Oral Silymarin Research Articles

Silymarin in combination with hair follicle transplantation as a potential treatment for refractory vitiligo: A double-blind randomized controlled trial.

There is still no certain effective treatment for vitiligo as a common chronic skin disorder characterized by depigmented patches and loss of skin melanocytes. This study evaluates the efficacy of oral silymarin combined with hair follicle transplantation compared to follicle transplantation alone in the treatment of refractory vitiligo. Twenty refractory vitiligo patients were enrolled in this randomized controlled clinical trial, following up for 3 months. One group underwent hair transplantation plus oral silymarin, while the other group underwent follicle transplantation alone. We assessed the progress with Vitiligo Extent Tensity Index (VETI) in both groups and the peri-follicular pigmentation diameter was estimated monthly. The Friedman test for comparing two groups at the end and the Mann-Whitney test for comparing two groups during each month was used. The mean age was 30.22 (18-59) years, with the male to female ratio of 1:1. The decrease in the VETI and increase in the perifollicular pigmentation was statistically significant between silymarin and another group in monthly follow-up (p-value: 0.019, 0.019, and 0.035, respectively). Finally, the re-pigmentation was notable in silymarin group (p-value <0.001 vs. 0.029, respectively). In addition, both genders had a significant increase in peri-follicular re-pigmentation in the last follow-up (p-value: 0.012 and 0.044, respectively); although the improvement was not statistically significant between genders in each month. According to our study, silymarin in combination with hair transplantation could be a potential medical treatment for vitiligo; however, further trials are needed to establish the efficacy of combination therapies.

Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.

Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from Silybum marianum, may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients. In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140 mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study. Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group. Oral formulation of silymarin 420 mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.

In Vivo Antioxidant and Nephroprotective Effects of Ethanolic Extract of Carica papaya Seeds and Its Isolated Flavonoid on Gentamicin-Induced Nephrotoxicity in Wistar Albino Rats.

Background The nephrotoxic side effects of gentamicin, a potent aminoglycoside antibiotic, significantly restrict its clinical use. Identifying compounds that can mitigate this nephrotoxicity is of paramount importance. The research examines how the ethanolic extract of Carica papaya seeds (EECPS) and isoliquiritigenin (ISL), a flavonoid separated from them, protect the kidneys and fight free radicals in gentamicin-treated Wistar albino rats. Methodology A total of 48 mature Wistar albino rats were divided into eight groups, with each group consisting of six rats. The experimental setup included a normal control group receiving oral saline as a negative control, and a standard control group administered gentamicin intraperitoneally (IP) at 100 mg/kg body weight for 13 days to induce nephrotoxicity, followed by oral silymarin at 100 mg/kg body weight as a positive control from days 14 to 21. A toxicant control group was exposed to gentamicin IP without subsequent treatment. Two test groups were given 400 mg/kg and 800 mg/kg of EECPS orally after being given gentamicin. Three other test groups were given 20 mg/kg, 40 mg/kg, and 80 mg/kg of ISL orally after being given gentamicin. Serum levels of creatinine, urea, and blood urea nitrogen (BUN) were used to test renal function. Malondialdehyde (MDA),nitric oxide (NO), and reduced glutathione (GSH), which are signs of oxidative stress, were also measured in renal tissues. Results Gentamicin administration markedly increased serum creatinine, urea, and BUN levels, confirming its nephrotoxic effect. Nephroprotection depended on the dose of EECPS and ISL used. It was found that 80 mg/kg of ISL had the most powerful effect, which was not what was thought at first. These treatments effectively reduced MDA and NO levels while enhancing GSH levels, exhibiting their strong antioxidant properties. Notably, the nephroprotective efficacy of these treatments exceeded that of silymarin, a known nephroprotective agent. Histopathological analysis confirmed reduced renal damage and enhanced tissue repair in the treated groups. Conclusions These findings demonstrate how effective EECPS and ISL are at shielding the kidneys from gentamicin-caused damage. They do this by acting as antioxidants and nephroprotectants. Their ability to protect kidney function and fight oxidative stress makes them interesting as possible treatments for gentamicin-related kidney damage. These results advocate for further investigation into the utility of these natural compounds in the management of nephrotoxicity.

Effect of oral silymarin on liver function in pediatric acute lymphoblastic leukemia in the maintenance phase: a double-blind randomized clinical trial.

Introduction: Liver dysfunction is one of the most common disorders in patients with acute lymphoblastic leukemia (ALL). In recent studies, silymarin has been observed to have hepatic protective effects. Therefore, in this study, the effect of oral silymarin on the hepatic functions of patients with ALL was investigated. Methods: In the present double-blind clinical trial study, 121 patients with ALL over 5years of age were divided into two groups after obtaining informed consent. The subjects were randomly divided into a silymarin-treatment group and a placebo group. In the silymarin-treatment group, patients received 70mg oral capsules of silymarin twice daily or syrup of silymarin three times a day (each 5ml of syrup contains 50mg of silymarin). Patients were examined once a month for 9months to receive capsules and measure the levels of alanine aminotransferase (ALT), aspartate transferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, albumin, and cholesterol. Results: Comparison of changes before and after treatment in the two groups showed that receiving oral silymarin resulted in a slight significant decrease in the levels of ALT, AST, GGT, and bilirubin (p < 0.05), but had no effect on ALP, albumin, and cholesterol (p > 0.05). Discussion: The results of the present study showed that in pediatric patients with ALL, silymarin intake improves liver function. The very strong antioxidant effect of silymarin may explain its protective effect on the liver. Clinical Trial Registration: IRCT20150119020715N10.

The Effect of Oral Silymarin on Remdesivir-Induced Hepatotoxicity and Clinical Course in Covid-19 Patients; A Double-Blind Randomized Controlled Trial

The Effect of Oral Silymarin on Remdesivir-Induced Hepatotoxicity and Clinical Course in Covid-19 Patients; A Double-Blind Randomized Controlled Trial

Silymarin Encapsulated Liposomal Formulation: An Effective Treatment Modality against Copper Toxicity Associated Liver Dysfunction and Neurobehavioral Abnormalities in Wistar Rats.

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly (p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period (p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: a comprehensive review of preclinical and clinical data.

Thus far, silymarin has been examined in several studies for prevention or treatment of various chemotherapy or radiotherapy-induced adverse reactions. In this review, we try to collect all available human, animal, and pre-clinical data in this field. The search was done in Scopus, PubMed, Medline, and systematic reviews in the Cochrane database, using the following keywords: "Cancer," "Chemotherapy," "Radiotherapy," "Mucositis," "Nephrotoxicity," "Dermatitis," "Ototoxicity," "Cardiotoxicity," "Nephrotoxicity," "Hepatotoxicity," "Reproductive system," "Silybum marianum," "Milk thistle," and "Silymarin" and "Silybin." We included all relevant in vitro, in vivo, and human studies up to the date of publication. Based on 64 included studies in this review, silymarin is considered a safe and well-tolerated compound, with no known clinical drug interaction. Notably, multiple adverse reactions of chemotherapeutic agents are effectively managed by its antioxidant, anti-apoptotic, anti-inflammatory, and anti-immunomodulatory properties. Clinical trials suggest that oral silymarin may be a promising adjuvant with cancer treatments, particularly against hepatotoxicity (n = 10), nephrotoxicity (n = 3), diarrhea (n = 1), and mucositis (n = 3), whereas its topical formulation can be particularly effective against radiodermatitis (n = 2) and hand-foot syndrome (HFS) (n = 1). Further studies are required to determine the optimal dose, duration, and the best formulation of silymarin to prevent and/or manage chemotherapy and radiotherapy-induced complications.

Experimental Design and Optimization of Nano-Transfersomal Gel to Enhance the Hypoglycemic Activity of Silymarin.

Current advancements in the research investigations focused at using natural products to generate novel dosage forms with a potential therapeutic impact. Silymarin is a natural product obtained from the herb Silybum marianum that has been shown to have remarkable hypoglycemic activity. Owing to the low enteral absorption, instability in stomach secretion, and poor solubility of Silymarin, it was better to be produced as a topical dosage form. A three-factor, three-level Box Behnken (33 BB) design was constructed to develop 15 formulations using three independent variables (phospholipid concentration, surfactant concentration, and sonication time) and two dependent variables (encapsulation efficiency and in vitro drug release). The optimized formula was added to HPMC gel and the resulting transfersomal gel was investigated for its characteristics, in vitro, ex vivo and hypoglycemic behaviors. The pH of the Silymarin-loaded transfersomal gel was 7.05, the spreadability was 55.35 mm, and the viscosity was 6.27 Pa. Furthermore, Silymarin loaded transfersomal gel had the greatest transdermal flux (92.41 µg/cm2·h), which was much greater than all other formulations. In vivo observations revealed that Silymarin loaded transfersomal gel significantly reduced blood glucose levels, compared to either Silymarin gel or oral Silymarin suspension. The findings show that the developed transfersomal gel could be an effective carrier for Silymarin transdermal delivery.

Characterisation of Preformulation Parameters to Design, Develop and Formulate Silymarin loaded PLGA Nanoparticles for Liver Targeted Drug Delivery

Silymarin, a flavonolignan,derived from Silybum marianum, family Asteraceae has long been used as a hepatoprotective remedy. Silymarin has cytoprotective activities due to its antioxidant property and free radical scavenging activity. It inhibits the binding of hepatotoxins to receptor sites, protects hepatocyte membranes, enhances liver parenchyma regeneration and increases glutathione levels. The pharmacokinetic studies of past three decades revealed that Silymarin has poor absorption, rapid metabolism especially by Phase II metabolism and ultimately poor oral bioavailability. Typical oral adult dose of Silymarin is 240-800mg /day .It is a non-lipophilic and poorly water soluble compound with water solubility of 0.04mg/ml. Only 20-30% of oral Silymarin is absorbed from gastrointestinal tract where it undergoes extensive entero-hepatic circulation. The advanced type of formulation like polymeric nanoparticles (PNPs) can be successfully utilised for bioavailability enhancement and targeting the Silymarin to hepatocytes. A controlled release PNP of Silymarin was prepared by solvent evaporation method using Poly Lactic-co-Glycolic Acid (PLGA) as biodegradable polymer. Prior to the development of this novel dosage form, it is very important to identify fundamental physical and chemical properties of the drug molecule and other divided properties of the drug powder. This data helps in many of the subsequent events and approaches towards the development of a better formulation. Preformulation studies included determination of solubility, moisture content, partition coefficient, melting point , powder properties like tapped density, bulk density, compressibility index, flow properties like angle of repose, excipient compatibility, entrapment efficiency, release profile of nanoparticles like dissolution, stability studies like effect of temperature and humidity and analysis by scanning Electron Microscopy.

In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide.

Morinda elliptica L. (Rubiaceae) is a phytomedicinal herb, used to treat gastrointestinal complications in Peninsular Malaysia. The study evaluates the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats. Thirty adult rats were divided into five groups of six rats each. Rats of the normal control group received intraperitoneal injections (i. p.) of vehicle 10% Tween-20, 5ml/kg, and hepatotoxic group 200 mg/kg TAA three times per week respectively. Three supplementary groups were treated with TAA plus daily oral silymarin (50 mg/kg) or M. elliptica (250 or 500 mg/kg). After 8 weeks of treatment, all rats were sacrificed. Liver fibrosis was assessed by gross macroscopic and microscopic tissue analysis, histopathological, and biochemical analysis. The livers of the TAA treated group showed uniform coarse granules, hepatocytic necrosis with lymphocytes infiltration. Contrary, the livers of M. elliptica treated groups (250 and 500 mg/kg) were much smoother and the cell damage was much lesser. The livers of M. elliptica treated groups rats showed elevated activity of SOD and CAT with a significant decrease in MDA level at p < .0001. The level of liver damage parameters, that is, ALP, ALT, and AST, bilirubin, total protein, and albumin were restored to the normal comparable to silymarin. M. elliptica stem extract significantly promoted normal rat liver architecture with significant perfections in biochemical parameters. The molecular contents of M. elliptica with hepatoprotective influence could be discovered, is the future prospective of this study.

A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice

ObjectiveTo evaluate the synergic effects of a novel oral supplement formulation, containing prebiotics, yeast β-glucans, minerals and silymarin (Silybum marianum), on lipid and glycidic metabolism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced obese mice. MethodsAfter an acclimation period, 32 male C57BL/6 mice were divided into the following groups: nonfat diet (NFD) vehicle, NFD supplemented, high-fat diet (HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally by gavage once a day during the last four weeks of the diet (28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of mice. ResultsAfter four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia, fat, and hepatic fibrosis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator-1α, and mitochondrial transcription factor A expression levels were augmented; however, levels of inhibitor of nuclear factor-κB kinase subunit α and p65 nuclear factor-κB expression, and oxidative markers were reduced. Notably, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic–pituitary–adrenal axis immune interface status, was found to be modulated by the supplement. ConclusionWe discovered that the novel supplement was able to modify different antioxidant, metabolic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

Oral silymarin formulation efficacy in management of AC-T protocol induced hepatotoxicity in breast cancer patients: A randomized, triple blind, placebo-controlled clinical trial

Chemotherapeutic agents, with or without other drugs and radiation, may cause indirect or direct hepatotoxicity. Doxorubicin-induced hepatotoxicity (DIH) is a major health concern in cancer patients receiving this cytotoxic drug that is mostly resulted from the production of reactive oxygen species leading to transient or permanent liver damages. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. This study aimed to investigate the clinical efficacy of systemic administration of silymarin in management of chemotherapy induced hepatotoxicity in patients with non-metastatic breast cancer who received doxorubicin/cyclophosphamide-paclitaxel (AC-T) regimen.Material: In this randomized, triple blind, placebo-controlled clinical trial, 30 patients who received AC-T who fulfilled the inclusion criteria were randomly allocated to silymarin (n = 15) or placebo (n = 15) groups to receive oral silymarin 140 mg three times a day or placebo tablets, respectively. Fatty liver severity was assessed by liver ultrasound imaging and FibroScan® and also measurement of liver function tests before and after the intervention. There was a non-significant trend toward more severe liver involvement in placebo group comparing to the silymarin group after intervention based on ultrasonography (p = 0.083). Besides, in silymarin group, hepatic involvement grade based on ultrasonography considerably reduced after intervention (p = 0.012). However, no difference was found between two groups based on FibroScan and liver function tests. Oral administration of silymarin could significantly reduce hepatotoxicity severity after 1 month of treatment in non-metastatic breast cancer patients treated with AC-T regimen.

Silymarin effect on experimental bone defect repair in rat following implantation of the electrospun PLA/carbon nanotubes scaffold associated with Wharton's jelly mesenchymal stem cells.

In this study, the ability of silymarin to heal rat calvarial bone critical defects with mesenchymal stem cells isolated from human Wharton's jelly (HWJMSC) cultured on the electrospun scaffold of poly (lactic acid)/carbon nanotube (PLA/CNT) has been examined. In this study, 20 adult male Wistar rats were divided into four groups of five each. Under general anesthesia, 8 mm defects were created in the calvarial bone of the rats. Then, study groups were defined as no treatment group, the scaffold alone, the scaffold and HWJMSCs, and the scaffold/cells plus oral silymarin, respectively. The histomorphometric study was performed using H&E staining and Goldner's Masson trichrome as specific staining. The results of this study showed that the electrospun PLA/CNT scaffold is a biocompatible scaffold and HWJMSCs can considerably attach and proliferate on this scaffold, and the scaffold itself is also a suitable option for improving the bone repair process. The results of the histomorphometric analysis also showed a significantly higher amount of recently formed bone in the silymarin group plus scaffold/cells compared to the scaffold and cell group alone (p < .05). Utilizing silymarin plus HWJMSCs cultured on PLA/CNT scaffold can be used as a suitable method for the process of osteogenesis and bone repair.

Can we consider silymarin as a treatment option for vitiligo? A double-blind controlled randomized clinical trial of phototherapy plus oral Silybum marianum product versus phototherapy alone

Introduction: Vitiligo is a chronic skin disorder caused by destruction of the skin melanocytes, which presents as a depigmented area in the skin. This study examined the effect of Phototherapy plus oral Silybummarianum on the treatment of skin lesions of Vitiligo.Materials and methods: In this randomized controlled clinical trial, 34 patients with vitiligo who were referred to Dermatology Clinic of Shahid Faghihi Hospital, Shiraz, Iran, were randomly divided into two groups. The first group was treated with phototherapy plus Narrowband UVB plus oral silymarin and the other group was treated with phototherapy with placebo. The patients in both groups were evaluated with vitiligo area severity index (VASI) at the beginning and end of the study. SPSS software version 23 was used for statistical analyses.Results: The mean of the VASI score showed a statistically significant decrease in both groups at the end of the study (p < .05), but the decrease in the VASI score in patients who received Silybum marianum was more in comparison with the other group.Conclusion: This study showed that probably Silybum marianum is a good choice for patients with vitiligo; however, further studies are recommended to be conducted to confirm our result.

Differential Effects of Silymarin on Pitavastatin Disposition in Rodent Models of Simple Fatty Liver versus Nonalcoholic Steatohepatitis: A Natural Product‐Disease‐Drug Interaction

Nonalcoholic fatty liver disease (NAFLD) progresses from simple fatty liver (SFL) to nonalcoholic steatohepatitis (NASH). This progression alters hepatic organic anion transporting polypeptide (OATP/Oatp) uptake transporters and the pharmacokinetics of some xenobiotics after intravenous administration. Comparatively less is known about how diet‐induced NAFLD alters xenobiotic pharmacokinetics after oral administration. Investigation of NAFLD pharmacotherapy options has included the natural product silymarin. How silymarin‐mediated inhibition of transporters interacts with NASH‐associated changes in transporters is not known. The objective of this study was to assess the interaction between silymarin and the OATP/Oatp substrate pitavastatin in the context of SFL and NASH. Male Sprague Dawley rats were fed different diets to model stages of NAFLD: control (healthy), fructose‐palmitic acid‐cholesterol (SFL), or methionine and choline deficient (NASH). Pitavastatin (2.5 mg/kg) was administered via oral gavage, silymarin (500 mg/kg) or vehicle was administered 40 minutes later via oral gavage, and plasma was collected serially from the tail vein to 27 hours. Silymarin flavonolignans and pitavastatin were measured by LC‐MS/MS, and the pharmacokinetics were determined using noncompartmental methods. Trend analysis indicated that Cmax values for the silymarin flavonolignans and corresponding glucuronides increased from healthy to SFL to NASH. These data are the first to show that SFL alters a pharmacokinetic endpoint and suggest that certain intestinal and/or hepatic mediators change incrementally during NAFLD progression. Indeed, a decreasing trend in hepatic Oatp1b2 protein expression was observed from healthy to SFL to NASH. NASH alone increased pitavastatin AUC0‐27h 3.0‐fold compared to the healthy vehicle‐treated group. Silymarin increased pitavastatin AUC0‐27h in both the healthy and NASH groups by a similar extent (~1.7‐fold increase compared to the respective vehicle‐treated groups for each diet). The combination of NASH and silymarin had the greatest effect on pitavastatin AUC0‐27h (4.9‐fold increase compared to the healthy vehicle‐treated group). SFL had no effect on pitavastatin disposition but, unexpectedly, the silymarin effect on pitavastatin AUC0‐27h was diminished in the SFL group (1.3‐fold increase compared to a 1.6‐ and 1.8‐fold increase in the healthy and NASH groups, respectively). The multiple peaks in plasma concentrations of all silymarin flavonolignans after 4 hours were largely abolished in the SFL and NASH groups. These data may implicate changes in microbiome‐mediated glucuronidase activity, enterohepatic cycling, and/or intestinal absorption processes. Collectively, patients with NASH may be at increased risk for adverse silymarin‐drug interactions involving pitavastatin and potentially other OATP substrates.Support or Funding InformationThis work was supported by the National Institutes of Health grants 4R00ES024455 and U54AT008909 and the Washington State University College of Pharmacy and Pharmaceutical Sciences.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Effects of silymarin on angiogenesis and oxidative stress in streptozotocin-induced diabetes in mice.

The present study evaluated the effects of acute treatment with silymarin, an extract that is obtained from Silybum marianum, on angiogenesis, oxidative stress, and inflammation in normoglycemic and diabetic mice. Diabetes was induced by streptozotocin (80 mg/kg, intraperitoneal) in male Swiss mice, 6 weeks of age. A polyether-polyurethane sponge was surgically implanted in the back of the mice as a model of healing in both diabetic and normoglycemic animals that were treated with oral silymarin or water for 10 days. The pancreas, liver, kidneys, blood, and sponges were collected and analyzed. Diabetes led to impairments of antioxidant defenses, reflected by a reduction of pancreatic superoxide dismutase and hepatic and renal catalase and an increase in pancreatic lipoperoxidation. An inflammatory process was observed in diabetic mice, reflected by an increase in pancreatic tumor necrosis factor α (TNF-α) and the infiltration of inflammatory cells in islets. The number of vessels was lower in the implanted sponges in diabetic mice. Silymarin treatment attenuated this damage, restoring antioxidant enzymes and reducing pancreatic TNF-α and inflammatory infiltration. However, silymarin treatment did not restore angiogenesis or glycemia. In conclusion, treatment with silymarin red uced oxidative stress and inflammation that were induced in the model of streptozotocin-induced diabetes in several organs, without apparent toxicity. Silymarin may be a promising drug for controlling diabetic complications.

Adjuvant effect of oral Silymarin on patients' wound healing process caused by thermal injuries.

Background:According to the side effects of the usual treatment of burns, in improving the patients’ prognosis, there is a need to introduce faster and more effective adjuvant therapies to treat wounds, thus to improve the prognosis of patients. The aim of this study was to investigate the effect of adjuvant treatment with oral silymarin on wound healing process caused by second degree-burns among the patients admitted to Valiasr Hospital of Arak.Methods: This randomized, double-blind clinical trial study was carried out on 80 patients with second-degree burns covering 20 to 30 percent of the body with flame. Patients were randomized into 2 groups with an equal number: The intervention group (treated daily with oral 140-mg silymarin) and control (under the administration of placebo). Patients were treated for 8 weeks and at the end of weeks 1, 2, 3 and 4 according to the degree of wound healing (grade 1, 2 and 3) were followed during 2016-2017. Results:Changes in degrees of burn wound healing in both the intervention and placebo groups during the 4 weeks of treatment, significantly improved grade 3 completely. Based on the results, the complete remission in all four follow-up stages was significantly higher in silymarin group than the placebo group: Week 1 (intervention: 9 (22.5%), control: 0 (0%), (p=0.011), week 2 (intervention group: 18 (45%), placebo: 7 (17.5%), (p=0.000), week 3 (intervention: 24 (60%), placebo: 11 ( 27.5%), (p=0.051); week 4 (intervention: 27 (67.5%), control: 19 (47.5%), (p=0.003).Conclusions:According to our results, the 4-week adjuvant treatment with oral silymarin resulted in the full and faster wound recovery in patients with second degree-burn. So, it is recommended to use adjuvant treatments to obtain effective results.

Clinical characteristics and outcome of toxicity from Amanita mushroom poisoning.

ObjectiveTo describe and analyze the clinical characteristics and outcome of amatoxin poisoning cases.MethodsWe performed a retrospective cohort study of amatoxin poisoning cases from Ramathibodi Poison Center Toxic Exposure Surveillance System, from May 2013 to August 2015.ResultsThere were 30 consultations with a total of 55 poisoning cases. Most cases were male and from the north-east region. Hepatitis, acute kidney injury, jaundice, and coagulopathy accounted for 74%, 46.3%, 44.7%, and 52.8% of the cases, respectively. Almost all of the patients were admitted to the hospital, and the median duration of hospital stay was found to be 4 days. Mortality rate was found to be 27.3%. Most patients (73%) received the treatment including multiple-dose activated charcoal (67.5%), intravenous N-acetylcysteine (87.5%), and benzylpenicillin (45%). In 60% of the cases, the treatment was initiated within 24 h after eating mushrooms. Exchange transfusion and liver transplantation were performed in one severe case. However, this patient died eventually. Because intravenous silybinin is not available in Thailand during the study period, 8 patients received oral silymarin instead. All 8 patients had hepatitis and were treated with high dosage of oral silymarin (5 patients with 4.48 g/day, 2 patients with 1.68 g/day, and 1 patient with 1.4 g/day) for a couple of days. One of these patients died as she received treatment very late; she was treated with silymarin at 1.68 g/day dosage. Thus, the fatality in oral silymarin treatment group was 12.5%. We performed the analysis between the dead and survival groups. We found that in hepatitis, initial and maximum serum aspartate transaminase, initial and maximum serum alanine transaminase, and acute kidney injury were significantly different between the two groups.ConclusionAmanita mushroom poisoning caused high fatalities. Serum transaminase and creatinine were the factors associated with death. Treatment with oral high dose silymarin should be investigated further as one of the principal therapies in amatoxin poisoning.

ASSESSMENT OF CURATIVE EFFECT OF USING STEM CELLS ON THE CONTROL OF PESTICIDE DAMAGING EFFECT ON LIVER

causes of death worldwide. Regenerative medicine as stem cells therapy is a newly rapidly developing field in which diseased tissues are regenerated. Aim: To evaluate the effectiveness of stem cell on liver degeneration induced by Chlorpyrifos as an organophosphorus insecticide widely used in agriculture in Egypt, and Comparing its efficacy with silymarin and colchicine as antifibrotic agents used in liver fibrosis. Methods: Induction of liver degeneration and fibrosis by Chlorpyrifos (CPF) for 8 weeks to Swiss albino mice in randomly divided groups (B, C and D) and a control healthy group (A), each group composed of 15 mice. Group (C) was treated with oral silymarin and colchicine and group (D) was treated with intra-peritoneal injection of Mesenchymal stem cells (MSC) (10 6 cells / mouse) after induction of liver fibrosis. After 4 weeks of treatment, all mice were sacrificed, blood was collected for chemical analysis (liver functions tests: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Albumin, Bilirubin). Histopathological evaluation and grading were assessed by H& E stain. Results: ALT, AST and Albumin were significantly improved in groups C and D. Bilirubin and liver tissue grading were significantly reduced in group D, with insignificant reduction in group C. Conclusion: Treatment with MSCs may improve liver functions tests (ALT, AST, Albumin, and Bilirubin) and liver fibrosis. While, treatment with colchicine and silymarin does not improve the liver fibrosis, nor improves total serum bilirubin, but may improve ALT, AST and Albumin.

HEPATOTOXICITY;

Objectives: To evaluate the protective role of silymarin against methotrexate(MTX) induced hepatotoxicity in mice. Study design: Randomized controlled trial on animalmodel. Period: 06 months from March 2016 to August 2016. Settings: Department ofPharmacology and Therapeutics, Army Medical College, Rawalpindi. Material and Methods:Thirty male BALB/c mice were randomly divided into five groups (n=6). Group A received 0.2 mlnormal saline intraperitoneally served as control for MTX. Group B received 0.2 ml distilled waterorally for 7 days served as control for oral silymarin. Group C received single intraperitonealinjection of MTX 20 mg/kg. Group D received silymarin 25 mg/kg orally for seven days. GroupE received silymarin 25 mg/kg orally for 7 days with MTX 20 mg/kg intraperitoneally at day 4.Blood samples for measuring serum ALT (Alanine Transaminase), AST (Aspartate transaminase)and ALP (Alkaline Phosphatase) along with liver samples for hepatic histological examinationwere taken after 24 hours of last dose. Results: Silymarin show hepatoprotective effect againstMTX induced hepatotoxicity. Conclusion: Silymarin has hepatoprotective potential whenadministered along with MTX.