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<b>Introduction:</b> Hemorrhoidal disease is the most common disease treated in proctology ambulatories. Conservative treatment is the basic form of treatment for this disease. One of the elements of treatment may be preparations with myoand phlebotropic effects.<b>Aim:</b> To assess the effect of a multi-ingredient myophlebotropic dietary supplement used as an adjunct on the rate and effectiveness of symptom relief in patients with stage II and III hemorrhoidal disease.<b>Material and method:</b> Patients with stage II and III hemorrhoidal disease with clinical symptoms such as pain, burning, itching and bleeding were qualified for the study. The patients were divided into two groups. The control group (Group I) of 29 patients receiving standard local treatment plus placebo and the study group (Group II) of 32 patients receiving the same local treatment and a six-component myophlebotropic product. Symptoms were analyzed at the time of inclusion in the study (day 0), after 4 and 10 days of therapy. The severity of hemorrhoidal disease and the feeling of relief were assessed on the day of inclusion (W0) and after 30 days of therapy.<b>Results:</b> There were no statistical differences between the groups in terms of disease advancement, age, gender, and duration of symptoms. Compared to the moment of inclusion in the study (W0), after 4 days (W1), after 10 days (W2) of taking the multi- -component product, there was a statistically significant improvement in the VAS scale: spontaneous pain and pain during defecation. In the qualitative assessment (yes/no), there were statistically significantly fewer cases of burning in the anus and itching. The treatment did not affect the rate of spontaneous bleeding, which was low at the beginning of the study, but significantly reduced the rate of bleeding during defecation. After 30 days of observation, it was found that the improvement in the severity of hemorrhoidal disease symptoms was significantly higher in the group using the tested preparation. Relief after a month of the study (one-question method) was noted in the group of patients receiving the tested product.<b>Conclusions:</b> The tested six-component myophlebotropic product proved to be effective in reducing the severity of symptoms such as spontaneous pain, pain during defecation, burning/burning in the anus and bleeding during defecation. Statistical significance was demonstrated in the symptom\'s relief and reduction in the severity of hemorrhoidal disease.

BACKGROUND: Pelvic congestion syndrome (PCS) is associated with chronic pelvic pain (CPP). The efficacy of flavonoids for treating PCS symptoms is still a matter of debate, and little has been published. The aim of this study was to assess the efficacy of a mixture of diosmin, troxerutin, and hesperidin in improving symptoms of patients with PCS, observing a direct effect on circulation by specific color Doppler ultrasonography (CDU) evaluations.
METHODS: This was a pilot, prospective, independent, cross-over, daily-diary-based trial. Women were evaluated with CDU for 3 times (baseline, 60 days, 120 days). Data about N.=13 women who completed the study were analyzed.
RESULTS: During the treatment, we recorded a significant reduction of intermenstrual and menstrual pain intensity (total points) (P<0.05). The satisfaction after treatment was significantly higher than after placebo (P<0.0001). A significant reduction in the diameter of the major ovarian vein (P=0.004 compared to placebo), associated with an increase in peak systolic velocity (P=0.01) and a corresponding significant increase in the Resistivity Index (P<0.0001) were recorded during treatment.
CONCLUSIONS: The use of a mixture of diosmin, troxerutin and hesperidin in women with PCS can significantly help to manage typical symptoms of pelvic pain and it is associated with an evident Doppler effect on pelvic microcirculation.

Reproductive deficiency is a major outcome of pesticide exposure sequel to cellular oxidative damage to sex organs. Flavonoid possess potent antioxidant capacities to mitigate pesticide related cellular injury. The present investigation examined the mitigative effect of micronized purified fractions of diosmin and hesperidin on reproductive hormones, sperm parameters, and testicular glycogen in male Wistar rats after sub-chronic Chlorpyriphos (CPF) exposure. Twenty-five male Wistar rats (120-145 g) were randomly allocated five rats per group. Group I (DW) received distilled water (2 ml/kg), Group II (S/oil) received soya oil (2 ml/kg), Group III (DAF) received Daflon at 1000 mg/kg, Group IV (CPF) received Chlorpyriphos (7.74 mg/kg), and Group V (DAF + CPF) received Daflon (1000 mg/kg) followed by CPF (7.74 mg/kg) after 30 min of Daflon. This regimen was administered daily for 60 days. After cervical venesection under light chloroform anesthesia, blood samples were examined for levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Each rat\'s testicular tissue was quickly cut, collected, and glycogen evaluated. Sperm concentration, motility, morphology, and viability were measured in the right caudal epididymis. Results revealed that the untreated CPF group had significantly lower FSH, LH, testosterone, testicular glycogen, and sperm concentration. Additionally, CPF group sperm characteristics were abnormal compared to other groups. These reproductive hormones, testicular glycogen, and sperm parameters improved in the Daflon-treated groups. Hence, pre-treatment with flavonoid fractions of diosmin and hesperidin mitigated CPF-induced reproductive toxicity.

Chemotherapeutic drugs, such as doxorubicin (Dox), are commonly used to treat a variety of malignancies. However, Dox-induced cardiotoxicity limits the drug\'s clinical applications. Hence, this study intended to investigate whether diosmin could prevent or limit Dox-induced cardiotoxicity in an animal setting. Thirty-two rats were separated into four distinct groups of controls, those treated with Dox (20 mg/kg, intraperitoneal, i.p.), those treated with diosmin 100 mg plus Dox, and those treated with diosmin 200 mg plus Dox. At the end of the experiment, rats were anesthetized and sacrificed and their blood and hearts were collected. Cardiac toxicity markers were analyzed in the blood, and the heart tissue was analyzed by the biochemical assays MDA, GSH, and CAT, western blot analysis (NF-kB, IL-6, TLR-4, TNF-α, iNOS, and COX-2), and gene expression analysis (β-MHC, BNP). Formalin-fixed tissue was used for histopathological studies. We demonstrated that a Dox insult resulted in increased oxidative stress, inflammation, and hypertrophy as shown by increased MDA levels and reduced GSH content and CAT activity. Furthermore, Dox treatment induced cardiac hypertrophy and damage, as evidenced by the biochemical analysis, ELISA, western blot analysis, and gene expression analysis. However, co-administration of diosmin at both doses, 100 mg and 200 mg, mitigated these alterations. Data derived from the current research revealed that the cardioprotective effect of diosmin was likely due to its ability to mitigate oxidative stress and inflammation. However, further study is required to investigate the protective effects of diosmin against Dox-induced cardiotoxicity.

Neurological injury is a crucial problem that interferes with the therapeutic use of vinca alkaloids as well as the quality of patient life. This study was conducted to assess the impact of using loratadine or diosmin/hesperidin on neuropathy induced by vinca alkaloids. Patients were randomized into one of three groups as follows: group 1 was the control group, group 2 received 450 mg diosmin and 50 mg hesperidin combination orally twice daily, and group 3 received loratadine 10 mg orally once daily. Subjective scores (numeric pain rating scale, douleur neuropathique 4, and functional assessment of cancer therapy/gynecologic oncology group-neurotoxicity (FACT/GOG-Ntx) scores), neuroinflammation biomarkers, adverse drug effects, quality of life, and response to chemotherapy were compared among the three groups. Both diosmin/hesperidin and loratadine improved the results of the neurotoxicity subscale in the FACT/GOG-Ntx score (p < 0.001, p < 0.01 respectively) and ameliorated the upsurge in neuroinflammation serum biomarkers. They also reduced the incidence and timing of paresthesia (p = 0.001 and p < 0.001, respectively) and dysuria occurrence (p = 0.042). Both loratadine and diosmin/hesperidin attenuated the intensity of acute neuropathy triggered by vinca alkaloids. Furthermore, they did not increase the frequency of adverse effects or interfere with the treatment response.

BACKGROUND: Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats.
METHODS: In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated.
RESULTS: DOX-induced reduce spermatogenic function, testicular 3- and 17β-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis.
CONCLUSIONS: It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX\'s harmful effects.

Doxorubicin (DOX) can be applied to treat several cancers. DOX-induced oxidative stress causes testicular damage. Diosmin (DIO), as a potent antioxidant, reduces many drugs\' side effects. We determined DIO therapeutic effects on DOX-related testicular toxicity. Forty rats were assigned to five groups as control, DOX (2.5 mg/kg six i.p. injections at equal intervals over two weeks), DOX + DIO (25, 50, 100 mg/kg, orally, daily, for two weeks) groups. Oxidative and antioxidant markers, fertility parameters levels, sperm parameters, and a histopathological examination were analyzed. DOX group showed a significant decrease in the number of spermatogonia, primary spermatocytes, and sertoli cells, seminiferous tubular diameter, seminiferous luminal diameter, and seminiferous epithelial height. Moreover, testosterone levels, glutathione (GSH) levels, catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD) activities showed a significant decrease. Furthermore, nitric oxide (NO) and malondialdehyde (MDA) contents and also follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels showed a significant increase in the DOX group compared to the control group. DIO improved DOX-related alterations in levels of hormones, spermatogonia, spermatocytes, and sertoli cell number, and seminiferous diameters (tubular, luminal, and epithelial height). Furthermore, GSH level, SOD, GPx, and CAT activities showed a significant increase, and MDA and NO contents showed a significant decrease in the DOX + DIO group than the DOX group. The results indicate that DIO mitigate DOX-induced testicular toxicity by its anti-oxidant activity.

Doxorubicin (DOX) is the cornerstone of chemotherapy. However, it has dose-dependent cardiotoxic events that limit its clinical use. This study was intended to investigate the efficiency of DOX as an anti-cancer against the MCF-7 cell line in the presence of diosmin (DIO) and to appraise the protective impact of DIO against DOX cardiotoxicity in vivo. In vitro study was carried out to establish the conservation of DOX cytotoxicity in the presence of DIO. In vivo study was conducted on 42 adult female Wistar rats that were equally allocated into 6 groups; control, DIO (100 mg/kg), DIO (200 mg/kg), DOX (20 mg/kg, single dose i.p.), DIO (100 mg/kg) + DOX, received DIO orally (100 mg/kg) for 30 days, then administrated with a single dose of DOX and DIO (200 mg/kg) + DOX, received DIO orally (200 mg/kg) for 30 days, then administrated with DOX. In vitro study showed preservation of cytotoxic activity of DOX on MCF-7 in the presence of DIO. In vivo study indicated that DOX altered electrocardiograph (ECG) parameters. Also, it yielded a significant rise in CK-MB, cTnT and LDH serum levels and cardiac contents of MDA, IL-1β; paralleled by a significant drop in cardiac IL-10 and SOD. Moreover, significant upregulation of Bax, TNF-α, and HIF-1α, in concomitant with significant downregulation of Bcl-2 mRNA in cardiac tissue have been recorded in the DOX group. Furthermore, histopathological description of cardiac tissues showed that DOX alters normal cardiac histoarchitecture. On the opposite side, DIO pretreatment could ameliorate ECG parameters, suppress IL-1β and enhanceIL-10, promote activity of SOD and repress MDA. Additionally, downregulation of Bax, TNF-α, HIF-1α and upregulation of Bcl-2 have been demonstrated in DIO-pretreated rats. Furthermore, the histopathological examination of cardiac tissues illustrated that DIO had a favorable impact on the protection of heart histoarchitecture. DIO is suggested for protection against acute cardiotoxicity caused by DOX without affecting antitumor activity.

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