treatment with calcium dobesilate and candesartan as soon as diabetic retinopathy was diagnosed. Treatment efficacy, changes in hemorrhage area, macular thickness and best-corrected visual acuity were assessed before and after treatment (for a duration of 60 days). Results: Study group had significantly higher (p < 0.05) treatment efficacy compared to control group, achieving a total effective rate of 92.86 %. It also exhibited reduced hemorrhage area and macular thickness, which were significantly lower (p < 0.05) than those in control group. Best-corrected visual acuity was significantly higher in the study group (p < 0.05) followed by improved peak systolic velocity and end-diastolic velocity after treatment (p < 0.05). Additionally, TGF-b1, VEGF and IL-19 levels in the vitreous humor were significantly lower in study group compared to control group (p < 0.05). Conclusion: The combination of calcium dobesilate and candesartan demonstrates significant therapeutic efficacy in treating proliferative diabetic retinopathy while reducing the TGF-b1, VEGF and IL-19 levels in the vitreous humor. Large-scale studies are needed to validate these findings and delve into treatment mechanisms and long-term effects. [ABSTRACT FROM AUTHOR]

Objectives: Chinese patent medicines (CPMs) are commonly prescribed by clinicians in China as adjuvant therapy for diabetic retinopathy (DR). The study of network meta-analysis (NMA) aims to compare the effectiveness and safety of three CPMs plus calcium dobesilate (CD) for DR, and to explore optimal CPM for treatment of DR. Methods. Bayesian network meta-analyses were designed to evaluate the safety and effectiveness of different CPMs for the treatment of DR. Systematic Review Registration CRD42022323996. Results. A total of 23 eligible RCTs involving 1824 patients were enrolled. Compared with CD alone, Cmpound Danshen Dripping Pills (DS) + CD or Qiming Granule (QM) + CD considerably enhanced best corrected visual acuity (BCVA); DS + CD or Compound Xueshuantong Capsule (XST) + CD significantly reduced macular thickness; CPMs + CD significantly reduced the level of VEGF. In addition, DS + CD or XST + CD over QM + CD in reducing macular thickness. As for the adverse events, the differences across different CPMs were not statistically significant, and no statistically significant difference between the CPMs and CD. Conclusion. DS plus CD or QM plus CD may be better effective in improving BCVA; DS plus CD or XST plus CD may be better effective in reducing macular thickness; The combination therapy all may be better effective in reducing the level of VEGF. As for safety profile that CPMs plus CD did not increase the incidence of adverse events. The results of this study might support DS as a relatively prior adjuvant therapy option for patients with DR.

Calcium dobesilate (CD) is a synthetic venoactive drug used in veterinary medicine to treat equine navicular disease. Etamsylate is a haemostatic agent used in horses for the treatment of exercise‐induced pulmonary haemorrhage. Both etamsylate and CD dissociate in the circulatory system with 2,5‐HBSA as the active drug. The aim of the research was to be able to provide detection time (DT) advice from pharmacokinetic (PK) studies in Thoroughbred horses to better inform trainers, and their veterinary surgeons, prescribing these substances for treatment of Thoroughbred racehorses. Two (pilot study) and six (final study) horses were given 28 and 9 repeated dose of CD (3 mg/kg BID) respectively. Two horses were each given a single intravenous (IV) dose of etamsylate (10 mg/kg). Plasma and urine 2,5‐HBSA concentrations were measured by liquid chromatography–tandem mass spectrometry (LC–MS/MS). The CD pilot study revealed that steady state could be reached with a few days and that 2,5‐HBSA in plasma and urine shows instability during storage at −20°C but appears stable at −80°C. A novel holistic non‐linear mixed‐effects three‐compartmental PK model was developed that described both plasma and urine concentrations of 2,5‐HBSA, from either CD or etamsylate administration. Typical values for 2,5‐HBSA clearance and bioavailability were 2.0 mL/min/kg and 28% respectively. Using the parameters obtained from this PK model, in conjunction with methodology developed by Toutain, afforded a possible screening limit (SL) that can regulate for a DT of 3 days in urine; however, a corresponding SL in plasma would be below current levels of detection. However, it is the responsibility of the individual racing authorities to apply their own risk management with regard to SLs and DTs. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of telmisartan combined with calcium dobesilate on hyperten⁃ sive patients with type 2 diabetes mellitus (T2DM) on the blood pressure rhythm. Methods Patients with hyper⁃ tension and T2DM who were treated in Hengshui people′s Hospital from January 2021 to December 2022 were selected as the study subjects. According to the principle of random grouping, the patients were divided into the control group (n = 115) and the observation group (n = 113) . Patients in the control group were treated with telmisartan (40 mg once daily), while the patients in the observation group received additional calcium dobesilate treatment (0.5 g three times daily) on the basis of the treatment in the control group. Both groups of patients were treated for 12 months with follow-up visits every 3 months. The blood pressure indicators including 24-hour average systolic blood pressure (24 h SBP),24-hour average diastolic blood pressure (24 h DBP),24-hour average pulse pressure (24 h PP), daytime average systolic blood pressure (dSBP), daytime average diastolic blood pressure (dDBP), daytime average pulse pressure (dPP), nighttime average systolic blood pressure (nSBP), nighttime average diastolic blood pressure (nDBP) and nighttime average pulse pressure (nPP) ； blood glucose indicators including fasting blood glucose (FBG),2-hour postprandial blood glucose (2 h PG) and glycosylated hemoglobin (HBA1c) ； endothelial function indicators including endothelin-1(ET-1), nitric oxide (NO) and vascular endo⁃ thelial growth factor (VEGF) ； and occurrence of adverse reactions during the medication period were statistically analyzed for both groups of patients. Results Before treatment, there were no statistically significant differences (P > 0.05) in the various indicators (blood pressure, blood glucose, endothelial function) between the two groups of patients. After 3,6, and 12 months of treatment, the blood pressure indicators (24 h SBP,24 h DBP,24 h PP, dSBP, dDBP, dPP, nSBP, nDBP, nPP), blood glucose indicators (FBG,2 hPG, HBA1c), and endothelial function indicators (ET-1) were significantly lower than before treatment in both groups of patients, and the levels of these above-mentioned indicators in the observation group were lower than those in the control group, with statis⁃ tically significant differences (P < 0.05) . The levels of NO and VEGF in both groups of patients were significantly higher than before treatment, and the levels of NO and VEGF in the observation group were higher than those in the control group, with statistically significant differences (P < 0.05) . The incidence of adverse reactions during the medication period showed no statistically significant differences between the two groups of patients (P > 0.05) . Conclusion The combination of telmisartan combined with calcium dobesilate reduces blood pressure levels, regulates blood pressure rhythm, and improves endothelial function in patients with hypertension and T2DM, and shows favorable safety. [ABSTRACT FROM AUTHOR]

Background: To explore the effect of calcium dobesilate combined with hypoglycemic drugs in the treatment of cataract complicated with non-proliferative diabetic retinopathy (NPDR) and its effects on fundus microcirculation, intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein 1 (MCP-1), and macrophage migration inhibitory factor (MIF). Mathods: From March 2019 to January 2021, a total of 114 patients with cataract and NPDR were included, and the patients were assigned into the control and the observation groups by random number table method, with 57 cases/group. The control was given hypoglycemic drugs, and the observation was given calcium dobesilate combined therapy. The therapeutic efficacy, blood glucose and blood lipid levels, fluorescein fundus angiography results, fundus microcirculation indexes, retinal neovascularization- related factors, and ICAM-1, MCP-1, and MIF levels before and after treatment were compared between the two groups. Results: The total effective rate of treatment in the observation was higher vs. the control (P < 0.05); Fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL) in the observation after treatment were reduced vs. the control (P < 0.05); The number of micro-hemangiomas in the observation after treatment was less vs. the control, and the area of hemorrhage, the area of exudation and the thickness of the yellow plate were smaller vs. the control (P < 0.05); The resistance index (Rl) value of the observation after treatment was lower than the control, and the end-diastolic blood flow velocity (EDV) and the peak systolic blood flow velocity (PSV) of the observation were higher vs. the control (P < 0.05). ICAM-1, MCP-1, MIF, vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF- 1) in the observation after treatment were reduced vs. the control, but pigment epithelium-derived factor (PEDF) were higher vs. the control (P < 0.05); one case of gastrointestinal reaction took place in the observation, but no adverse reaction occurred in the control, and no clear difference exhibited in the incidence of adverse reactions between the two groups (P > 0.05). Conclusions: Calcium dobesilate combined with hypoglycemic drugs has good clinical efficacy in the treatment of cataract complicated with NPDR, which can effectively reduce the level of blood glucose and blood lipids, reduce inflammation, and mitigate the microcirculation of branch retinal vein occlusion lesions. [ABSTRACT FROM AUTHOR]

Background: To explore the effect of calcium dobesilate combined with hypoglycemic drugs in the treatment of cataract complicated with non-proliferative diabetic retinopathy (NPDR) and its effects on fundus microcirculation, intercellular adhesion molecule 1 (ICAM-1), mono - cyte chemoattractant protein 1 (MCP-1), and macrophage migration inhibitory factor (MIF). Methods: From March 2019 to January 2021, a total of 114 patients with cataract and NPDR were included, and the patients were assigned into the control and the observation groups by random number table method, with 57 cases/group. The control was given hypoglycemic drugs, and the observation was given calcium dobesilate combined therapy. The therapeutic efficacy, blood glucose and blood lipid levels, fluorescein fundus angiography results, fundus microcirculation indexes, retinal neovascularizationrelated factors, and ICAM-1, MCP-1, and MIF levels before and after treatment were compared between the two groups. Results: The total effective rate of treatment in the observation was higher vs. the control (P < 0.05); Fasting blood glucose (FBG), 2 h postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC) and low density lipoprotein (LDL) in the observation after treatment were reduced vs. the control (P < 0.05); The number of micro-hemangiomas in the observation after treatment was less vs. the control, and the area of hemorrhage, the area of exudation and the thickness of the yellow plate were smaller vs. the control (P < 0.05); The resistance index (RI) value of the observation after treatment was lower than the control, and the end-diastolic blood flow velocity (EDV) and the peak systolic blood flow velocity (PSV) of the observation were higher vs. the control (P < 0.05). ICAM-1, MCP-1, MIF, vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF1) in the observation after treatment were reduced vs. the control, but pigment epithelium-derived factor (PEDF) were higher vs. the control (P < 0.05); one case of gastrointestinal reaction took place in the observation, but no adverse reaction occurred in the control, and no clear difference exhibited in the incidence of adverse reactions between the two groups (P > 0.05). Conclusions: Calcium dobesilate combined with hypoglycemic drugs has good clinical efficacy in the treatment of cataract complicated with NPDR, which can effectively reduce the level of blood glucose and blood lipids, reduce inflammation, and mitigate the microcirculation of branch retinal vein occlusion lesions.

Cerebral stroke is a serious clinical condition in which oxidative stress, inflammation, necrosis, apoptosis, and autophagy play important roles in its pathogenesis. This study investigated the neuroprotective and healing effects of calcium dobesilate (CD) on cerebral hypoxia/reperfusion injury in rats. Forty Wistar albino male rats, each weighing 300–350 g, were separated into the Control group (no surgery and no pharmacological agent was administered); Sham-A group (only surgery was performed); DBL-A group (surgery was performed and CD 100 mg/kg/day was administered intraperitoneally for 3 days); Sham-C group (only surgery was performed); and DBL-C group (surgery was performed and 100 mg/kg/day CD was administered intraperitoneally for 10 days). Under sedation anesthesia, the bilateral common carotid arteries of all rats except the Control group were clipped for 30 min. After 4 h, the CD was given to the relevant groups, and then, all subjects were euthanized at scheduled times. The brain of each animal was removed for histopathological (hematoxylin and eosin staining), immunohistochemical (beclin-1, anti-MHC class II and anti-CD-68 staining), and biochemical (TNF, IL-1β, IL-6, caspase-3, GSH/GSSG, malondialdehyde, protein carbonyl, LC3II/LC3I, and beclin-1 levels) evaluations. It was observed that CD could reduce necrosis and mitigate polarization of microglia to the M1 phenotype, autophagy, free oxygen radicals, protein carbonylation, lipid peroxidation, IL-1β, IL6, TNF, caspase-3, beclin-1, and LC3II/LC3I levels in acute and chronic periods of hypoxia/reperfusion injury. From these results, it was observed that CD treatment could reduce neuronal necrosis and create anti-inflammatory, anti-edema, anti-oxidant, anti-apoptotic, and anti-autophagic effects in hypoxia/reperfusion injury in rats. [ABSTRACT FROM AUTHOR]

Background: Non-proliferative diabetic retinopathy (NPDR), a common diabetic complication with high morbidity, is featured by impaired visual function and fundus lesions. It has been reported that oral Chinese patent medicines (OCPMs) may improve visual acuity and fund signs. However, the best possible OCPMs for NPDR remain questionable and merit further investigation. Methods: From inception to October 20, 2022, seven databases were searched for eligible randomized controlled trials (RCTs). The outcomes were clinical effective rate, visual acuity, visual field gray value, microaneurysm volume, hemorrhage area, macular thickness, and adverse events rate. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the quality of the included studies. Network meta-analysis was performed using R 4.1.3 and STATA 15.0 software. Results: We included 42 RCTs with 4,858 patients (5,978 eyes). The Compound Danshen Dripping Pill (CDDP) combined with calcium dobesilate (CD) had the most improvement in clinical efficacy rate (SUCRA, 88.58%). The Compound Xueshuantong Capsule (CXC) combined with CD may be the best intervention (SUCRA, 98.51%) for the improvement of visual acuity. CDDP alone may be the most effective treatment option (SUCRA, 91.83%) for improving visual field gray value. The Hexuemingmu Tablet (HXMMT) and Shuangdan Mingmu Capsule (SDMMC) combined with CD may be the most effective treatment for reducing microaneurysm volume and hemorrhage area (SUCRA, 94.48%, and 86.24%), respectively. Referring to reducing macular thickness, CXC combined with CD ranked first (SUCRA, 86.23%). Moreover, all OCPMs did not cause serious adverse reactions. Conclusion: OCPMs are effective and safe for NPDR. CDDP alone, and combined with CD, may be the most effective in improving visual field gray value and clinical efficacy rate, respectively; CXC combined with CD may be the best in enhancing BCVA and reducing macular thickness; HXMMT and SDMMC combined with CD, maybe the most effective regarding microaneurysm volume and hemorrhage area, respectively. However, the reporting of methodology in the primary study is poor, potential biases may exist when synthesizing evidence and interpreting the results. The current findings need to be confirmed by more large-sample, double-blind, multi-center RCTs of rigorous design and robust methods in the future. [ABSTRACT FROM AUTHOR]

Objectives: Patients with superficial venous reflux disease admit to the outpatient clinics with a wide range of symptoms. Although none of the marketed medications disappear the varicosities, they are helpful to relieve the symptoms of the patients to a certain degree. We investigated the influence of the addition of magnesium oxide (MO) to the standard symptomatic treatment of patients with superficial venous reflux disease. Materials and Methods: Thirty-two consecutive patients who were diagnosed with chronic superficial venous reflux disease were randomly divided into 2 groups. The first group (n=16) was treated with a Horse chestnut seed extract (HCSE)-calcium dobesilate combined therapy, whereas the second group was treated with HCSE-calcium dobesilate combined plus MO therapy. Results: The scores of symptoms including mean burning sensation, heaviness, cramps, edema, restlessness on the affected leg, and visual analog scale improved significantly in the second group with additional MO uptake at the end of the 2-week treatment period (p<0.05). Conclusion: The addition of MO into the symptomatic treatment regime of patients is associated with a more efficient relief in symptoms and associated with a significant decrease in edema when combined with other anti-varicose vein agents. [ABSTRACT FROM AUTHOR]

This prospective, observational, multicenter study assessed the tolerance of Dobenox Forte®, the first approved over-the-counter product containing calcium dobesilate, in 1795 outpatients with chronic venous disease (CVD) in daily clinical practice. In addition, the effectiveness (decrease in circumferences of a more affected limb at the ankle and middle part of the calf, and changes in the severity of CVD signs) was assessed. No adverse events related to use of the preparation were reported in a period of 64 ± 20 days. Dobenox Forte® use was associated with a reduction in calf circumference by 13.1 mm (95%CI: 12.2–14.1) and in ankle circumference by 9.7 mm (95%CI: 9.2–11.0) in patients reporting swelling of the lower legs (60.0% of the cohort). A reduction in calf and ankle circumference by at least 1 cm was achieved in 34.9% and 24.9% of patients, respectively. The percentages of patients reporting moderate to very severe lower limb heaviness decreased from 96.6% to 56.0%, calf cramps decreased from 91.0% to 41.0%, calf pain decreased from 89.2% to 43.7%, swelling decreased from 86.1% to 38.8%, and burning sensation that worsens when standing decreased from 79.0% to 33.7%. The medicinal product Dobenox Forte® is well tolerated by patients and seems to effectively reduce the symptoms of CVD.

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This was a single-arm multi-centric study conducted to evaluate the efficacy and safety of the Sitcom Forte® tablet (Euphorbia prostrata 100 mg plus calcium dobesilate 500 mg) and Sitcom® cream (Euphorbia prostrata dry extract cream) in patients (≥ 18 years of age) with varicose veins. A total of 104 patients, with a mean age of 47.0 years, were enrolled. They were advised to take a fixed-dose combination of Euphorbia prostrata plus calcium dobesilate tablets twice daily for 1 month and further once or twice daily (as per condition) for the next 2 months and local application of cream twice daily for 3 months. At the 3-month follow-up, the mean score of pain in the leg, swelling, tingling, numbness, and itching improved significantly from baseline (mean change: − 2.9 [69.2%], − 2.0 [57.8%], − 2.0 [68.0%], − 2.0 [67.1%], and − 2.2 [74.1%], respectively; P = 0.0001). At follow-up, ulcers completely healed in 58.3% of patients, and > 90% experienced good-to-excellent treatment improvement as assessed by physicians. The treatment was efficacious and well tolerated in patients with varicose veins, which may be attributed to the multimodal mechanism of action of Euphorbia prostrata and calcium dobesilate in the multifactorial pathophysiology of the disease. [ABSTRACT FROM AUTHOR]

Objective(s): Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method.Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P

Introduction: Proinflammatory cytokines released from nerve endings and surrounding injured tissue after nerve damage can prolong the inflammation process, delay nerve healing or result in poor quality nerve healing. In this case, due to the loss of function in the muscles innervated by the damaged nerve, the patient may have neurological and functional difficulties which may reduce the patient's quality of life and create an economic burden. Although the attempts of many pharmacological agents to heal crush injury of peripheral nerves have been recorded in literature, a drug that can provide adequate recovery of the crushed nerve and can be applied in daily life has not been defined as yet. This study aimed to assess the effects of calcium dobesilate on sciatic nerve crush injury in a rat model.Methods: A total of 26 male Wistar albino rats were separated into four groups as follows: CONTROL group (healthy subjects, n=6); SHAM group (crush injury was created, n=6); MP group (after created crush injury, methylprednisolone was administered, n=7); and CAD group (after created crush injury, calcium dobesilate was administered, n=7). A crush injury was created, then the electrophysiological findings and sciatic nerve functional index (SFI) were recorded before euthanasia. After the euthanasia of all the rats, samples of the crushed nerve and gastrocnemius muscle were evaluated histopathologically, immunohistochemically, and biochemically.Results: Both pharmacological agents were histopathologically effective in axon regeneration and repair. Calcium dobesilate did not preserve total muscle mass but was seen to prevent atrophy microscopically. Immunohistochemistry and biochemistry results showed that calcium dobesilate and methylprednisolone had anti-inflammatory, anti-oxidant, anti-apoptotic, and anti-autophagic activity in the crushed sciatic nerve. Neither calcium dobesilate nor methylprednisolone improved the nerve conductance level. SFI values obtained on day 30 from the CAD group were numerically closer to the values of the healthy animals but not at a statistically significant level.Conclusion: The study results demonstrated that calcium dobesilate could suppress inflammatory processes and provide histopathological and functional improvements in the injured nerve in rats. Therefore, further clinical studies are recommended to investigate in detail the therapeutic effects of calcium dobesilate on peripheral nerve crush injury. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients. Methods: We searched for available randomized controlled studies on DKD patients' treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes. Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD. Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients. [ABSTRACT FROM AUTHOR]

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d‐galactose (d‐gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d‐gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d‐gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d‐gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d‐gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the effectiveness and safety of different dosages of calcium dobesilate in the management of Chronic Venous Insufficiency (CVI) among patients in CEAP classes C3–C4.A comprehensive multicenter retrospective analysis was conducted, including patients aged 18-70 with CEAP class C3–C4 CVI. Participants were divided into two groups: one receiving 500 mg of calcium dobesilate twice daily and the other 1000 mg twice daily. Patient progress was monitored using the Global Index Score, CIVIC-20 Score, and precise measurements of ankle and calf circumferences over a 12-month period.The higher dosage group (1000 mg twice daily) showed significant improvements in both symptom relief and edema reduction. Ankle circumference reduced notably at 6 months, while calf circumference and overall quality of life, measured by the Global Index Score, showed significant improvement by 12 months compared to the lower dosage group.Higher doses of calcium dobesilate markedly enhance the management of CVI symptoms and reduce edema more effectively than lower doses, particularly in patients with advanced CVI. These findings support the use of higher dosages for optimal treatment, though further research is needed to fully evaluate long-term safety. [ABSTRACT FROM AUTHOR]

AIM: To explore the clinical value of fundus retinal argon laser photocoagulation combined with calcium dobesilate in the treatment of diabetic retinopathy(DR).METHODS:A prospective study from August 2017 to August 2019 was conducted. Totally 182 patients(326 eyes)with DR were divided into two groups. The observation group received fundus retinal argon laser photocoagulation combined with calcium dobesilate, and the control group received fundus retinal argon laser photocoagulation. Flash electroretinography was performed before treatment and after treatment, and changes in a and b waves were recorded. Changes in the best corrected visual acuity(BCVA), retinal neovascularization fluorescein leakage area, central macular thickness(CMT)and retinal microcirculation parameters were detected. The absorption time of retinal edema, bleeding and exudation was recorded, and the incidence of postoperative complications was counted.RESULTS: At 6mo after treatment, a-wave and b-wave amplitudes of the two groups were decreased(P0.05). The BCVA of the two groups was increased, and the macular leakage area and CMT were reduced(P0.05).CONCLUSION: Fundus retinal argon laser photocoagulation combined with calcium dobesilate is superior to retinal photocoagulation alone in the treatment of DR. The former can promote the improvement of visual acuity, reduce fluorescein leakage, and promote the absorption of retinal edema, bleeding and exudation, which is conductive to improving retinal microcirculation and inhibiting neovascularization.

Background: Diabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR. Method: 7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models. Results: 19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred. Conclusion: CPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence. Systematic Review Registration: PROSPERO https://www.crd.york.ac.uk/prospero/ , identifier CRD42021257999. [ABSTRACT FROM AUTHOR]

We attempts to discuss the clinical efficacy and application of calcium dobesilate combined with ranibizumab in patients with macular edema secondary to branch retinal vein occlusion. We randomly selected 100 patients with macular edema secondary to branch retinal vein occlusion who had accepted therapy in our hospital from September 2019 to September 2021 as general data. Then divided them into two groups, one was observation group and the other was control group (n=50). Among them, control group was treated with ranibizumab and observation group was treated with calcium dobesilate combined with ranibizumab. Observation group had better changes of best corrected visual acuity and macular foveal thickness after 1 mo, 3 mo and 6 mo treatment than control group. Observation group had better clinical efficacy than control group. Control group had more serious complications than observation group. Calcium dobesilate combined with ranibizumab has a significant clinical effect on patients with macular edema secondary to branch retinal vein occlusion and can reduce complications in patients. [ABSTRACT FROM AUTHOR]

Objective(s): Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods: Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method. Results: CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P<0.05). However, CaD (100 mg/kg) could significantly improve the histopathological change in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). In addition, CaD (100 mg/kg) attenuated the pro and anti-apoptotic markers in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). Conclusion: CaD (100 mg/kg) has a protective effect against hepatorenal injury induced by CCl4 at least via its anti-apoptotic and anti-oxidant properties. [ABSTRACT FROM AUTHOR]

AIM: To analyze the effect of 532nm laser panretinal photocoagulation(PRP)combined with calcium dobesilate on fundus microcirculation and macular thickness in patients with diabetic retinopathy(DR), so as to provide experimental data for their clinical treatment. METHODS: According to the non-randomized clinical concurrent control study and voluntary principle, 174(239 eyes)DR patients were divided into observation group and control group. Both groups were treated with 532nm laser PRP, and the observation group was additionally treated with calcium dobesilate. BCVA(LogMAR)vision, clinical effect, fundus microcirculation, macular thickness and other clinical indexes were compared between the two groups before and after treatment(at 3mo after PRP). The incidence of complications during treatment was statistically analyzed. RESULTS: After treatment, BCVA in both groups were increased, and it was higher in observation group than control group. The clinical curative effect of observation group was better than that of control group(PPPPPPvs 2.6%)(χ2=0.344, P=0.557). CONCLUSION: Compared with 532nm PRP in treatment of DR, curative effect of 532nm PRP combined with calcium dobesilate is better. The latter can improve fundus microcirculation and macular thickness more significantly, with high safety.

Aim: In this study, the objective was to investigate the protective effect of calcium dobesilate, which has antioxidant and anti-inflammatory properties, on the experimental renal ischemia-reperfusion injury (IRI). Methods: Twenty-four male Wistar-Albino rats were divided into three groups: Sham group (Group 1), ischemia-reperfusion group (Group 2), and treatment group (Group 3). Before the ischemia-reperfusion procedure, rats in Group 3 received calcium dobesilate through gavage (100mg/kg/day) for 10 days. Groups other than the sham group underwent ischemia for 45 minutes and reperfusion for 24 hours. Plasma urea and creatinine levels, erythrocyte superoxide dismutase and glutathione peroxidase enzyme activity levels were measured. In addition, histopathological changes that may be related to ischemia-reperfusion injury in the renal tissue, were investigated.Results: The median glutathione peroxidase and superoxide dismutase enzyme levels were higher in Group 2 compared to Groups 1 and 3. However, the differences were not statistically significant. The creatine levels were statistically lower in Group 3 compared to Group 1 and Group 2. The median urea levels were lower in Group 3 than in Group 1 and Group 2, but the differences were not statistically significant. The histopathological examination showed that parameters such as cellular necrosis, flattened tubular epithelial cells, cytoplasmic vacuolization, tubular lumen obstruction, and chronic inflammation, which are indicators of the ischemia-reperfusion injury, were statistically less common in the treatment group compared to the control group. Conclusion: Our study demonstrated that prophylactic calcium dobesilate had a protective effect on ischemia-reperfusion injury.

Pharmacotherapy plays a key role in the treatment of chronic venous diseases and their complications. This category of patients traditionally uses a variety of phlebotropic drugs, the vast majority of which are of plant origin, introducing specific therapeutic features due to decreased bioavailability and, consequently, the presence of a dose-dependent effect. That is why the modern trend in pharmacotherapy of chronic venous diseases is the use of phlebotropic drugs that have high bioavailability with rapid achievement of therapeutic concentration, as well as demonstrating a polyvalent mechanism of action on the main pathogenetic mechanisms of development and progression of chronic venous diseases. One of such preparations is calcium dobesilate, which is a calcium salt of 2,5-dihydroxybenzenesulfonic acid (C12H10CaO10S2) obtained by chemical synthesis. In terms of pharmacological properties calcium dobesilate belongs to capillary protectors with more pronounced pluripotent effect on venous and lymphatic sections of the microcirculation. To date, calcium dobesilate is the only synthetic phlebotropic drug registered in the Russian Federation.Indications for the prescription of calcium dobesilate are microangiopathies of various genesis, but primarily associated with chronic venous and lymphatic failure.Numerous experimental and clinical studies demonstrate a high clinical efficacy of calcium dobesilate regarding major venospecific symptoms and syndromes, for the elimination of which the drug can be prescribed in a standard daily dose of 1500 mg, both in monotherapy and in combination with other drugs.Calcium dobesilate therapy is usually performed without undesirable reactions, the risk of which is low when using standard recommended daily doses of the preparation 500-1500 mg.

BackgroundDiabetic retinopathy (DR), one of the commonest microvascular complications in diabetic patients, is featured by a series of fundus lesions. Conventional Western medicine therapies for DR are always with modest treatment outcome. This paper is to assess the ocular fundus signs, vision and safety of Chinese patent medicines (CPMs) as an add-on treatment for DR.Method7 electronic databases were searched to determine eligible trials. Randomized controlled trials (RCTs) of non-proliferative diabetic retinopathy (NPDR) in which the intervention group received CPMs combined with calcium dobesilate (CD), and the control group received only CD were included for analysis. Two reviewers extracted the data independently. Results expressing as mean differences (MD) and relative risks (RR) were analyzed with a fixed-effects or random-effects models.Results19 RCTs involved 1568 participants with 1622 eyes met our inclusion criteria. The results suggested that compared with CD alone, CPMs plus CD for NPDR was superior at reducing the microaneurysm volume (MD -3.37; 95% confidence interval [CI], -3.59 to -3.14), microaneurysm counts (MD -2.29; 95%CI -2.97 to -1.61), hemorrhage area (MD -0.79; 95%CI -0.83 to -0.75), and macular thickness (MD -59.72; 95%CI -63.24 to -56.20). Participants in CPMs plus CD group also achieved a better vision. No obvious adverse events occurred.ConclusionCPMs as an add-on therapy for NPDR have additional benefits and be generally safe. This meta‐analysis demonstrated that CPMs combined with CD could improve retinal microaneurysm, hemorrhage, macular thickness, visual acuity, fasting blood glucose (FBG), and glycosylated hemoglobin (HbAlc) compared with CD alone. Further studies are needed to provide more conclusive evidence.Systematic Review RegistrationPROSPERO https://www.crd.york.ac.uk/prospero/, identifier CRD42021257999.

Introduction: Diabetic retinopathy is one of the most common causes of blindness in work-aging adults and develops in one third of diabetic patients. Calcium dobesilate (CaD) treatment have protective effects on blood retinal barrier (BRB) and anti-oxidant as well as anti-inflammatory properties. Objectives: To assess effects of CaD administration on retrobulbar blood flow and choroidal thickness in patients with diabetic retinopathy. Methods: In this quasi-experimental study, diabetic patients with diabetic retinopathy (DR) were recruited from Shahid Motahari and Poostchi ophthalmology clinic affiliated to Shiraz University of Medical Sciences. Patients were treated with CaD, 1 gr per day for seven days. Before and after CaD administration, retrobulbar blood flow and subfoveal choroidal thickness were assessed. Retrobulbar blood flow were evaluated by measuring peak systolic velocity (PSV), end diastolic velocity (EDV) and resistive index (RI) of ophthalmic artery (OA), central retinal artery (CRA) and short ciliary artery (SCA). Results: In this study, 26 DR patients with a mean age of 56.15 ± 8.93 years and mean diabetes mellitus duration of 15.04 ± 7.64 years were enrolled. Subfoveal choroidal thickness was significantly increased from 316.08 ± 61.69 to 327.81 ± 58.03 after CaD treatment (P value < 0.001). PSV of CRA and EDV of all arteries were significantly increased after CaD administration. In addition, RI of all arteries was significantly reduced after CaD treatment (P < 0.001). Conclusion: CaD treatment may improve the ophthalmic blood flow and increase the subfoveal choroidal thickness in DR patients. These results may be suggestive of protective effects of CaD on endothelium function as well as microvascular circulation. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study assessed the protective effect of calcium dobesilate against contrast-induced nephropathy (CIN) after coronary angiography (CAG) or percutaneous coronary intervention (PCI) in patients with diabetes and chronic kidney disease (CKD). METHODS: A total of 130 patients with diabetes and CKD estimated glomerular filtration rate: 30-90 mL/min/1.73m2 were enrolled and included in the analysis. They were divided into experimental (n=65) and control groups (n=65). Patients in the experimental group were administered oral calcium dobesilate (500 mg) three times daily for 2 days before and 3 days after the procedure. The serum creatinine (SCr), cystatin C (Cys C), and neutrophil gelatinase-associated lipocalin (NGAL) levels were measured before and after the procedure. RESULTS: The mean SCr level at 24h after the procedure was found to be significantly lower in the experimental group than in the control group (79.1±19.6 μmol/L vs. 87.0±19.3 μmol/L, p=0.023). However, the Cys C and NGAL levels were not significantly different between the two groups at all measurement time points (all p>0.05). The incidence of CIN defined by the SCr level was significantly lower in the experimental group than in the control group (3 [4.6%] vs. 13 [20.0%], p=0.017). However, the incidence of CIN defined by the Cys C level was not statistically different between the two groups (7 [10.8%] vs. 7 [10.8%], p=1.000). CONCLUSIONS: This study revealed that calcium dobesilate has no preventive effect against CIN in patients with diabetes and CKD.

Aim:Anastomotic leakage in colon anastomosis (CA) increases morbidity and mortality. Calcium dobesilate (CaD) has angioprotective, antioxidant, lymphatic flow enhancing-and neuroprotective effects. Despite these capillary and cellular effects, there is no data in the literature regarding the effects of CaD on CA healing.Method:Fifty Wistar-albino rats were randomly divided into five groups. All rats underwent CA after transverse colon transection. CaD was not administered to the control group (Group 1). CaD was administered to the experimental groups (Groups 2, 3, 4 and 5) intraperitoneally or by gavage at doses of 50 or 100 mg/kg/day. CaD was given as a single dose daily during postoperative five days. Bursting pressure values (BPV) and hydroxyproline values (HV) were measured. At the end of istopathological evaluation, polymorphonuclear leukocytes (PNLS), mononuclear leukocytes (MNLS), neovascularization (VS) and collagen fibers (CFS) were scored.Results:CaD increased BPV and HV in experimental groups. We found a decrease in PNLS, MNLS, VS, and an increase in CFS in experimental groups. These increases seemed to be related to the administration doses of CaD. The decreases in PNLS, MNLS and VS were much more evident in Groups 4 and 5 than the other groups. There was no significant difference in terms of VS between experimental groups.Conclusion:We found that CaD not only decreased the pathological parameters of inflammation, but also increased the strength of CA mechanically and biochemically. Although VS reduction seemed to have negative outcomes on CA, we know that CaD inhibits over-expression in angiogenesis. As a result, these effects of CaD appear to be dose-dependent rather than the administration methods.

AIM: To investigate the clinical value of epalrestat combined with compound anisodine in treatment of non-proliferative diabetic retinopathy(NPDR).METHODS: According to the random remainder method, they were divided into A, B and C three groups. Group A was treated with calcium dobesilate, group B was treated with epalrestat, and group C was treated with epalrestat combined with compound anisodine. All groups were treated for 6mo. The BCVA and fundus color photos, fundus fluorescein angiography(FFA), oscillatory potentials of electroretinogram(ERG-Ops)and optical coherence tomography(OCT)were performed before and after 1mo, 3mo and 6mo of treatment. The therapeutic effect was evaluated. RESULTS: Before treatment, there was no statistical difference among the three groups in BCVA, Ops wave amplitude or central macular thickness(P>0.05). The BCVA was improved, Ops wave amplitude was increased and the central macular thickness was decreased in the three groups after 1mo, 3mo and 6mo of treatment. Compared with the same group before treatment, there were statistically significant differences(PPPPCONCLUSION: Epalrestat combined with compound anisodine is effective in treatment of DR. The combined treatment can significantly improve the visual acuity, relieve macular edema and promote the recovery of retinal function.

Purpose/Aim of the study: Inflammation and oxidative stress are two significant factors affecting the degree of liver damage in obstructive jaundice. The aim of this study was to evaluate the effect of calcium dobesilate (CaDob), an effective antioxidant and anti-inflammatory drug, on damage to liver caused by experimental obstructive jaundice. Materials and Methods: 30 rats in total were randomly placed into three groups, each group consisting of 10 rats. The sham group (Group 1) only received solely laparotomy. In the control group (Group 2), ligation was applied to the biliary tract and no treatment was implemented. In the CaDob group (Group 3), following ligation of the biliary tract, 100 mg/kg/day CaDob was implemented via an orogastric tube for a 10–day period. Liver tissue and blood samples were taken for histopathological and biochemical examination. Results: The CaDob group had significantly lower test values for serum liver functions when compared to the control group. Statistically lower levels of tissue malondialdehyde (MDA) and fluorescent oxidation products (FOP) were detected in the CaDob group, and the CaDob group had significantly higher levels of sulfydryl (SH) than the control group. Histopathological scores in the CaDob group were found out to be statistically less than the scores the control group received (p < 0.05). Conclusions: CaDob treatment repaired the histpatological changes induced by bile duct ligation. The hepatoprotective effects of CaDob can be associated with its antioxidant properties of the drug.