Hepatoprotective Effect Of Silymarin Research Articles

Cardioprotective and Hepatoprotective Potential of Silymarin in Paracetamol-Induced Oxidative Stress.

Silymarin, derived from Silybum marianum, has been used in traditional medicine for various ailments. In this study, the cardioprotective and hepatoprotective effects of silymarin against paracetamol-induced oxidative stress were examined in 28 male Swiss Webster mice, divided into four groups and treated for 7 days (via the oral route) with (a) saline 1 mL/kg (control group), (b) saline 1 mL/kg + single dose of paracetamol 110 mg/kg on the 7th day; (c) silymarin 50 mg/kg; and (d) silymarin 50 mg/kg + single dose of paracetamol 110 mg/kg on the 7th day. In vitro and in vivo antioxidant activity together with liver enzyme activity were evaluated. Histopathological and immunohistochemical assessment was performed. Silymarin mitigated paracetamol-induced liver injury by reducing oxidative stress markers such as lipid peroxidation and restoring antioxidant enzyme activity. Silymarin treatment resulted in a significant decrease in liver enzyme levels. Reduced necrosis and inflammatory infiltrate in liver tissues of silymarin-treated groups were detected as well. Immunohistochemical analysis demonstrated reduced expression of inflammatory markers (COX2, iNOS) and oxidative stress marker (SOD2) in the liver tissues of the silymarin-treated groups. Similar trends were observed in cardiac tissue. These results suggest that silymarin exerts potent hepatoprotective and cardioprotective effects against paracetamol-induced oxidative stress, making it a promising therapeutic agent for liver and heart diseases associated with oxidative damage.

Hepatoprotective effects of silymarin on cyclophosphamide-induced hepatotoxicity in male rats

Hepatoprotective effects of silymarin on cyclophosphamide-induced hepatotoxicity in male rats

Hepato-protective effects of Silymarin against methotrexate-induced hepatotoxicity in rat model

Hepato-protective effects of Silymarin against methotrexate-induced hepatotoxicity in rat model

Enhanced bioavailability and hepatoprotective effect of silymarin by preparing silymarin-loaded solid dispersion formulation using freeze-drying method.

This study aimed to develop a solid dispersion formulation of silymarin (Silymarin-SD) using freeze-drying method to enhance its oral bioavailability (BA) by inhibiting the intestinal first-pass effect and increasing its solubility and permeability. Silymarin-SD formulation (i.e., silymarin:tween 80:hydroxypropyl cellulose (HPC) = 1:1:3 (w/w/w) significantly increased silymarin permeability in the duodenum, jejunum, and ileum by decreasing the efflux ratio of silymarin and by inhibiting silymarin-glucuronidation activity, in which tween 80 played a crucial role. As a result, orally administered Silymarin-SD formulation increased plasma silymarin concentrations and decreased silymarin-glucuronide in rats compared with silymarin alone and silymmarin:D-α-tocopherol polyethylene glycol 1000 succinate (1:1, w/w) formulation. In addition to modulating intestinal first-pass effect, Silymarin-SD formulation showed a significantly higher cumulative dissolution for 120min compared with that of silymarin from the physical mixture (PM) of the same composition as Silymarin-SD and silymarin alone; the relative BA of silymarin-SD increased to 215% and 589% compared with silymarin-PM and silymarin alone, respectively. This could be attributed to the amorphous status of the Silymarin-SD formulation without chemical interaction with excipients, such as tween 80 and HPC. Moreover, the hepatoprotective effect of Silymarin-SD in acetaminophen-induced acute hepatotoxicity, as estimated from the alanine aminotransferase and aspartate aminotransferase values, was superior to that of silymarin. In conclusion, the increase in the dissolution rate and intestinal permeability of silymarin, and the inhibition of silymarin-glucuronidation by the Silymarin-SD formulation, prepared using tween 80 and HPC, increased its plasma concentration and resulted in a superior hepatoprotective effect compared to silymarin.

Silymarin in combination with chlorogenic acid protects against hepatotoxicity induced by doxorubicin in rats: possible role of adenosine monophosphate-activated protein kinase pathway.

Many xenobiotics are known to cause hepatic damage with subsequent significant morbidity and mortality. Doxorubicin (DOX) is a broad-spectrum antineoplastic agent. DOX is reported to cause hepatocellular damage. Previous studies verified the promising role of many natural antioxidant products against various models of hepatic dysfunction. We conducted this study to evaluate the possible hepatoprotective effect of silymarin (SILY) and/or chlorogenic acid (CGA) in a rat model of DOX-induced hepatotoxicity. For this purpose, we randomly divided 30 adult male rats into five equal groups as control, DOX, co-treated DOX with SILY, co-treated DOX with GCA and co-treated DOX with SILY and CGA groups. All treatments were administered every second day for 4 weeks. Our results showed that simultaneous SILY and CGA administration caused a significant decrease in hepatic apoptosis biomarkers (hepatic caspase-3 and nuclear factor-κB levels), a significant improvement in hepatic oxidant/antioxidant status (malondialdehyde and superoxide dismutase) and significant decrease in hepatic pro-inflammatory biomarkers (tumor necrosis factor-alpha and interlukin-1β) compared with DOX treatment. We concluded that adding CGA to SILY acts as a hepatoprotective agent against DOX-induced liver injury through inhibiting apoptosis biomarkers, maintaining antioxidant enzyme levels, decreasing pro-inflammatory cytokines as well as regulating liver adenosine monophosphate-activated protein kinase signaling.

Chronic liver disease during a pandemic: preventive support for the combined phytopreparation Fumarta

The spread of SARS‑CoV‑2 virus among humanity has identified a number of new challenges in the field of medical science. In this regard, it is very important to understand the possible involvement of the liver in the infectious process, as well as the effect of this virus on liver function in its chronic pathology. The article provides an overview of available sources of information regarding views on direct viral liver damage COVID‑19, as well as the features of the course and prognosis of this infection in patients with chronic liver disease and cirrhosis. It was emphasized that chronic liver diseases are considered as a high risk factor for COVID‑19 infection, and are also predicted to be at an increased risk for the severe course of this infection with the development of complications.Substantial support to patients with chronic liver diseases during the COVID‑19 pandemic can be provided by the Fumarta combination drug (Farmak), which includes fumarin alkaloid from the extract of dry herb of the fumaria officinalis and silymarin from the extract of dried fruit of milk thistle. This composition of the drug Fumarta allows normalizing the digestive disorders, which constantly accompany chronic liver disease. In the article, digestive disorders are considered from the point of view of biliary insufficiency, which occurs in virtually every chronic liver disease. Normalization of the formation of bile, its composition with the restoration of rheological properties, improves not only general well‑being of a patient, but also positively affects the restoration of the functional capabilities of the liver. The data on the study of each of the active components of the Fumarta drug are presented, which indicates the advisability of its use in this group of diseases.The healing properties of the Fumarta drug are stipulated by the optimal combination of the hepatoprotective effects of silymarin with the normalization of bile secretion and biliary motility by fumarin. The combination of hepatoprotective and choleretic activity complement and enhance the action of each other, which helps to optimize the functioning of the entire digestive system. Patients with liver disease in the context of the COVID‑19 pandemic are recommended to take Fumarta drug, the components of which have a versatile positive effect in chronic liver diseases as preventive support. Approaches to pharmacotherapy of chronic liver diseases among the convalescents of COVID‑19 are also being considered. In this regard, Fumarta may act as one of the optimal drugs for choosing a rehabilitation course for these patients.

Hepatoprotective effects of silymarin against diclofenac-induced liver toxicity in male rats based on biochemical parameters and histological study

Diclofenac (DIC) is a phenyl acetic acid derivative which is well known for its analgesic and anti-inflammatory. In our study, the rats were divided into four groups. Group 1, control group; Group 2 received DIC-only; Groups 3 and 4 received DIC plus silymarin. The results showed that levels of CAT, SOD, GPx and GSH significantly reduced and levels of ALT, AST, ALP, total bilirubin, nitrite content, MDA, serum TNF-α and TNF-α gene expression were significantly elevated in second group compared to control group. In other hand, treatment with silymarin resulted in a significant elevation in CAT, SOD, GPx, GSH and a significant reduction in MDA, ALT, AST, ALP, total bilirubin, nitrite content, serum TNF-α, and gene expression of TNF-α in comparison with second group. Histopathological injuries were also improved by silymarin administration. The results confirm that silymarin has a protective effect on DIC-induced liver toxicity and oxidative stress in male rats.

Hepatoprotective Effects of Silymarin on Liver Injury via Irisin Upregulation and Oxidative Stress Reduction in Rats with Type 2 Diabetes.

Diabetes is one of the most prevalent metabolic diseases. Irisin (FNDC5 protein) is involved in the new strategy of combating type 2 diabetes. In the liver, the antidiabetic mechanism of silymarin at the molecular level is unknown. This study investigated the effects of silymarin on irisin and the related gene expression and oxidative stress status in the liver of type 2 diabetic rats. Thirty-six rats were divided into 6 groups (n=6 each) by simple randomization: control, control+silymarin (60 mg/kg daily in normal saline orally for 60 days), control+silymarin (120 mg/kg daily in normal saline orally for 60 days), diabetic, diabetic+silymarin (60 mg/kg daily for 60 days), and diabetic+silymarin (120 mg/kg daily for 60 days). Biochemical parameters were measured by spectrophotometric and immunoassay methods, and quantitative polymerase chain reaction was used to evaluate gene expression. The data were analyzed by one-way ANOVA, followed by the Tukey test, using SPSS software, version 16.0. The results were considered statistically significant at a P value less than 0.05. In the diabetic rats treated with silymarin (60 and 120 mg/kg), by comparison with the diabetic group, body weight (P=0.04 and P=0.02), insulin (P<0.001), expression of PGC-1α (P=0.04 and P=0.02), expression of FNDC5 (P=0.03 and P=0.01), and concentration of irisin in the liver (P=0.02 and P=0.01) and serum (P<0.001) were significantly increased, whereas the levels of glucose (P<0.001), HOMA-IR (P=0.03 and P=0.01), and liver injury markers (P<0.001) were significantly reduced. Oxidative stress status and histopathological changes were improved in the treated groups. These results suggest that silymarin because of its ability to upregulate irisin and antioxidant effects can be considered an antidiabetic agent.

Silymarin prevents acetaminophen-induced hepatotoxicity via up-regulation of the glutathione conjugation capacity in mice

Our previous study showed that silymarin, a mixture of flavonolignans extracted from seeds of milk thistle, modulated hepatic transsulfuration reactions, leading to an increase in glutathione (GSH) synthesis. To investigate its pharmacological significance, we determined the effect of silymarin on acetaminophen (APAP)-induced liver injury. Silymarin administration to mice prevented the induction of APAP-hepatotoxicity as measured by changes in plasma enzyme activities, hepatic lipid peroxidation and formation of nitrotyrosine protein-adducts. Depletion of hepatic GSH was inhibited significantly. Plasma APAP, APAP-glucuronide or APAP-sulfate level was not changed, but APAP-GSH, APAP-cysteine and APAP-N-acetylcysteine levels were elevated. Silymarin treatment did not induce proteins or activities of Cyp2e1, Cyp1a2, and Cyp3a11, the major cytochrome P450 subtypes responsible for the metabolic activation of APAP to a reactive metabolite, N-acetyl-p-benzoquinoneimine. The results suggest that the hepatoprotective effect of silymarin is associated with an increase in the metabolic disposition of N-acetyl-p-benzoquinoneimine via up-regulation of the GSH conjugation capacity.

Micronized silymarin extract reduced hepatotoxic effect of fenofibrate in hereditary hypertriglyceridemic rats

Aim: Hypolipidemic effect of fibrates, mediated by PPARα activation, can be accompanied by liver damage due to oxidative stress and inflammation. Hepatoprotective effect of silymarin was demonstrated in clinical and experimental studies. We investigated whether silymarin improves negative effect of fenofibrate in experimental model of metabolic syndrome, hereditary hypertriglyceridemic rats (HHTg).

Hepatoprotective Effect of Silymarin and Propolis in Chemically Induced Chronic Liver Injury in Rats

According to World Health Organization (WHO), chronic liver disease is a major problem that causes significant morbidity and mortality in both western and developing countries. However, till now no ideal hepatoprotective agents are available in the modern system. This has increased the need to depend on complementary and alternative systems of medicine. Silymarin and propolis among phytochemicals that show anti-inflammatory, healing, antioxidant and several other promising properties. Our aim is to investigate protective effect of silymarin and propolis in chemically induced chronic liver injury in rats. A total of 60 male albino rats (90±10 days old) were divided equally into ten groups: (6 rats per each group). The experiment lasted along four months, through which all groups except for group 1 and 6 were given silymarin and propolis. Liver injury was induced in groups 6, 7, 8,9,10 while other groups were injected with saline and oil of the same volume as following. Group 1: served as control –ve, the rats were fed on basal ration and water ad libitum. Group 2 (silymarin 100 mg/ kg b.wt). Group 3 (propolis 100 mg/kg b.wt). Group 4 (propolis 150 mg/kg b.wt). Group 5 (propolis 200 mg/kg b.wt). Group 6 served as control +ve (DEN+CCl4). Group 7 (liver injury+ silymarin 100 mg/ kg b.wt). Group 8 (liver injury+ propolis 100 mg /kg b.wt). Group 9 (liver injury + propolis 150 mg/kg b.wt). Group 10 (liver injury + propolis 200 mg/kg b.wt). Blood samples were collected from all groups after four months and serum was separated for biochemical analysis of liver functions and tumar markers Administration of DEN+CCl4 significantly increased liver weight, liver/body weight index, AST, ALT, ALP, GGT, AFP and CEA while, body weight, total protein, albumin and A/G ratio were markedly decreased. Treatment with silymarin and propolis caused a significant reduction in serum levels of AST, ALT, ALP, GGT and tumor markers moreover, loss of body weight and liver/body weight index were successfully decreased while, total protein and albumin were increased by those natural products. The results indicate a protective effect for silymarin and propolis against hepatic injury induced by DEN+CCl4 that may be due to their ability to block the bioactivity of those hepatotoxicants and their antioxidant properties.

Hepatoprotective Effect of Silymarin (Silybum marianum) on Hepatotoxicity Induced by Acetaminophen in Spontaneously Hypertensive Rats.

This study was aimed to investigate the effect of Silymarin (SLM) on the hypertension state and the liver function changes induced by acetaminophen (APAP) in spontaneously hypertensive rat (SHR). Animals normotensive (N) or hypertensive (SHR) were treated or not with APAP (3 g/kg, oral) or previously treated with SLM. Twelve hours after APAP administration, plasmatic levels of liver function markers: alanine aminotransferase (ALT), aspartate aminotransferase (AST), glucose (GLU), gamma glutamyl transferase (γ-GT), and alkaline phosphatase (ALP) of all groups, were determined. Liver injury was assessed using histological studies. Samples of their livers were then used to determine the myeloperoxidase (MPO) activity and nitric oxide (NO) production and were also sectioned for histological analysis. No differences were observed for ALT, γ-GT, and GLU levels between SHR and normotensive rats groups. However, AST and ALP levels were increased in hypertensive animals. APAP treatment promoted an increase in ALT and AST in both SHR and N. However, only for SHR, γ-GT levels were increased. The inflammatory response evaluated by MPO activity and NO production showed that SHR was more susceptible to APAP effect, by increasing leucocyte infiltration. Silymarin treatment (Legalon) restored the hepatocyte functional and histopathological alterations induced by APAP in normotensive and hypertensive animals.

Hepatoprotective effect of silymarin on di(2-ethylhexyl)phthalate (DEHP) induced injury in liver FL83B cells

Di(2-ethylhexyl)phthalate (DEHP), is a toxic environmental pollutant in our life which can contaminate air, water, and soil. The hepatoprotective effect of silymarin on DEHP-induced injury in FL83B mouse liver cells was investigated by analyzing the cell viability, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), cell cycle arrest, and cell morphology. The results revealed that cell viability decreased while released LDH and ALT increased with the increase of DEHP concentrations. Moreover, cell population of sub-G1 and S phase increased as the concentrations of DEHP increased. Silymarin at 25μM achieved the highest hepatoprotective effect and exhibited 79% cell viability while only 46% cell viability was found in DEHP injured control. It was also found to reduce LDH release and cell populations of sub-G1 and S phase. Therefore, silymarin could ameliorate DEHP-induced injury and have potential to be further developed as a natural ingredient of health food against phthalate plasticizers induced liver injury.

Hepatoprotective Effect of Silymarin on Arthritic Rats Treated with Leflunomide

Hepatoprotective Effect of Silymarin on Arthritic Rats Treated with Leflunomide

EFFECT OF QUERCETIN ON HEPATOPROTECTIVE ACTIVITY OF SILYMARIN AGAINST THIOACETAMIDE INTOXICATED RATS

The study was designed to investigate the interactive effect of Quercetin on hepatoprotective effect of Silymarin against thi oacetamide induced hepatotoxicity in rats. Albino rats of either sex were divided int o six groups and treated for 7 days. Group 1 and 2 served as normal and toxic control and other groups were treated with Silymarin (100 mg/kg), Quercetin (100 mg/kg), high and low dose combination of Silymarin (100 and 50 mg/kg) + Quercetin (100 and 50 mg/kg) respectively. Liver damage was i nduced in by administering thioacetamide (100 mg/kg, s.c ) on 7 th day. 48 h after the administration of thioacetamide blood samples were collected by retro - orbital puncture method and levels o f alanine aminotransferase , a spartate aminotransferase , alkaline phosphatase and bilirubin in serum were evaluated. Histopathology of liver was also carried out. The combination of Silymarin (100 mg/kg) + Quercetin (100 mg/kg) demonstrated significant reduction in enzyme and bilirubin level in serum compared to Silymari n (100 mg/kg) alone treate d group which was supported by histopathological study. It can be concluded that Quercetin has got a synergistic effect on hepatoprotective acti on of Silymarin against thioacetamide induced hepatotoxicity.

Antioxidant, anti-inflammatory and hepatoprotective effects of silymarin on hepatic dysfunction induced by sodium nitrite

Sodium nitrite, a food additive that is used as a color fixative and preservative for meats and fish, has been reported to have adverse health effects due to increased oxidative stress that could be harmful to different organs including the liver. Meanwhile, silymarin protects against hepatotoxicity caused by a variety of agents, on account of its antioxidative and anti-inflammatory effects. We therefore examined the impact of dietary silymarin on sodium nitrite-induced liver damage in rats. Fifty adult male Sprague-Dawley rats received 80 mg/kg sodium nitrite in the presence or absence of silymarin (10 and 25 mg/kg). Hepatic proinflammatory cytokines (TNF-α and IL-1β), hepatic fibrosis marker (MCP-1 and TGF-β1), mitochondrial activity marker (cytochrome C oxidase) and c-reactive protein (CRP) levels were measured. Hepatic apoptosis was assessed through determination of caspase-3 activity and DNA fragmentation. We found that oral sodium nitrite enhanced oxidative stress with subsequent increases in TNF-α (2-fold), IL-1β (4-fold), MCP-1 (4-fold), TGF-β1 (3-fold) and CRP (4-fold). In addition, sodium nitrite brings about reduced cytochrome C oxidase and enhanced caspase-3 activity and DNA fragmentation. Daily treatment with silymarin markedly ameliorated all these effects. Silymarin ameliorated the impairment of hepatic function in rats that had ingested sodium nitrite. Silymarn possesses antioxidant, anti-inflammatory, antifibrotic and anti-apoptotic effects.

Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

Background and the purpose of the studySilymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated.MethodsWe genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month).ResultsA significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.ConclusionThis is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy.

Induction of Microsomal Liver Enzymes by Silymarin in Experimental Animals

Background: previous researches showed that the hepatoprotective effect of silymarin was through inhibition of cytochrome p450- system (e.g. protection against Amanita toxin), in addition to protection from free radicals generated by this enzymatic system. In contrast to that, many evidences clarified that silymarin may increase first pass metabolism of e.g. cyclosporine and benzodiazepenes.Objective: Our aim from this animal experiment was to relieve this confusion and detect that this herbal extract is absolutely hepatoprotective or induce hepatotoxicity in other conditions.Materials and Methods: this study was performed on 15 healthy male rats randomized into two treatment groups; first group (5 rats) pretreated with phenobarbital (I.P) then given acetaminophen (I.P) and the second group (5 rats) pretreated with silymarin (orally) then given acetaminophen (I.P.); while the last five rats were considered as control group for comparison . Activities of SGOT, SGPT and histopathological sections were detected for both groups and compared with that of control.Results: for both treatment groups, the activities of transaminase enzymes were significantly higher than control group. Meanwhile; activity of these enzymes and severity of hepatic damage were significantly higher for Phenobarbital group compared with silymarin.Conclusion: we can conclude from this experimental study that, even though silymarin act as hepatoprotective by multifactorial mechanisms (antioxidant, increase glutathione level, antifibrotic, anti-inflammatory and enzyme inhibitor), it may act as enhancer for some hepatotoxic agents (like acetaminophen) by cytochrome P-450 induction mechanism.

Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats

© 2011, INASL 40 Synthesis and Antihepatotoxic Activity of 5-(2,3-dihydro-1,4-benzodioxane-6-yl)-3-substitutedphenyl-4,5-dihydro-1H-pyrazole Derivatives Habibullah*,**, B Ahmed** *Department of Pharmaceutical Chemistry, Alwar Pharmacy College, Alwar, Rajasthan **Antihepatotoxic Research Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi Background and Objective: Silymarin isolated from seeds of Silybum marianum commonly known as ‘milk thistle’ has been found most potent antihepatotoxic agent against a variety of toxicants. The Silymarin has been found to be a mixture of three isomers of flavonolignan i.e., silybin, silychristin and silydianin. The silybin is the most potent component containing 1,4-dioxan ring system. Other isomer silychristin and silydianin do not possess 1,4-dioxan ring system and thus, do not display significant antihepatotoxic activity. Based on the above hypothesis we learned that 1,4-dioxane ring system plays an important role in exhibiting antihepatotoxic activity, and hence we have prepared some new pyrazoline derivatives bearing 1,4-dioxane ring system and evaluated them for antihepatotoxic activity against CCl4induced hepatotoxicity in rats. Material and Methods: The titled pyrazolines were prepared by refluxing 2,3-dihydro-1,4-benzodioxane-6-yl)-1-substituted-phenylprop2-en-1-one derivatives with hydrazine hydrate in absolute ethanol and few drops of glacial acetic acid. The synthesized compounds were evaluated for antihepatotoxic activity by measuring different biochemical parameters glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP) and total protein against CCl4-induced hepatotoxicity in Wistar albino rats as well as histopathological study of the liver. Results: The administration of silymarin (standard drug) and synthesized compounds at a dose level of 10 mg/Kg body weight, prevented CCl4-induced elevation of SGOT, SGPT, ALP, and prevented decrease in total protein. The histopathological studies also showed significant recovery of hepatocytes of the liver in the standard drug and compound-treated animals. Conflict of Interest: None Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels P Vasanth Raj, K Nitesh, P Jain, M Neena Sankhe, J Venkata Rao, C Mallikarjuna Rao, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka Background and Aims: Oxidative stress plays a pivotal role in the pathogenesis and progression of alcoholic liver disease (ALD). Considering the antihepatotoxic property of silymarin, a well known antioxidant (flavonoid); we investigated the hepatoprotective effect of silymarin and underlying mechanism(s). Methods: Twenty-four Wistar strain albino rats (180–200 g) of either sex were used. The animals were divided into three groups and treated for 60 days as follows: (1) normal control group received the vehicle (sodium CMC 0.3%); (2) ethanol group was administered ethanol 3.6 g/Kg (30%, 10 mL/Kg) 1 hour after ingestion of sodium CMC 0.3%; (3) ethanol plus silymarin group received silymarin 100 mg/Kg 1 hour prior to the administration of ethanol 3.6 g/Kg. Animals received ethanol and silymarin by oral route daily. Liver damage was evaluated by histopathology and liver function test. At molecular level, expression of P53, Bax and bcl-2 was determined by reverse transcriptase polymerase chain reaction (RT PCR). Results: Silymarin at 100 mg/Kg each ameliorated ethanol-induced macrovesicular steatosis and parenchymatous degeneration in hepatocytes, and decreased serum aminotransferases level. Ethanol downregulated antiapoptotic Bcl-2, upregulated pro apoptotic P53 and Bax mRNA levels in liver hepatocytes, thus, inducing apoptosis. However, this alteration in mRNA levels of P53, Bax and Bcl-2 was significantly prevented by silymarin treated animals at a dose of 100 mg/Kg body weight. Conclusion: Together, these results identify the biological efficacy of silymarin against ethanol-induced hepatotoxicity in rats. Hence, silymarin merits further investigation to support its molecular mechanism. Conflict of Interest: None Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats N Kumar, P Vasanth Raj, A Tiwari, A Chaudhary, C Mallikarjuna Rao, N Gopalan Kutty, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal Background and Aims: Dehydrozingerone (DZ) is a prototype constituent of ginger and has shown radioprotection through its antioxidant activity. Chemically DZ is a chalcone in nature and can be prepared easily by reactions of vanillin with acetones. Antioxidant activity 03_JCEH-Abstract.indd 40 3/18/2011 11:13:05 AM

Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels

© 2011, INASL 40 Synthesis and Antihepatotoxic Activity of 5-(2,3-dihydro-1,4-benzodioxane-6-yl)-3-substitutedphenyl-4,5-dihydro-1H-pyrazole Derivatives Habibullah*,**, B Ahmed** *Department of Pharmaceutical Chemistry, Alwar Pharmacy College, Alwar, Rajasthan **Antihepatotoxic Research Laboratory, Faculty of Pharmacy, Jamia Hamdard, New Delhi Background and Objective: Silymarin isolated from seeds of Silybum marianum commonly known as ‘milk thistle’ has been found most potent antihepatotoxic agent against a variety of toxicants. The Silymarin has been found to be a mixture of three isomers of flavonolignan i.e., silybin, silychristin and silydianin. The silybin is the most potent component containing 1,4-dioxan ring system. Other isomer silychristin and silydianin do not possess 1,4-dioxan ring system and thus, do not display significant antihepatotoxic activity. Based on the above hypothesis we learned that 1,4-dioxane ring system plays an important role in exhibiting antihepatotoxic activity, and hence we have prepared some new pyrazoline derivatives bearing 1,4-dioxane ring system and evaluated them for antihepatotoxic activity against CCl4induced hepatotoxicity in rats. Material and Methods: The titled pyrazolines were prepared by refluxing 2,3-dihydro-1,4-benzodioxane-6-yl)-1-substituted-phenylprop2-en-1-one derivatives with hydrazine hydrate in absolute ethanol and few drops of glacial acetic acid. The synthesized compounds were evaluated for antihepatotoxic activity by measuring different biochemical parameters glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), alkaline phosphatase (ALP) and total protein against CCl4-induced hepatotoxicity in Wistar albino rats as well as histopathological study of the liver. Results: The administration of silymarin (standard drug) and synthesized compounds at a dose level of 10 mg/Kg body weight, prevented CCl4-induced elevation of SGOT, SGPT, ALP, and prevented decrease in total protein. The histopathological studies also showed significant recovery of hepatocytes of the liver in the standard drug and compound-treated animals. Conflict of Interest: None Study of Silymarin on Ethanol Induced Hepatotoxicity and Expression of Bcl-2, Bax and p53 Levels P Vasanth Raj, K Nitesh, P Jain, M Neena Sankhe, J Venkata Rao, C Mallikarjuna Rao, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka Background and Aims: Oxidative stress plays a pivotal role in the pathogenesis and progression of alcoholic liver disease (ALD). Considering the antihepatotoxic property of silymarin, a well known antioxidant (flavonoid); we investigated the hepatoprotective effect of silymarin and underlying mechanism(s). Methods: Twenty-four Wistar strain albino rats (180–200 g) of either sex were used. The animals were divided into three groups and treated for 60 days as follows: (1) normal control group received the vehicle (sodium CMC 0.3%); (2) ethanol group was administered ethanol 3.6 g/Kg (30%, 10 mL/Kg) 1 hour after ingestion of sodium CMC 0.3%; (3) ethanol plus silymarin group received silymarin 100 mg/Kg 1 hour prior to the administration of ethanol 3.6 g/Kg. Animals received ethanol and silymarin by oral route daily. Liver damage was evaluated by histopathology and liver function test. At molecular level, expression of P53, Bax and bcl-2 was determined by reverse transcriptase polymerase chain reaction (RT PCR). Results: Silymarin at 100 mg/Kg each ameliorated ethanol-induced macrovesicular steatosis and parenchymatous degeneration in hepatocytes, and decreased serum aminotransferases level. Ethanol downregulated antiapoptotic Bcl-2, upregulated pro apoptotic P53 and Bax mRNA levels in liver hepatocytes, thus, inducing apoptosis. However, this alteration in mRNA levels of P53, Bax and Bcl-2 was significantly prevented by silymarin treated animals at a dose of 100 mg/Kg body weight. Conclusion: Together, these results identify the biological efficacy of silymarin against ethanol-induced hepatotoxicity in rats. Hence, silymarin merits further investigation to support its molecular mechanism. Conflict of Interest: None Hepatoprotective Action of Dehydrozingerone in Carbon Tetrachloride and Thioacetamide-induced Hepatotoxicity in Wistar Rats N Kumar, P Vasanth Raj, A Tiwari, A Chaudhary, C Mallikarjuna Rao, N Gopalan Kutty, N Udupa Manipal College of Pharmaceutical Sciences, Manipal University, Manipal Background and Aims: Dehydrozingerone (DZ) is a prototype constituent of ginger and has shown radioprotection through its antioxidant activity. Chemically DZ is a chalcone in nature and can be prepared easily by reactions of vanillin with acetones. Antioxidant activity 03_JCEH-Abstract.indd 40 3/18/2011 11:13:05 AM