Silymarin's defensive role against hepatotoxicity induced by amiodarone in albino rats / El efecto defensivo de silimarin contra la hepatotoxicidad inducida por amiodarona en ratas albinas

SUMMARY: Amiodarone (AMD), an orally powerful antidysrhythmic medication that has caused hepatotoxicity on long-term administration, is commonly used across the world. Silymarin ameliorative effects (SLM); this research elucidated the magnitude of the damage to the liver tissue in AMD. We divided 24 albino rats evenly into four groups given daily doses by gastric tube for eight weeks as follows; the 1st group acted as a control group; the 2nd group received SLM; the 3rd group received AMD; and the 4th group received AMD parallel to SLM. Liver tissues prepared for light, electron microscopic and serum samples screened for biomarkers (I)liver injury enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST); (II) oxidative and antioxidant stress, malondialdehyde (MDA) and superoxide dismutase (SOD); and (III) inflammatory markers, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6). The findings showed that AMD caused hepatic histological changes that included congestion of the blood vessels, leucocytic infiltration and cytoplasmic vacuolation. Ultrastructural degeneration of the mitochondria, endoplasmic reticulum swelling, nuclear pyknosis and increased fat droplets and lysosomes were observed. The biochemical findings showed an increase in the AMD group's ALT and AST activities. The group of rats treated with AMD and SLM, increased the improvements in histology and ultrastructure, while the ALT and AST levels were reduced. Our findings collectively agreed that SLM has a protective impact on AMD hepatotoxicity which can be due to its antioxidant properties.

RESUMEN: La amiodarona (AMD) es un fuerte medicamento antiarrítmico administrado por vía oral que ha causado hepatotoxicidad en la administración a largo plazo utilizado con frecuencia en todo el mundo. Efectos de mejora de la silimarina (SLM); esta investigación analizó la magnitud del daño al tejido hepático en la DMAE. Dividimos 24 ratas albinas de manera uniforme en cuatro grupos que recibieron dosis diarias por sonda gástrica durante ocho semanas de la siguiente manera; el primer grupo fue designado como grupo control; el segundo grupo recibió SLM; el tercer grupo recibió AMD; y el cuarto grupo recibió AMD en paralelo a SLM. Se prepararon tejidos hepáticos para muestras de suero, microscopía de luz y electrónica y se analizaron para biomarcadores (I) enzimas de daño hepático, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST); (II) estrés oxidativo y antioxidante, malondialdehído (MDA) y superóxido dismutasa (SOD); y (III) marcadores inflamatorios, factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6). Los hallazgos mostraron que la DMAE genera cambios histológicos hepáticos que incluyen congestión de los vasos sanguíneos, infiltración leucocítica y vacuolación citoplásmica. Se observó una degeneración ultraestructural de las mitocondrias, aumento del retículo endoplásmico, picnosis nuclear y aumento de gotitas de grasa y lisosomas. Los hallazgos bioquímicos mostraron un aumento en las actividades de ALT y AST del grupo AMD. El grupo de ratas tratadas con AMD y SLM, aumentó las mejoras en histología y ultraestructura, mientras que se redujeron los niveles de ALT y AST. Nuestros hallazgos coincidieron colectivamente en que SLM tiene un impacto protector sobre la hepatotoxicidad de AMD debido a sus propiedades antioxidantes.

Role of ascorbic acid versus silymarin in amelioration of hepatotoxicity induced by acrylamide in adult male albino rats: histological and immunohistochemical study / Rol del ácido ascórbico frente a la silimarina en la mejoría de la hepatotoxicidad inducida por acrilamida en ratas albinas macho adultas: estudio histológico e inmunohistoquímico

SUMMARY: Acrylamide (ACR) is a cytotoxic and carcinogenic material. It is a product of a Maillard reaction during the cooking of many types of fried fast food, e.g. potato chip fries, and chicken nuggets. ACR has a severe toxic effect on different body organs. This study investigates the hepatotoxic effect of ACR, and the protective effect of ascorbic acid and silymarin. For this purpose, forty adult, male, albino rats were divided into four groups and received the following treatments for fourteen days: Group I: (the control) normal saline; Group II: ACR only; Group III: ACR and ascorbic acid; and Group IV: ACR and silymarin. Under a light microscope, the liver from rats treated with ACR only presented disturbed liver architecture, degenerated hepatocytes, reduced glycogen contents, congested central vein, and increased collagen fibres with areas of fibrosis. Immunohistochemical examination revealed an increased mean number of CD68-, and α-SMA-positive cells. This indicates the presence of large numbers of stellate macrophages (Kupffer cells) and Hepatic stellate cells (HSCs). The combination of ACR with either ascorbic acid or silymarin resulted in less hepatic degeneration, less fibrosis and fewer CD68 and α-SMA positive cells compared to the ACR only group. In conclusion, treatment with silymarin or ascorbic acid along with ACR appears to alleviate ACR-induced hepatotoxicity with more protection in silymarin treated rats.

RESUMEN: La acrilamida (ACR) es un material citotóxico y cancerígeno. Es producto de la reacción de Maillard durante la cocción de muchos tipos de comida rápida y frita, por ejemplo: papas fritas y nuggets de pollo. ACR tiene un efecto tóxico severo en diferentes órganos del cuerpo. Este estudio investigó el efecto hepatotóxico del ACR y el efecto protector del ácido ascórbico y la silimarina. Con este fin, cuarenta ratas albinas machos adultas se dividieron en cuatro grupos y recibieron los siguientes tratamientos durante catorce días: Grupo I (control), solución salina normal; Grupo II, solo ACR; Grupo III, ACR y ácido ascórbico; y Grupo IV, ACR y silimarina. Bajo microscopio óptico, el hígado de ratas tratadas con ACR solo presentó alteración de su arquitectura, entre ellos hepatocitos degenerados, contenido reducido de glucógeno, vena central congestionada y aumento de fibras de colágeno con áreas de fibrosis. El examen inmunohistoquímico reveló un aumento del número medio de células CD68 y α-SMA positivas. Esto indica la presencia de un gran número de macrófagos estrellados (células de Kupffer) y células estrelladas hepáticas (HSC). La combinación de ACR con ácido ascórbico o silimarina resultó en menos degeneración hepática, menos fibrosis y menos células positivas para CD68 y α-SMA en comparación con el grupo de ACR solo. En conclusión, el tratamiento con silimarina o ácido ascórbico junto con ACR parece aliviar la hepatotoxicidad inducida por ACR.

Citral effect in male NMRI mice nonalcoholic steatosis model: assessing biochemical and histological parameters and PPARα gene expression

Citral is a small molecule present in various citrus species, with reported anti-hyperlipidemic and anti-inflammation effects. Here, the effect of intraperitoneal (IP) administration of citral is evaluated in a mouse model of non-alcoholic steatosis. Male NMRI mice were divided into the following groups (n = 12): normal control group (NC) receiving a normal diet; high-fat emulsion group (HF) receiving high fat diet for four weeks; positive control group (C+) receiving HF diet for four weeks and then shifted to normal diet with IP-administered silymarin (80 mg/kg) for four weeks; sham group receiving HF diet for four weeks and then shifted to normal diet for four weeks; and EC1, EC2, and EC3 groups receiving HF diet for four weeks and then shifted to normal diet with IP-administered citral doses of 5, 10, and 20 mg/kg, respectively. HF diet resulted in steatohepatitis with impaired lipid profile, high glucose levels and insulin resistance, impaired liver enzymes, antioxidants, adiponectin and leptin levels, decreased PPARα level, and fibrosis in the liver tissue. Upon treatment with citral, improvement in condition was observed in a dose-dependent manner-both at histological level and in the serum of treated animals. and the PPARα level was also increased.

Anti-inflammatory effect of silymarin on ovarian immunohistochemical localization of TNF-alpha associated with systemic inflammation in polycystic ovarian syndrome / Efecto antiinflamatorio de la silimarina en la localización inmunohistoquímica ovárica del TNF-alfa asociado con la inflamación sistémica en el síndrome de ovario poliquístico

Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.

El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.

Effect of silymarin on oxidative stress and liver histopathology in experimental obstructive jaundice model

ABSTRACT PURPOSE: To investigate the effect of silymarin on oxidative stress and hepatic injury induced by obstructive jaundice in an experimental model. METHODS: Thirty Wistar-Albino type female rats were divided into 3 groups each including 10 rats. Only laparotomy was performed in group 1. Bile duct ligation was performed in group 2. In group 3, bile duct ligation was performed and orogastic silymarin 300 mg/kg/day dose was given for seven days. At the end of seven days, rats were sacrificed. The blood and liver tissue samples were taken to be examined biochemically and histopathologically. RESULTS: The plasma and liver levels of malondialdehyde were significantly lower in silymarin group than in the bile duct ligated group. Although liver levels of GSH were significantly higher in silymarin group than in the bile duct ligated group, there was no significant difference between the plasma GSH levels of these groups. In silymarin group; the enlargement of hepatocytes, dilatation of canaliculi and the edema were regressed. CONCLUSION: Silymarin diminished the harmful effects of obstructive jaundice on liver.

Antioxidant effect of Legalon(r) SIL in ischemia-reperfusion injury of rat skeletal muscle

PURPOSE: To evaluated the potential antioxidant agent Legalon (r) SIL (silibinin-C-2',3-bis(hydrogensuccinat)) in the skeletal muscle of rats. METHODS: IRI was achieved via tourniquet application in Wistar-albino rats. Experimental groups were chosen as (i) sham control, (ii) IRI (3+2 h), (iii) IRI and Legalon (r) SIL-50 (50 mg/kg/i.p.), (iv) IRI and Legalon (r) SIL-100 (100 mg/kg/i.p.), and (v) IRI and Legalon (r) SIL-200 (200 mg/kg/ i.p.). Muscle viability (evaluated by triphenyltetrazolium chloride dye method), malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were assessed in muscle samples using a spectrophotometer. RESULTS: Although viability of the injured limb non-significantly declined in the IRI group, administration of Legalon (r) SIL did not prevent injury. However, dramatic increase observed in malondialdehyde levels in the IRI group was prohibited by Legalon (r) SIL in a statistically significant manner. In comparison with the sham-control group, IRI and Legalon (r) SIL administration did not cause any significant alterations in the levels of superoxide dismutase, catalase, and glutathione peroxidase. CONCLUSION: Although Legalon (r) SIL was not sufficient to prevent muscle injury in terms of viability, it is found to be an effective option to reduce reactive oxygen species-induced cell injury.

Cytotoxicity and hepatoprotective attributes of methanolic extract of Rumex vesicarius L

BACKGROUND: To evaluate the hepatoprotective potential and invitro cytotoxicity studies of whole plant methanol extract of Rumex vesicarius L. Methanol extract at a dose of 100 mg/kg bw and 200 mg/kg bw were assessed for its hepatoprotective potential against CCl4-induced hepatotoxicity by monitoring activity levels of SGOT (Serum glutamic oxaloacetic transaminase), SGPT (Serum glutamic pyruvic transaminase), ALP (Alkaline phosphatase), TP (Total protein), TB (Total bilirubin) and SOD (Superoxide dismutase), CAT (Catalase), MDA (Malondialdehyde). The cytotoxicity of the same extract on HepG2 cell lines were also assessed using MTT assay method at the concentration of 62.5, 125, 250, 500 µg/ml. RESULTS: Pretreatment of animals with whole plant methanol extracts of Rumex vesicarius L. significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver. The biochemical parameters in serum also improved in treated groups compared to the control and standard (silymarin) groups. Histopathological investigation further corroborated these biochemical observations. The cytotoxicity results indicated that the plant extract which were inhibitory to the proliferation of HepG2 cell line with IC50 value of 563.33 ± 0.8 Mg/ml were not cytotoxic and appears to be safe. CONCLUSIONS: Rumex vesicarius L. whole plant methanol extract exhibit hepatoprotective activity. However the cytotoxicity in HepG2 is inexplicable and warrants further study.

Combined treatment with silibinin and either sorafenib or gefitinib enhances their growth-inhibiting effects in hepatocellular carcinoma cells

BACKGROUND/AIMS: Silibinin, the main component of silymarin, is used as a hepatoprotectant and exhibits anticancer effects against various cancer cells. This study evaluated the effects of a combination of silibinin with either gefitinib or sorafenib on hepatocellular carcinoma (HCC) cells. METHODS: Several different human HCC cell lines were used to test the growth-inhibiting effects and cell toxicity of silibinin both alone and in combination with either gefitinib or sorafenib. The cell viability and growth inhibition were assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue staining, and a colony-forming assay. Furthermore, changes in epidermal growth factor receptor (EGFR)-related signals were evaluated by Western blot analysis. RESULTS: Gefitinib, sorafenib, and silibinin individually exhibited dose-dependent antiproliferative effects on HCC cells. Combined treatment with silibinin enhanced the gefitinib-induced growth-inhibiting effects in some HCC cell lines. The combination effect of gefitinib and silibinin was synergistic in the SNU761 cell line, but was only additive in the Huh-BAT cell line. The combination effect may be attributable to inhibition of EGFR-dependent Akt signaling. Enhanced growth-inhibiting effects were also observed in HCC cells treated with a combination of sorafenib and silibinin. CONCLUSIONS: Combined treatment with silibinin enhanced the growth-inhibiting effects of both gefitinib and sorafenib. Therefore, the combination of silibinin with either sorafenib or gefitinib could be a useful treatment approach for HCC in the future.

Protective effects of silymarin on fumonisin B1-induced hepatotoxicity in mice

The present study was conducted to investigate the effect of silymarin on experimental liver toxication induced by Fumonisin B1 (FB1) in BALB/c mice. The mice were divided into six groups (n = 15). Group 1 served as the control. Group 2 was the silymarin control (100 mg/kg by gavage). Groups 3 and 4 were treated with FB1 (Group 3, 1.5 mg/kg FB1, intraperitoneally; and Group 4, 4.5 mg/kg FB1). Group 5 received FB1 (1.5 mg/kg) and silymarin (100 mg/kg), and Group 6 was given a higher dose of FB1 (4.5 mg/kg FB1) with silymarin (100 mg/kg). Silymarin treatment significantly decreased (p < 0.0001) the apoptotic rate. FB1 administration significantly increased (p < 0.0001) proliferating cell nuclear antigen and Ki-67 expression. Furthermore, FB1 elevated the levels of caspase-8 and tumor necrosis factor-alpha mediators while silymarin significantly reduced (p < 0.0001) the expression of these factors. Vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) expressions were significantly elevated in Group 4 (p < 0.0001). Silymarin administration alleviated increased VEGF and FGF-2 expression levels (p < 0.0001). In conclusion, silymarin ameliorated toxic liver damage caused by FB1 in BALB/c mice.

Effect and the probable mechanisms of silibinin in regulating insulin resistance in the liver of rats with non-alcoholic fatty liver

Our previous study has shown that reduced insulin resistance (IR) was one of the possible mechanisms for the therapeutic effect of silibinin on non-alcoholic fatty liver disease (NAFLD) in rats. In the present study, we investigated the pathways of silibinin in regulating hepatic glucose production and IR amelioration. Forty-five 4- to 6-week-old male Sprague Dawley rats were divided into a control group, an HFD group (high-fat diet for 6 weeks) and an HFD + silibinin group (high-fat diet + 0.5 mg kg-1·day-1 silibinin, starting at the beginning of the protocol). Both subcutaneous and visceral fat was measured. Homeostasis model assessment-IR index (HOMA-IR), intraperitoneal glucose tolerance test and insulin tolerance test (ITT) were performed. The expression of adipose triglyceride lipase (ATGL) and of genes associated with hepatic gluconeogenesis was evaluated. Silibinin intervention significantly protected liver function, down-regulated serum fat, and improved IR, as shown by decreased HOMA-IR and increased ITT slope. Silibinin markedly prevented visceral obesity by reducing visceral fat, enhanced lipolysis by up-regulating ATGL expression and inhibited gluconeogenesis by down-regulating associated genes such as Forkhead box O1, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Silibinin was effective in ameliorating IR in NAFLD rats. Reduction of visceral obesity, enhancement of lipolysis and inhibition of gluconeogenesis might be the underlying mechanisms.

Effects of silibinin and ethanol on skeletal muscle ischemia-reperfusion injury

PURPOSE: To investigate the potential beneficial effect of silibinin in ischemia-reperfusion injury (IRI) of skeletal muscle. METHODS: Under urethane anesthesia, four experimental groups were established in Balb/c mice: I) Sham-control, II) IRI (Tourniquet-induced) (2+1 h), III) IRI+ethanol (10%), and IV) IRI+silibinin (50 mg/kg/IP). The viability of muscle (left) was evaluated by the triphenyltetrazolium chloride dye method and calculated as the percentage of the contralateral control muscle (right). Malondialdehyde, superoxide dismutase, and catalase were measured in the gastrocnemius muscle via a spectrophotometer. RESULTS:The viability of gastrocnemius muscle in group II was significantly lower in comparison with that seen in group I. The administration of either ethanol or silibinin rendered the tissues to recover nearly to the baseline level. Additionally, malondialdehyde levels were higher in group II than those in group I. The application of silibinin prior to the reperfusion attenuated these to the control levels. However, malondialdehyde levels in the ethanol administrated group were reduced as well. The enhanced superoxide dismutase activity seen in the IRI group was not diminished in the animals treated with either silibinin or ethanol. Similarly, there were no differences between groups regarding the catalase activities. CONCLUSION: Ethanol seems to be effective in attenuating IRI in skeletal muscle and no definite conclusion can be made on silibinin effect.

Study of the hepatoprotective effect of Juniperus phoenicea constituents

Different fraction obtained from the aerial parts of Juniperus phoenicea showed significant activity as hepatoprotective when investigated against carbon tetrachloride induced liver injury. The hepatoprotective activity was evaluated through the quantification of biochemical parameters and confirmed using histopathology study. Phytochemical investigation of the petroleum ether, chloroform and methanol fractions utilizing different chromatographic techniques resulted in the isolation of five known diterpenoids namely: 13-epicupressic acid [1], imbricatolic acid [2], 7 alpha -hydroxysandaracopimaric acid [3], 3 beta -hydroxysandaracopimaric acid [4], isopimaric acid [5], four flavonoid derivatives: cupressuflavone [6], hinokiflavone [7], hypolaetin-7-O- beta -xylopyranoside [9], [-] catechin [10], inaddition to sucrose [8]. Both physical and spectral data were used for structure determination and all isolates were evaluated for their hepatoprotective activity. Compounds 2 and 6 were effective, however; 7 was the most active. Hepatoprotective activity of 7 is comparable with the standard drug silymarin in reducing the elevated liver enzymes and restoring normal appearance of hepatocytes. Hepatoprotective effect of combination of 6, 7 and silymarin with the diterpene sugiol was also explored

Hepatoprotective studies on haloxylon salicornicum: a plant from cholistan desert

The objective was to study the in-vivo hepatoprotective effect of aerial parts vi Haloxylon salicornicum [Moq.] Bunge [Family: Chenopodiaceae] in order to validate its traditional use in hepatobiliary disorders, by native people of Cholistan desert, Pakistan. Aerial parts [ethanolic extract] ofHaloxylon salicornicum [HS], [500 and 750 mg/kg/day, p.o. for 7 days] were evaluated on CC1[4] intoxicated rabbits [0.75 ml/kg., s/c.] by serum biochemical parameters and liver histopathological observations. Silymarin [100 mg/kg/day, p.o. for 7 days] was used as a standard hepatoprotective drug. CC1[4] intoxicated group had elevated levels of SCOT, SGPT and ALP significantly but TB level was normal as compared to control group. HS extract [both doses of 500 and 750 mg/kg] showed hepatoprotective effect by significant restoration of SCOT, SGPT, ALP and TB levels as compared to CC1[4] control. 500 mg/kg doses of HS extract produced more significant results as compared to 750 mg/kg doses and Silymarin. Histopathological examination of liver tissues further substantiated these findings. Therefore, outcome of the present study validate the traditional claims on hepatoprotective effects ofHaloxylon salicornicum [aerial parts]

Anti-inflammatory activity of silymarin in patients with knee osteoarthritis. A comparative study with piromcam and meloxicam

To evaluate the anti-inflammatory effect of Silymarin in patients with knee osteoarthritis OA in comparison with piroxicam and meloxicam. A double-blind clinical trial was performed at the Department of Rheumatology, Baghdad Teaching Hospital, Baghdad, Iraq during the period from October 2004 to September 2005, in which 220 patients 79 males and 141 females with painful knee osteoarthritis were randomized into 5 groups, treated with either silymarin 300mg/day, piroxicam 20mg/day, meloxicam 15mg, or a combination of silymarin with piroxicam or meloxicam. Serum levels of interleukin-1 alpha, interleukin-8, and the complement proteins C3 and C4 were assessed at zero time, and after 8 weeks. Silymarin reduces significantly serum levels of IL-1 alpha and IL-8, C3 and C4 after 8 weeks compared to the pre-treatment levels. Piroxicam showed no significant reduction in IL-1 alpha levels, while IL-8 decreased significantly, compared to pre-treatment value. Meloxicam elevates serum levels of IL-1 alpha significantly, while IL-8 did not significantly change compared to the pre-treatment value. Piroxicam or meloxicam produced slight, non-significant increase in serum levels of complement proteins after the 8-week treatment period. Adjunct use of silymarin with piroxicam results in significant reduction in both cytokines IL-1 alpha and IL-8, and serum levels of C3 and C4. However, its adjunct use with, meloxicam did not reveal any significant changes in this respect. Silymarin reduces the elevated levels of interleukins and complement proteins, when used alone, or in combination with NSAIDs for the treatment of knee OA

Antioxidant activity of Aulosira fertilisima on CCl4 induced hepatotoxicity in rats.

Free radicals cause cell injury, when they are generated in excess or when the antioxidant defense is impaired. Carbon tetrachloride (CCl4) is used as a model for liver injury. In this study antioxidant activity of ethanol extract of A. fertilisima (EEA) was investigated using CCl4 intoxicated rat liver as the experimental model. Oral administration of EEA at a dose of 100 mg/kg body weight, for 14 consecutive days, the rate of the production of antioxidant enzymes like super oxide dismutase, catalase, glutathione peroxidase and glutathione transferase in rats compared to the CCl4 treated group without any supporting treatment. Liver damage is detected by the measurement of the activities of serum enzymes like aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase and alkaline phosphatase which were released in to the blood from damaged cells. The normalization of these enzymes levels was observed in rats treated with EEA (100 mg/kg body weight) by reducing the leakage of the above enzymes in to the blood. The findings provide a rationale for further studies on isolation of active principles and its pharmacological evaluation. Protection offered by silymarin (standard reference drug) seemed relatively greater.

Study on effects of topical use of Silybum marianum extract [silymarin] on U.V. irradiated guinea pig skin

Regarding to the skin damages caused by the ultraviolet ray of sun and the need for protective materials against these mal effects, Silymarin was evaluated for the porpose. In this study, by histopathology studies and surveying the clinical symptoms the external use of an herbaceous [herbal] substance, Silymarin, in protecting the mal effects of ultraviolet ray has been evaluated. For the study 60 albino hamsters with same age and gender has been selected and they divided in two groups [each group 30 hamsters] randomly. The hair on the back of all animals shaved in an area about 2 square centimeters. The first group gets 9 miligram Silymarin with 20 micro liter acetone topically, and the second group gets only 20 micro liter acetone topically. Then both groups for 45 days exposed to ultra violet ray, 180 milijoule/cm[2] each day. The results of clinical and histopathologic surveys show that topical usage of Silymarin has considerable protective effects against the mal effects of ultra violet ray on skin and this can be a promise for using this herbaceous substance as a topical sun protects substance

Protective effects of silymarin, a milk thistle (Silybium marianum) derivative on ethanol-induced oxidative stress in liver.

The production of reactive oxygen species (ROS) is considered to be a major factor in oxidative cell injury. The antioxidant activity or the inhibition of the generation of free radicals is important in providing protection against such hepatic damage. Silymarin, derived from the milk thistle plant, Silybium marianum, has been used in traditional medicine as a remedy for diseases of the liver and biliary tract. In the present study, the effect of hepatoprotective drug silymarin on body weight and biochemical parameters, particularly, antioxidant status of ethanol-exposed rats was studied and its efficacy was compared with the potent antioxidant, ascorbic acid as well as capacity of hepatic regeneration during abstention. Ethanol, at a dose of 1.6 g/kg body wt/day for 4 wks affected body weight in 16-18 week-old male albino rats (Wistar strain weighing 200-220 g). Thiobarbituric acid reactive substance (TBARS) level, superoxide dismutase (SOD), and glutathione-s-transferase (GST) activities were significantly increased, whereas GSH content, and catalase, glutathione reductase (GR) and GPx (glutathione peroxidase) activities significantly reduced, on ethanol exposure. These changes were reversed by silybin and ascorbic acid treatment. It was also observed that abstinence from ethanol might help in hepatic regeneration. Silybin showed a significant hepatoprotective activity, but activity was less than that of ascorbic acid. Furthermore, preventive measures were more effective than curative treatment.

Dose-dependent protective effects of silymarin against ccu-induced liver damage in rats

Silymarin, the dried extract of the ripe seeds of Silybum marianum is found to be a powerful protective agent against xenobiotics-induced tissue injury in many organs, including liver. However, the dose-dependent relationship of this effect and tissue availability is not fully explored. So, this project was designed to evaluate the relationship between dose, tissue availability and tissue protection of silymarin against ccu-induced hepatic toxicity in rats. The tissue protective effects of silymarin were studied through the pre-treatment of rats with various doses [250, 500, and l000 mg/kg] orally twice daily before the induction of hepatotoxicity of ccl4. Malondialdehyde [MDA] and glutathione [GSH] were evaluated in the serum and tissue homogenate. The activities of different enzymes, which are considered as indicators of organ toxicity like alanine amino transaminase [ALT] and aspartate aminotransaminase [AST] were assessed. Histopathological examination of stained tissue sections from the liver were done to evaluate the protective effect at the microscopical levels. In addition, silymarin level in liver tissue homogenate -was evaluated using HPLC method. The data obtained indicated that, a significant amelioration of oxidative stress experimentally induced in the liver of rats was produced by silymarin, as evidenced by lowering MDA contents and elevation of GSH levels both in the tissues and serum compared with controls. Serum activities of ALT and AST were normalized. Additionally, histologically evident damage in the liver had improved In addition, increasing silymarin dose after oral administration resulted in increased tissue availability of many constituents. There is a dose-dependent relationship in the hepatoprotective effect of silymarin against ccU-induced hepatotoxicity in rats

effect of different doses of silymarin on gentamicin-induced kidney damage in rats

Many in vivo and in vitro studies performed mainly in liver have been shown silymarin to be a potent anti-oxidant, and one of the most potent scavengers of hydroxyl radicals. Therefore, it is plausible to expect that it may produce these effects against oxidalive stress consequences induced by gentamicin in the kidney. Evaluation of the protective effect of different doses of silymarin given orally in protecting rats against gentamicin-induced nephrotoxicity. Groups of rats [6 rats each] were pre-treated for 7 days with 250, 500, and l000 mg/kg silymarin and vehicle orally before induction of renal toxicity with gentamicin, and another 6 rats were utilized as controls. The parameters of oxidative stress, malondialdehyde [MDA], and glutathione [GSH] were measured in the serum and kidney tissue homogenate, in addition to serum levels of urea and creatinine. Histopathological examination of stained tissue sections from the kidney was performed; in addition to silymarin level in the kidney tissue homogenate was evaluated using HPLC method. Analysis of data revealed significant amelioration of oxidative stress, experimentally induced in the kidney through lowering MDA and elevation of GSH levels, both in serum and tissue homogenate, associated with significant reduction of serum levels of urea and creatinine, and with positive histological evidences for the protective effect of silymarin which is found to be related to the increase in its renal tissue availability when the oral dose was increased. These findings suggest that, silymarin is effective in preventing gentamicin-induced renal toxicity, which makes it a good candidate for clinical use in this respect

Light and electron microscopic study on the hepatoprotective effect of silymarin on potentially fatty infiltrated liver during pregnancy in albino rats

Preservation of the mother health and fetal life during pregnancy is the major task of obstetricians. Though pregnancy is a great burden over the vital organs, it influences and influenced by the functions of these organs. Most common forms of liver changes during pregnancy are reversible, but some serious illness as fatty infiltration of the liver with pregnancy may develop and threaten the life of the mother to a degree that termination of pregnancy appears to be the only solution to save her life. The present study investigated the structural changes of the liver of young adult female albino rats during pregnancy and compared them with the corresponding findings after administration of silymarin, a hepatoprotective agent, during pregnancy. Thirty adult female albino rats, three months old, were used in this study. Ten of them were used as a control group, while the other twenty rats were divided into two experimental groups, ten rats each. Animals of the first group were subjected to pregnancy, while animals of the other experimental group received the heptoprotective agent, silymarin, at a dose 2.5 mg dissolved in saline once daily throughout their pregnancy. Liver samples of both groups were examined by light and transmission electron microscopes comparing the findings with the liver samples of control rats. Light microscopic examination of liver specimens during pregnancy revealed mild degree of cellular infiltration around the congested sinusoids and mild cytoplasmic vacuolations. The electron microscopic study clarified accumulation of lipid droplets and secondary lysosomes, mitochondrial degene ration, abundance of rough endoplasmic reticulum and marked proliferation and vesiculation of smooth endoplasmic reticulum.Disfigurement of nuclear outline together with chromatin clumping and peripheral migration of the nucleolus were observed. Also the bile canaliculi appeared dilated. Light microscopic examination of treated liver with the hepatoprotective agent, silymarin, during pregnancy revealed absence of cellular infiltration and sinusoidal congestion but demonstrated minimal cytoplasmic vacuolations. The electron microscopic study of the hepatocytes clarified absence or mild deposition of lipid droplets, restoration of mitochondrial integrity, mild proliferation of smooth endoplasmic reticulum, apparently normal rough endoplasmic reticulum, less degree of chromatin clumping and approximately central nucleolus. The absence of cellular infiltration and the minimal degree of degeneration affecting the hepatocytes and preservation of integrity of hepatocyte organelles in the treated liver with silymarin proved the hepatoprotective role of this agent, even, with the stress condition of pregnancy