Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats

Abstract Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferronis post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

Resumo As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

In vivo pharmacokinetics and in vitro-in vivo correlation of silymarin phospholipid complex microporous osmotic pump controlled-release tablets in beagle dogs / 药学实践杂志

Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.

Study on inhibitory effects and mechanism of silymarin on glioma in vivo and in vitro / 中国药房

OBJECTIVE To investigate the inhibitory effects of silymarin （SM） on glioma in vivo and in vitro and its potential mechanism. METHODS Human glioma cell line U87 cells were randomly divided into control group， SM low- concentration， SM medium-concentration and SM high-concentration groups （50， 100， 200 μg/mL）， protein kinase B （Akt） activator group （SC79 20 μmol/L）， high-concentration of SM combined with Akt activator group （SM 200 μg/mL+SC79 20 μmol/L）. After drug treatment （except for the control group）， optical density （OD） value， clone formation rate， apoptotic rate， the expressions of proliferation/apoptosis-related proteins [proliferating cell nuclear antigen （PCNA）， B-cell lymphoma-2 （Bcl-2）， Bcl- 2-associated X protein （Bax）， caspase-3]， the phosphorylation levels of Akt/mitogen-activated protein kinase （MAPK） signaling pathway related proteins [Akt， p38 MAPK， extracellular signal-regulated kinase 1/2 （ERK1/2）] were detected in each group. The xenograft tumor model in nude mice was established by injecting U87 cells subcutaneously via the right armpit， and then divided into control group， SM low-dose， SM medium-dose and SM high-dose groups （25， 50， 100 mg/kg）， Akt activator group （SC79 40 mg/kg）， high-dose of SM combined with Akt activator group （SM 100 mg/kg+SC79 40 mg/kg）， with 5 mice in each group. After drug intervention （except for the control group of nude mice）， the tumor mass was weighed and the tumor volume was calculated. RESULTS Compared with control group， the OD values， clone formation rates， protein expressions of PCNA and Bcl- 2， phosphorylation levels of Akt， p38 MAPK and ERK1/2 in SM groups， tumor mass and volume in nude mice of SM groups were all decreased significantly， while the apoptosis rates， protein expressions of Bax and caspase-3 were increased significantly， in a dose-dependent manner （P＜0.05）；the trend of changes in the above indicators in the Akt activator group was opposite （P＜ 0.05）， and Akt activator could significantly attenuate the inhibitory effect of high-concentration/high-dose SM on glioma in vivo and in vitro （P＜0.05）. CONCLUSIONS SM may promote the apoptosis of U87 cells， and inhibit its proliferation， clone formation and tumor growth in xenograft nude mice by inhibiting Akt/MAPK signaling pathway.

Hepatoprotective effect of obeticholic acid on acetaminophen induced hepatotoxicity in mice

Acetaminophen (APAP) is commonly used as analgesic and antipyretic drug for relieving mild and moderate pain, but at high doses produces hepatic necrosis. Though, Obeticholic acid (OCA) has been tested in range of diseases, its therapeutic potential against APAP-induced hepatic injury remains to be elucidated. Thus, in this study, we investigated the preventive effect of OCA along with N-acetylcysteine (NAC) and Silymarin (SIL) against acetaminophen-induced hepatotoxicity in mice. SIL (100 mg/kg, po) and OCA (30 mg/kg, po) were administered continuously for six days prior to APAP administration. After sixth dose, animas were fasted for 12 h and treated with 300 mg/kg APAP and then received SIL (100 mg/kg, po), NAC (500 mg/kg, ip) and OCA (30 mg/kg, po) at 1 h after APAP. Mice were sacrificed 6 h after APAP injection. Analysis of serum Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), liver glutathione (GSH) and histopathology were employed for assessment of hepatotoxicity. APAP group showed a significant increase in ALT, AST, ALP and centriolobular hepatic necrosis with a significant decrease in glutathione in comparison to control group. All these parameters were significantly improved in all the three treated groups when compared to APAP group. In conclusion, Obeticholic acid (OCA), Silymarin (SIL) and N-acetylcysteine (NAC) are suggested to protect against APAP-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect and decreasing liver necrosis.

Bioavailability augmentation of silymarin using natural bioenhancers: An in vivo pharmacokinetic study

Abstract Pharmacokinetic studies were carried out in male and female rats to quantify silymarin as silybin (A+B) after the oral administration of various silymarin formulations combined with three bioenhancers, namely, lysergol, piperine, and fulvic acid, and compared with plain silymarin formulation (control). A non-compartmental analysis, model independent analysis, was utilized, and various pharmacokinetic parameters (C max, T max, and AUC 0-t) were calculated individually for each treatment group, and the values were expressed as mean ± SEM (n = 6). Plasma samples obtained from the rats were analyzed for the concentration of silymarin through a validated RP-HPLC method and on the basis of data generated from the pharmacokinetic studies. Results indicated that the bioenhancers augmented pharmacokinetic parameters and bioavailability increased 2.4-14.5-fold in all the formulations compared with the control. The current work envisages the development of an industrially viable product that can be further subjected to clinical trials and scientifically supports the development of silymarin as a contemporary therapeutic agent with enhanced bioavailability and medicinal values.

The effects of silymarin plus glutathione on the prevention of liver ischemia-reperfusion injury

Abstract Liver ischemia-reperfusion (IR) injury is a major clinical trouble encountered in clinical practice. This study aimed to examine the therapeutic effects of silymarin (SM) plus glutathione (GSH) on hepatic IR injury using a rat model of liver IR. Fifty male rats were randomly divided into five groups, each consisting of 10 rats as follows: Sham, IR, SM-IR, GSH-IR and SM plus GSH-IR. All groups except sham were subjected to 30-min ischemia and 24-h reperfusion. The treated groups received 100 mg/kg of SM, GSH and a mixture of SM plus GSH, 60 min prior to the IR. After a period of 24 h, blood and liver samples were collected for biochemical and histopathological evaluations. Pretreatment with SM, GSH and SM plus GSH before hepatic IR significantly decreased IR-induced elevations of aminotransferases, and significantly reduced the histopathological damage scores of the liver in the late phase of IR injury. Moreover, SM plus GSH treatment prior to liver IR significantly suppressed inflammatory process and oxidative stress as demonstrated by attenuations in tumor necrosis factor-α, myeloperoxidase and the thiobarbituric acid-reactive substances. These findings suggest that administration of SM plus GSH prior to liver IR may protect the liver parenchyma from the effects of an IR injury

A network pharmacology approach to assess Reno-protective and -curative effects of methanolic extract of Malva neglecta Wallr in gentamicin induced renal toxicity rat model

Abstract The aim of present study was to explore protective and curative effects of Malve neglecta on kidneys. In silco study with network pharmacology was performed to find out potential target organs, genes and cellular cell lines which confirmed kidneys as target organ of phyto-constituents present in Malva neglecta extract. Gentamicin (40 mg/kg, i.p) was given to induce renal toxicity. Prophylactic study was performed with 300-, 600- and 900 mg/kg doses to find out nephro-protective and -curative effects and curative potential was evaluated at 900 mg/kg dose. Renal function biomarkers, blood urea, BUN, serum creatinine and uric acid, and oxidative stress measuring biomarkers, SOD, CAT, GSH and MDA levels in kidney homogenate were quantified at the end of study. Treatment groups showed decrease in blood urea, BUN, serum creatinine and uric acid levels dose dependently and curative group also showed decline in these biomarkers. SOD, CAT, GSH levels were increased and MDA level decreased in treatment groups significantly as compared to toxic control which revealed the role of oxidative stress in renal damage and anti-oxidant power of MN. Data suggested that use of MN along with drugs causing renal toxicity may prove beneficial due to its nephro- protective and curative effects.

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.

A novel supplement with yeast β-glucan, prebiotic, minerals and Silybum marianum synergistically modulates metabolic and inflammatory pathways and improves steatosis in obese mice / 中西医结合学报

OBJECTIVE@#To 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.@*METHODS@#After 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.@*RESULTS@#After 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.@*CONCLUSION@#We 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.

The potent effect of silymarin combination with Praziquantel or mirazid for Schistosoma mansoni treatment in infected male swiss albino mice

@#This work was carried out to investigate the effect of silymarin combination in the therapeutic plane of schistosomiasis with praziquantel or mirazid to enhance the liver and reduce fibrosis. Mice were divided into 2 main groups, the 1st uninfected group served as control and the 2nd group infected subcutaneously with 60 cercaria of S. mansoni per each. The infected group was subdivided into 5 subgroups, the 1st kept untreated, the 2nd and 3rd treated at the 7th week of infection with (600 mg/kg) of PZQ orally for 3 consecutive days, while the 3rd treated also orally with (150 mg/kg) of silymarin daily for 11 weeks. The 4th and 5th groups treated orally at the 7th week of infection with 600 mg/kg of MZ for 3 consecutive days, while the 5th group treated orally also with 150 mg/kg of silymarin daily for 11weeks. IgG determination showed high level in the untreated infected group. Furthermore, the infected groups treated with PZQ and PZQ with silymarin displayed the lower levels than treated with MZ. Additionally, the untreated infected group showed severe pathological changes as hyaline degeneration, inflammation, presence of worm burdens in dilated portal veins, granulomas as well as depositions of collagenous and reticular fibers indicated intense fibrosis. Treatment with PZQ alone resulted in reduction of pathological signs and decreasing of granulomas. Combination with silymarin to PZQ therapy revealed more improvement for liver besides to lowering of granulomas areas and volumes and decreasing of fibrosis. Whereas, treatment with MZ was less effective than PZQ to reduce granulomas areas, volumes and fibrosis. Although, combination of silymarin to MZ treatment resulted in more curative signs and reduction of granulomas areas, volumes and fibrosis. Furthermore, the present study concluded that PZQ still the more effective drug of schistosomiasis treatment than MZ. The silymarin is very useful in schistosomiasis treatment when combined with PZQ or MZ due to its anti-fibrotic effect.

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.

Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Abstract Background Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses.

Antioxidant And Hepatoprotective Effect Of Quercus Ilex Leaves Extract In Ethanol Induced Liver Damage In Wistar Rats

Objective: This study was undertaken to investigate the hepatoprotective and antioxidant activity of Quercus ilex leaves extract (QILE) on ethanol-induced toxicity in Wistar rats. Methods: Hepatotoxicity was induced by administering ethanol (40%) at a dose of 7.9 gm/kg/day; p. o. (1:1 of ethanol in olive oil) for 28 d. Silymarin 100 mg/kg/day; p. o. was used as a standard drug. The whole study was divided into a prophylactic and curative study. In the prophylactic study, the Silymarin and QILE (test drug) 100, 200, and 400 mg/kg Body Weight(BW) given orally one hour before administration of 40% ethanol administration for 28 d. In the curative study, 7 d of treatment of Silymarin and QILE 200 and 400 mg/kg BW was given orally after 28 d of ethanol administration to different groups. Results: Hepatoprotectivity was confirmed by the highly significantly (p<0.001) restoration of elevated biochemical parameters like SGPT, SGOT, ALP, TB, and highly significantly (p<0.001) depleted Albumin and Total protein levels by 200 mg/kg BW QILE in comparison to the positive control group. QILE 200 mg/kg highly significantly (p<0.001) raised the antioxidants by draining the elevated oxidative stress markers in comparison of positive control group. At dose levels QILE 200 mg/kg, significant (p<0.05) protection from loss in body weight and in liver weight was found when the comparison was done with the positive control group. Histopathology revealed that QILE 200 mg/kg reduced the markers of cell necrosis. Conclusion: Present study revealed that Quercus ilex leaves have antioxidant and hepatoprotective activity due to its chemical constituents.

Effects of silymarin on liver injury and bone metabolism induced by carbon tetrachloride in mice / 中国组织工程研究

BACKGROUND: Studies have found that silymarin has a regulatory role in multiple genes, which contributes to bone remodeling and prevents bone loss. In a mouse model of fracture healing, silymarin supplementation can improve tibia healing by increasing bone mineral density and serum alkaline phosphatase and osteocalcin levels. OBJECTIVE: To study the effect of silymarin on liver injury and bone metabolism induced by carbon tetrachloride in mice. METHODS: Twenty-four common Kunming mice, 10 weeks old, half male and half female, were randomly divided into three groups according to body mass. In the control group, subcutaneous injection of peanut oil 10 μL/g (double first dose) was given once every 5 days, followed by intragastric administration of 10 mL/kg/d distilled water. In the model group, animal models were made by subcutaneous injection of 40% carbon tetrachloride, followed by the same treatments as described in the control group. In the silymarin group, intragastric administration of silymarin solution 50 mg/kg/d was given after modeling. Treatments in each group lasted for 4 weeks. Each mouse was weighed every other week and was fasted for 12 hours the night before the final treatment. Under anesthesia, the mouse eyeballs were taken and blood sample from each mouse was taken to determine the serum aspartate aminotransferase and alanine aminotransferase activity; the liver was taken to measure the levels of malondialdehyde, glutathione peroxidase and superoxide dismutase in the liver homogenate; the right femur was taken to measure the bone calcium content; and the right tibia was taken for Micro CT detection to detect the changes in bone structure parameters. An approval by the Animal Ethics Committee of Guangdong Medical University was obtained with an approval No. PJ2013011. RESULTS AND CONCLUSION: Compared with the control group, the activity of aspartate aminotransferase and alanine aminotransferase in the model group was significantly increased (P < 0.05), glutathione peroxidase activity was significantly reduced (P < 0.05), bone calcium and tibial bone volume fraction, bone mineral density, and connection density were significantly reduced (P < 0.05), structural model index and anisotropy degree were significantly increased (P < 0.05), and significant liver damage and decreased bone mass and bone microstructure damage were observed. Compared with the model group, silymarin significantly reduced the activity of alanine aminotransferase (P < 0.05), and also significantly reduced the structural model index and the degree of anisotropy (P < 0.05), making the trabecular bone structure and trend more consistent. There was a clear network structure, and the bone microstructure remained intact. After the administration of carbon tetrachloride, the mice suffered liver damage with decreased bone mass and damaged bone microstructure, and silymarin administration had a certain preventive effect on liver damage and bone loss caused by carbon tetrachloride in mice.

Preparation of silymarin nanosuspension with glycyrrhizic acid as stabilizer and study of its stabilization mechanism / 中草药

Objective: To prepare silymarin nanosuspension (SM-NS) with glycyrrhizic acid as stabilizer, and investigate the in vitro release characteristics and charge stabilization mechanism. Methods: SM-NS was prepared by high-speed shear-high pressure homogenization method. SM-NS lyophilized powder were prepared by freeze-drying method and characterized by physical and chemical characterization and in vitro release. The stability mechanism of SM-NS was studied from the ionic strength and pH value. Results: The dosage of glycyrrhizic acid (GA) was 0.15%. The preparation process was shear rate of 19 000 r/min, shear time of 4 min, homogenization pressure of 100 MPa, homogenization times of 12 times, and lyoprotectant was mannitol 3%, the average particle size of SM-NS lyophilized powder was (516.4 ± 10.4) nm, PDI was (0.260 ± 0.046); The in vitro release results showed that the dissolution rate and solubility of SM-NS lyophilized powder were significantly higher than the physical mixture; The study of charge stability mechanism showed that licorice acid can provide good charge stabilization and strong resistance to environmental impact. Conclusion: SM-NS is a potential and new nano-drug with high safety, which is formed by the charge stability of GA to significantly improve the solubility and stability of silymarin.

Comparative Evaluation Of The Hepatoprotective Effect Of Costus Pictus D Don Methanolic Leaf Extract And Silymarin On Paracetamol Induced Liver Damage In Albino Wistar Rats

Background: NSAIDs are the common group of drugs used in self-medication, and this is true for especiallyParacetamol (acetaminophen).Although considered safe at therapeutic doses, in overdose, paracetamol causescentrilobular hepatic necrosis which can be fatal. As no data is available on the hepatoprotective effect ofCostus pictus D Don, we have made an attempt to investigate the protective effect of Costus pictus D Don leafextract on paracetamol induced liver damage in rats. The aim of the study is to compare the hepatoprotectiveeffect of methanolic leaf extract of Costus pictus D Don and silymarin on liver damage induced by paracetamolin Wistar rats.Materials and Methods: 30 Healthy male adult Wistar rats (16 weeks old) weighing > 250g were used for thestudy. The animals were maintained in a standard cage under controlled temperature (25+2 °C) and light (12:12light-dark cycle) in MGMC & RI central animal house. The animals were fed with standard rat pellet and hygienicwater ad libitum. 30 adult Wistar rats were randomized into 5 groups with 6 rats each as (Normal control -0.5%carboxymethylcellulose (7 days), Toxic control- 0.5% (7 days)+paracetamol 2g/kg(5th day), Test group I-200 mg/kg methanolic leaf extract+paracetamol 2g/kg(5th day) , Test group II-100 mg/kg methanolic leafextract+paracetamol 2g/kg(5th day) & Standard group - silymarin 25mg/kg (7 days) + Paracetamol 2 g/kg (5th day)The animals were sacrificed on 8th day using sodium pentobarbitone 150mg/kg i.p. serum was sent for biochemicalanalysis for liver function test. Liver was harvested and a portion was taken for histological examination.Results: In our study methanolic leaf extract of Costus pictus D Don showed beneficial effect on paracetamolinduced liver toxicity which was evident by the significant improvement in liver function test consisting of AST,ALT and ALP in a dose dependent manner which is in consistent with the histological findings.Conclusions: The study has proved the methanolic leaf extract of Costus pictus D Don posses a significanthepatoprotective activity which was comparable to the standard drug silymarin

Effect of Black Raisins (Vitis vinifera) on Aluminum Chloride Induced Alzheimer's Disease in Male Albino Rat

Alzheimer's disease (AD) is one of the most common dementia causes especially in elders. Black raisins (Vitis vinifera) have memoryenhancing effects. This study was designed to investigate the effect of oral administration of black raisins (V. vinifera) on aluminumchloride (AlCl3) induced AD in male albino rats. Forty adult male Albino rats were equally and randomly divided into five groups, 8 rats ineach. The rats of the first group received a vehicle and served as controls. The animals of the second group received raisin (5 g per rat/day)orally for 8 weeks. The rats in the third group were treated with AlCl3 (model of AD) (100 mg/kg BW/day) for 8 weeks. The animals of thefourth group were treated with AlCl3 (100 mg/kg BW/day) and raisin. The animals of the fifth group received rivastigmine (0.3 mg/kgBW/day) and AlCl3 (100 mg/kg BW/day) orally for 8 weeks. After eight weeks, the behavioral test (maze learning test) was performed on allrats to assess learning and memory. Moreover, acetylcholinesterase (AchE) activity, some neurotransmitter levels [dopamine (DA),norepinephrine (NE), gamma-aminobutyric acid (GABA)], and oxidative stress [reduced glutathione (GSH), superoxide dismutase (SOD),oxidase glutathione (GSSG), and lipid peroxidation (LPO)] were estimated in the cortex and hippocampus homogenate. Thehistopathological studies were also made in the hippocampus area. The results showed that aluminum exposure significantly decreased thelearning and memory in the maze-learning test as revealed by increase in elapsed time and error number in the maze. Significant increaseof cortex and hippocampus homogenate levels of AchE and LPO, but a significant decrease in DA, NE, GABA, GSH, GSSG, and SOD wereobserved in rats subjected to AlCl3. Histopathological evaluations of hippocampus sections of rats treated with AlCl3 showed severealterations including the increase of degenerated cells with structural damage. The treatment of rats with raisin or rivastigmine for 8 weeksshowed a pronounced attenuation on the damage caused by AlCl3 associated with the improvement of behavioral, biochemical, andhistopathological alterations. This study suggested that chronic oral administration of black raisin had neuroprotective effects andimproved learning and memory in AD animal models. These actions were done due to the antioxidant constituents of raisin.

Screening of liver protective effect of ethanolic leaf extract of Callicarpa lanata (EECL) in ethanol induced hepatotoxicity in wister rats

Background: The ethanolic extract of Callicarpa lanata (EECL), belonging to the family Verbenaceae, were studied for hepatoprotective activity in Wister rats with liver damage induced by ethanol.Methods: Ethanol treated rats showed significant increase in the levels of serum enzyme activities, total bilirubin and reduction in total proteins reflecting the liver injury caused by ethanol. EECL, at a dose of 400 and 200mg/kg body weight exhibited hepatoprotective effect by lowering the Serum Glutamate Pyruvate Transaminase (SGPT), Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Alkaline Phosphate (SALP), Gama Glutamyl Transpeptidase (GGTP), total Bilirubin to a significant extent and also significantly increased the levels of total protein in a dose dependent manner.Results: The results were highly significant at dose level of 400mg/kg body weight (p <0.01) and significant at dose level of 200mg/kg body weight (p <0.05). The effects of EECL at both levels were comparable with standard drug silymarin. The hepatoprotective activity was also supported by histopathological studies of liver tissue.Conclusions: In-vivo hepatoprotective activity of ethanolic leaf extract of Callicarpa lanata (EECL) against Ethanol induced acute liver injury in rats showed significant results in a dose dependent manner.

Assessment of The Potential Role of Parsley (Petroselinum Crispum) Leaves Extract in Ameliorating Cyclosporin A- Induced Nephrotoxicity in Rats

In this study, a potentiometric titration method by Calvin-Bjerrum and Irwing-Rosotti was used to investigate binarycomplexes of ibandronate sodium, a nitrogen-containing bisphosphonate, with Ca(II), Mg(II) and Sr(II). Dissociationconstants (pKa) of ibandronate sodium were measured and the stability constants of the complexes formed in aqueoussolutions at 22 oC (I = 0.11 M NaClO4) were determined. The stoichiometry of ibandronate sodium/metal complexes wasfound as 1/1 for each metal ion.