Antihepatotoxic Agent Research Articles

Hepatoprotective Activity of Bryophyllum pinnatum Leaves (Boiled Extract) on Albino Wistar Rats – in vivo Study

Aim: The aim of this study is to determine the effects of boiled Bryophyllum pinnatum leaves on serum liver enzymes after the administration of alcohol-induced liver damage in Albino Wistar rats.
 Study Design: Experimental.
 Place and Duration of Study: Department of Biochemistry, University of Calabar (from June to August, 2021).
 Methodology: Fresh Bryophyllum pinnatum leaves collected were washed thoroughly with clean water and allowed to dry at room temperature for 2 hours. The leaves were boiled at 100oC to obtain a boiled extract from the fresh leaves. Alcohol and leaf extract of Bryophyllum pinnatum were administered orally for a period of one week each. The rats in group 2 and 3 were induced with sub-chronic liver damage orally using a commonly available alcoholic beverage, blended whiskey at a dose of 1.5 ml per body weight for a period of one week while the rats in group 3 were given boiled leaf extracts of Bryophyllum pinnatum for one week. At the end of the two weeks treatment period, the rats were weighed and sacrificed and their blood collected for analysis (liver function test).
 Results: The animals administered with alcohol suffered mild hepatic damage. The negative control group which was administered only alcohol, had an increase in ALT when compared to the normal control. The group treated with the extract had a decrease in ALT, AST and ALP levels when compared to the negative control. This suggests that the Bryophyllum pinnatum leaves contain pharmacologically active compounds that can reduce alcohol-induced liver damage.
 Conclusion and Recommendations: The results show minimal anti-hepatotoxic activities of Bryophyllum pinnatum leaves; the extract could be said to prevent liver damage induced by alcohol toxicity. Further study in the area of pharmacology is required in order to establish this natural product as an anti-hepatotoxic agent.

Antimicrobial and cytotoxic effect of lemon grass and ginger formulation assisted copper-oxide nanoparticles

Background: Copper nanoparticles are widely used as antioxidant, antimicrobial , anticancer, anti-inflammatory, antihepatotoxic agents. Being more biocompatible, eliminates the risk for toxicity, ginger has been shown to help reduce blood sugar levels and help regulate insulin response in people. Lemongrass tea is more effective and helps to maintain optimum levels of insulin and improve the glucose tolerance in the body and also helps in preventing the growth of some bacteria and yeast. Aim: The aim of the study is to identify the antimicrobial and cytotoxic effect of lemon grass and ginger formulation assisted copper-oxide nanoparticles Method: Anti-microbial assay is done by testing the sample with certain main microorganisms and for the Cytotoxic effect, Lethal test is done using brine shrimps. Results: Copper nanoparticles synthesized using lemon grass and ginger extract can act as a potential cytotoxic agent and antimicrobial activity. However, the antimicrobial activity of the extract varied with the different bacterial samples. The cytotoxicity of nano- materials and nanocomposites tested against brine shrimps showed minimal lethality. Copper nanoparticles are previously reported to show potent antibacterial and to show cytotoxic activities in-vivo/in-vitro and our results are in accordance with their results. Conclusion: For the first time it is concluded that lemon-grass and ginger mediated Copper nanoparticles are potent therapeutic agents to be used in biomedical applications both in-vivo/in-vitro. Biologically synthesized copper-oxide nanoparticles show exhibitory diverse therapeutic potential which gains more importance currently.

A Critical Review on the Unexplored Therapeutic Treasure of Himalayan Ayurvedic Drug Daruharidra (Berberis Aristata)

Ayurveda captured almost all herbs in its indications for therapeutics from the period of Vedas. More than 700 plants are discussed elaborately in various classics of Ayurveda of different periods. Berberis aristata DC (Berberidaceae), an Indian medicinal plant, is an Ayurvedic herb used since ancient times. It is commonly known as Daruharidra and Daruhaldi. The plant is useful as an antipyretic, antibacterial, antimicrobial, antihepatotoxic, anti-diabetic, anticancer, antioxidant, and hypolipidemic agent. Our main objective was to collect information about the active constituents and major pharmacological actions of B. aristata. The review of the literature included PubMed and Science Direct searches with ‘Berberis aristata’ and ‘Daruharidra’ as initial keywords. This review aims to highlight the ethnomedicinal and pharmacological uses of B. aristata, which will give insights into developing potentially new bioactives from the plant scaffolds. This review also highlights the phytochemicals isolated from different parts of B. aristata. Daruharidra is a rich source of chemically novel compounds, such as berberine, and needs elaborate screening strategies to dwell into the pharmacological effects at the molecular level.

EVALUATION OF DIFFERENT INSECTICIDES AGAINST VIRACHOLA ISOCRATES INFESTATION IN POMEGRANATE ORCHARDS OF GILGIT-BALTISTAN, PAKISTAN

Pomegranate (Punica granatum) is a native tree of Iran and cultivated throughout the world including Himalayan regions of Pakistan and India. Pomegranate fruit is also considered as a medicinal fruit. It can act as antioxidant, anti-tumoral or anti-hepatotoxic agents, and improve cardiovascular health. Pomegranate fruit is cultivated in Gollapor vellay, Diamer, Gilgit and Ghizer areas of Gilgit-Baltistan, Pakistan. Pomegranate fruit borer (Virachola isocrates) is the main insect pest infesting the fruit orchards in this region. Present study was designed to evaluate the infestation level of pomegranate fruit borer against different commercial insecticides available to local formers. Two commercially available insecticides chloropyrifos and cypermethrine along with neem seed oil were used against the pomegranate fruit borer. Results of the study showed that cypermthrin was recorded with maximum efficacy against V. isocrates followed by chloropyrifos. All the treatments were significantly different from each other. Neem oil was also evaluated as effective treatment to reduce infestation in pomegranate orchards. This study will be helpful in control program of pomegranate fruit borer for this region and will also be very helpful to local pomegranate growers for selection of effective insecticide for the management of pomegranate fruit borer.

Synthesis, biological evaluation and molecular dynamics studies of oxadiazine derivatives as potential anti-hepatotoxic agents

Generally, herbal medicines having remarkable popularity for treating liver ailments, but they are still unacceptable because of the deprivation of herbal drug standardization. Therefore, there is a need for promising synthetic drugs to overcome the critical liver problem. We introduce 1, 3, 4-oxadiazine ring in this study to identify better anti-hepatotoxic agents via a suitable synthetic route. These oxadiazine-based derivatives were structurally confirmed by analytical and spectral data and evaluated for their anti-hepatotoxic potential. Further, in vitro hepatotoxicity studies have been done to check the toxicity level in the synthesized compound. Compounds 5a, 5b, 5c and 9d were selected for further biological evaluation according to in vitro results. After that, CCl4-induced animal model was used to evaluate in vivo anti-hepatotoxicity activity. Compound 5a with 52.99%, 59.3%, 79.34% and 5b with 52.16%, 57.65%, 75.10% revealed to be most promising for reduction in level of SGPT, SGOT and ALKP, respectively. Moreover, it was also observed that the compound 5a with 411.01%, 53.39% and 5b with 378.63%, 48.9% level of albumin and total protein were respectively. The induced-fit docking results of the compounds 5a and 5b reveal some essential binding information and exhibited desirable ADME properties, and obeyed Lipinski's rule of five. In addition, molecular dynamics studies for 100 ns further confirm the protein-ligand complex's stability, supporting the in vitro and in vivo data, and help in establishing the SAR of synthesized compounds. Two compounds, 5a and 5 b, exhibited higher anti-hepatotoxic activity than the standard drug silymarin.

Vitis vinifera polyphenols from seedless black fruit act synergistically to suppress hepatotoxicity by targeting necroptosis and pro-fibrotic mediators

Human is subjected from his surrounding to various hepatotoxins, which aggravates his liver. Nowadays, natural polyphenols have attracted great interest in health improvement, especially liver health. The present research, therefore, assessed the hepatotherapeutic potency of the isolated polyphenols (VVF1) from seedless (pulp and skin) black Vitis vinifera (VV) against CCl4-induced hepatotoxicity in vitro and in vivo. Further, VVF1 was fractionated into resveratrol-enriched (VVF2) and phenolics-enriched (VVF3) fractions to study (in vitro) the possible synergism of their coexistence. The highest content of phenolics in VVF1 displayed in vitro synergistic antioxidant and anti-hepatotoxic activities comparing to VVF2, VVF3, and silymarin (SM, reference drug). More importantly, it exhibited multiple in vivo regulatory functions via diminishing oxidative stress and inflammation, which in turn decreased necroptosis and pro-fibrotic mediators (mixed lineage kinase domain-like protein (MLKL), collagen type I alpha 1 chain (COL1A1), and transforming growth factor (TGF)-β1). In addition to these novel findings, VVF1 had higher anti-hepatotoxic potency than that of SM in most of the studied parameters. The histopathological analysis confirmed the improving role of VVF1 in the serious hepatic damage induced by CCl4. Thus, the synergistic functions of VVF1 polyphenols could be a promising new anti-hepatotoxic agent for targeting both necroptotic and profibrotic mediators.

Evaluation of antioxidants and phytoactives in Colocasia esculenta (L.) Schott

Colocasia esculenta is a perennial plant of araceae family and possess a large corm having a very large, heart-shaped leaves that are borne on thick stalks. The juvenile leaves of this plant are rich in Vitamins C, B1, B2, Riboflavin and Niacin. The tubers contain amino acids and are rich in starch. This multipurpose perennial plant is used as a traditional medicine that acts as anti-cancer agent, anti-hepatotoxic agent, antimicrobial agent, anti-diabetic agent. This shows the necessity for the study of Colocasia esculenta. In this study, The ethanolic leaves extract of Colocasia esculenta showed the maximum antioxidant activity and phytoactives efficacy, Thus suggesting the sample to be as a potential therapeutic source of various diseases. Keywords: Colocasia esculenta, Western Ghats, antioxidant, Phytoactives, Therapeutics

Hepatoprotective activity of Erythrina × neillii leaf extract and characterization of its phytoconstituents

BackgroundNatural antioxidants and anti-inflammatory agents have the ability to restore normal balance to destructed liver cells. The genus Erythrina has attracted attention for its broad spectrum of physiological activities and its rich polyphenolic and alkaloid contents. Hypothesis/PurposeThe major phytoconstituents of Erythrina × neillii, an ornamental coral tree and a hybrid between E. herbacea and E. humeana that was not previously studied, were investigated. The hepatoprotective effect and underlying mechanisms were also assessed. Study design and methodsThe main phytoconstituents in the different fractions of the alcoholic leaf extract (dichloromethane and ethyl acetate) were identified using high resolution high-performance liquid chromatography coupled with mass spectrometry (HR-HPLC-MS-MS) based on the fragmentation pattern and molecular formula of the identified compounds and on previous literature. In addition, the hepatoprotective, anti-inflammatory and antioxidant activities of three doses of E. × neillii alcoholic leaf extract (100, 250, 500 mg/kg) were investigated in methotrexate (MTX)-intoxicated rats and were compared with those of silymarin-treated rats. Liver function parameters were obtained, and a histopathological study was performed. In addition, the anti-inflammatory mediators and the antioxidant system in the liver tissues were assessed. ResultsThe dichloromethane extract revealed an abundance of alkaloids (25), in addition to tentatively identifying flavone (1), flavanone (1) and three fatty acids. Additionally, thirty-six compounds belonging to different classes of phytoconstituents with a predominance of flavonoids (21), O/C-flavone and flavonol glycosides, followed by alkaloids (9), fatty acids (4) and (2), and phenolic glycoside were identified in the ethyl acetate extract. Compared with MTX, alcoholic leaf extract (500 mg/kg) ameliorated the MTX-induced alterations by improving several biochemical marker levels, fighting oxidative stress in serum and liver tissues, and decreasing inflammatory mediators; this finding was further confirmed by the histopathological study. ConclusionThis study reveals E. × neillii, a rich source of flavonoids and alkaloids, which could be further exploited to provide a promising and safe antihepatotoxic agent source.

Ursolic acid: A natural preventive aesculapian for environmental hepatic ailments

Hepatic diseases are a major problem of worldwide proportions, and liver damage is very common since the liver has to encounter several toxic substances during their metabolism. Pollution is also one of the major causes of hepatic dysfunctioning, high level of pollutant in blood enhances the risk for abnormal liver enzyme level. Increased industrialization has prone workers to confront the several harmful chemicals in their day-to-day life that affect liver adversely; several studies have been published in the evidence of this fact; people cannot avoid their exposure to such environmental conditions but can counter with its harmful effects. Thus, to overcome this loophole, there is a demand of such agents that has the capability to fight against such toxins and pollutants. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, has established its identity as a very potent hepatoprotective agent in recent years. It is one of the strongest natural healers that are present in several medicinal plants. Its antioxidant effect makes it a potent antihepatotoxic agent as it modulates mitogen-activated protein kinases and nuclear factor-kappa B signaling pathway. UA has anticholestatic property that enhances its effectiveness somewhere equal to or in some cases better than silymarin (a well-known potent hepatoprotective agent). In recent years, it has attracted considerable attention due to its double-edged sword effect on the liver, defined in terms of prevention and cures both.

1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats.

Introduction:Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism.Objective:To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using 1H NMR based serum metabolomics.Experimental:Fourteen male rats were randomly divided into two groups (n = 7 in each group): control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D 1H CPMG and diffusion-edited nuclear magnetic resonance (NMR) spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group.Results:The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a) increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b) decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a) decreased TCA cycle activity and enhanced fatty acid oxidation, (b) dysfunction of lipid and amino acid metabolism and (c) oxidative stress.Conclusion and Recommendations:Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new drug-formulations.

METFORMIN ATTENUATES THIOACETAMIDE INDUCED HEPATOTOXIC EFFECTS IN RATS

Thioacetamide (TAA) is a well known hepatototoxic chemical that is used to induce liver cirrhosis similar to that occurred in human. This study was performed to investigate the possible protective effect of metformin against deleterious effects induced by thioacetamide in rat livers and to find out the possible mechanisms of action. Male rats were divided into 4 groups control group, TAA group received 300mg/L in drinking water for 12 weeks, metformin group received 50mg/kg/day by gavage for 12 weeks and co- treated group that received metformin 50mg/kg/day by gavage for 12 weeks in addition to TAA in the same previously mentioned dose for the same duration of time and started from the first day of metformin. The rats were weighted and euthanized. Liver tissues and blood samples were collected for estimation of key oxidative stress markers, liver enzymes and pro-inflammatory cytokine (TNF-α). The results showed that TAA induced massive functional and structural damage of the liver. Metformin treated rats significantly attenuated TAA induced changes in both liver function and structure with reduction in rises of malondialdehyde (MDA) and superoxide dismutase (SOD) levels in liver tissue with reduction in serum levels of TNF-α. The liver weights (LW) and the liver/body weight ratios (LW/BW) in thioacetamide rats had significantly increased compared to the control rats. Metformin had significantly reduced liver weights and the liver/body weight ratios compared to thioacetamide rats. On conclusion: metformin attenuates the deleterious effects of thioacetamide on liver tissue and exhibits hepatoprotection against these effects through inhibition of peroxidation, inflammation and oxidative stress and enhanced antioxidant status in rat liver tissues suggesting the potential efficacy of metformin as an addition hepatoprotective, anti-inflammatory and anti-hepatotoxic agent in treatment of liver toxicity.

The protective effect of Capparis ovata on 6-mercaptopurine-induced hepatotoxicity and oxidative stress in rats.

Capparis ovata is a member of Capparidacaeae family has been used in phytomedicine with a lot of positive effects such as an antioxidative, antihyperlipidemic, anti-inflammatory, and antihepatotoxic agent. The aim of this study was to research the protective effect of C. ovata on 6-mercaptopurine (6-MP) induced to hepatotoxicity and oxidative stress in rats. The rats were divided into 4 groups: control, 6-MP, C. ovataovate, and 6-MP + C. ovata. A complete blood count was performed, liver function test and antioxidant enzymes levels such as superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde were measured in blood before and after a 14-day test period. White blood cell and platelet counts were lower in the 6-MP group than other 3 groups (P < 0.005). Hepatic transaminase levels were higher in 6-MP group than the 3 groups (P < 0.05). Superoxide dismutase, glutathione peroxidase, and CAT levels were lower and malondialdehyde was higher in blood samples in 6-MP group than other 3 groups (P < 0.005). In conclusion, our tests were showed that C. ovata may be useful in patients receiving 6-MP therapy to prevent hepatotoxicity and in order to maintain uninterrupted therapy possibly reducing the risk of relapse. Although additional studies ensure that Capparis does not affect 6-MP antileukemic activity. We believe these results are important contribution to the literature.

In vitro antimicrobial and modulatory activity of the natural products silymarin and silibinin.

Silymarin is a standardized extract from the dried seeds of the milk thistle (Silybum marianum L. Gaertn.) clinically used as an antihepatotoxic agent. The aim of this study was to investigate the antibacterial and antifungal activity of silymarin and its major constituent (silibinin) against different microbial strains and their modulatory effect on drugs utilized in clinical practice. Silymarin demonstrated antimicrobial activity of little significance against the bacterial strains tested, with MIC (minimum inhibitory concentration) values of 512 µg/mL. Meanwhile, silibinin showed significant activity against Escherichia coli with a MIC of 64 µg/mL. The results for the antifungal activity of silymarin and silibinin demonstrated a MIC of 1024 µg/mL for all strains. Silymarin and silibinin appear to have promising potential, showing synergistic properties when combined with antibacterial drugs, which should prompt further studies along this line.

Protective effect of the edible brown alga Ecklonia stolonifera on doxorubicin-induced hepatotoxicity in primary rat hepatocytes.

As part of our efforts to isolate anti-hepatotoxic agents from marine natural products, we screened the ability of 14 edible varieties of Korean seaweed to protect against doxorubicin-induced hepatotoxicity in primary rat hepatocytes. Among the crude extracts of two Chlorophyta (Codium fragile and Capsosiphon fulvescens), seven Phaeophyta (Undaria pinnatifida, Sargassum thunbergii, Pelvetia siliquosa, Ishige okamurae, Ecklonia cava, Ecklonia stolonifera and Eisenia bicyclis), five Rhodophyta (Chondrus ocellatus, Gelidium amansii, Gracilaria verrucosa, Symphycladia latiuscula and Porphyra tenera), and the extracts of Ecklonia stolonifera, Ecklonia cava, Eisenia bicyclis and Pelvetia siliquosa exhibited significant protective effects on doxorubicin-induced hepatotoxicity, with half maximal effective concentration (EC50) values of 2.0, 2.5, 3.0 and 15.0 μg/ml, respectively. Since Ecklonia stolonifera exhibits a significant protective potential and is frequently used as foodstuff, we isolated six phlorotannins, including phloroglucinol (1), dioxinodehydroeckol (2), eckol (3), phlorofucofuroeckol A (4), dieckol (5) and triphloroethol-A (6). Phlorotannins 2 ∼ 6 exhibited potential protective effects on doxorubicin-induced hepatotoxicity, with corresponding EC50 values of 3.4, 8.3, 4.4, 5.5 and 11.5 μg/ml, respectively. The results clearly demonstrated that the anti-hepatotoxic effects of Ecklonia stolonifera and its isolated phlorotannins are useful for further exploration and development of therapeutic modalities for treatment of hepatotoxicity.

Schisandrin B attenuates acetaminophen‐induced hepatic injury through heat‐shock protein 27 and 70 in mice

Schisandrin B is an active component isolated from Schisandra chinensis (TurcZ.) Baill. that is widely used as an antihepatotoxic agent. Schisandrin B has significant hepatoprotective effect against chemical and immunological liver injury. This study aimed to investigate the effect of Schisandrin B on the expression of 27- and 70-kDa heat-shock protein (HSP) and its role in protection against acetaminophen-induced liver injury in mice. After the mice were pretreated, Western blot and real-time quantitative polymerase chain reaction were used to detect the protein and gene expression of HSP27 and HSP70, respectively; the liver tissues were subjected to histological evaluation, and alanine aminotransferase and aspartate aminotransferase activities in the serum were measured. Oral administration of Schisandrin B increased the expression of HSP27 and HSP70 in a time- and dose-dependent manner. The inducing effect of Schisandrin B on HSP27 and HSP70 was also confirmed by real-time quantitative polymerase chain reaction. In the acetaminophen-induced liver injury mouse model, the prior oral administration of Schisandrin B (200 mg/kg) three times in 24 h markedly alleviated liver injury as indicated by the amelioration of histopathological hepatic necrosis and the reduction of alanine aminotransferase and aspartate aminotransferase activities in the serum. However, the earlier actions of Schisandrin B were all suppressed significantly by Quercetin, a known HSP inhibitor. The hepatic cytoprotective action of Schisandrin B against acetaminophen-induced liver injury is mediated, at least in part, by the induction of HSP27 and HSP70 in mice.

Hepatoprotective Effect of β-Chitosan from Gladius of Sepioteuthis lessoniana Against Carbon Tetrachloride-Induced Oxidative Stress in Wistar Rats

Chitosan has attracted much attention as a biomedical material, owing to its unique biological activities. In this study, hepatoprotective effect of β-chitosan obtained from the gladius of squid Sepioteuthis lessoniana was studied against carbon tetrachloride (CCl4)-induced oxidative stress and liver injury in rats. The rats that received β-chitosan along with the administration of CCl4 showed significantly decreased plasma and tissue alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and total cholesterol, triglyceride (TG) and free fatty acid (FFA) contents, whereas the treatment with β-chitosan alone markedly increased rat hepatic and circulatory superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) and reduced glutathione (GSH) levels and decreased the malondialdehyde level. Histopathological observations recommended the marked hepatoprotective effect of β-chitosan. The CCl4-induced alterations on circulatory and hepatic antioxidant defence system were normalised by β-chitosan, and it could be concluded that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic property. Therefore, β-chitosan could be considered as antihepatotoxic agent.

Hepatoprotection using sweet orange peel and its bioactive compound, hesperidin, for CCl4-induced liver injury in vivo

The hepatoprotective effect of water extracts of sweet orange (Citrus sinensis) peel (WESP) and its biological compound, hesperidin (HD), on oxidative stress in vivo, were investigated. HD was the major compounds among the ten compounds identified using HPLC-DAD and HPLC-MS/MS analysis. Oral administration of WESP to rats at 10 and 100mg/kgbw for 28 consecutive days before a single dose of CCl4 (2ml/kgbw) demonstrates a significant protective effect by lowering the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and by improving the histological architecture of the rat liver. WESP attenuated oxidative stress by increasing the content of hepatic glutathione (GSH), and by a dramatic increase in the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). WESP induced a significant CYP2E1 activity, which suggests that WESP may be a substrate of CYP2E1. WESP at a dose of 1.0mg/kgbw and HD at 0.1mg/kgbw did not sustain the protective effect against oxidative stress, in vivo. This study demonstrated that citrus peel protects rat liver from CCl4-induced injury by attenuating hepatic oxidative stress, which suggests that WESP can be used as a therapeutic antihepatotoxic agent for the treatment of hepatic injury.

Protective and curative effect of silymarin against chlorpyrifos-induced immunotoxicity in rats

Chlorpyrifos (CPF) is a widely used organophosphorus insecticide throughout the world inagriculture and anti-termites around homes. Silymarin is a naturally occurring substance and hasantioxidant effects. For decades, it has been used clinically in Europe for the treatment ofalcoholic liver disease and as anti-hepatotoxic agent. Therefore, the present study aimed toassess the protective and curative effect of silymarin in attenuating the CPF-inducedimmunotoxicity in rats, by measuring the level of immunoglobulin G (IgG), lymphocyteviability, neutrophil phagocytic function assay, total white blood cells count (WBC) and relativedifferential white blood cells count, as well as nitric oxide (NO) level and catalase activity. Thetreatment with CPF decreased lymphocyte viability, neutrophil phagocytic index, total whiteblood cells count, relative lymphocyte count, IgG concentration and catalase activity. On theother hand, a high level of NO was detected upon animal treatment with CPF. Interestingly,pre- and post-treatment with silymarin to CPF-treated group improved the lymphocyte viability,total white blood cells count, relative lymphocyte count, catalase activity and the NO level. Preandpost-treatment with silymarin recovered phagocytic activity of neutrophils and restored IgGlevel. In conclusion, silymarin has both protective and curative effects against CPF-inducedimmunotoxicity may be through its anti-oxidant effects.

Volatile compounds and antioxidant activity of the aromatic herb Anethum graveolens

Background/Aim Anethum graveolens L. (dill) (Apiaceae) is one of the most popular culinary herbs in the world. Dill has been cultivated since ancient times, and the use of this plant for medicinal and consumption purposes has been recorded dating back to the Greek and Egyptian civilizations. Dill is widely used to give flavor to food. The aim of this work was to assess the chemical composition of the volatile compounds in dill as well as their hepatoprotective and nephroprotective activity against free radicals generated by paracetamol. Materials and methods The chemical composition of the volatile compounds of dill was assessed by gas chromatography and gas chromatography-mass spectrometry. Four groups of rats were used (the normal control group, the A. graveolens-supplemented group, the paracetamol-intoxicated group, and the A. graveolens-protected group) for studying the effect of plant infusion on panadol (paracetamol)-induced free radicals and hepatotoxicity. Plasma total antioxidant capacity, plasma catalase, cellular glutathione peroxidase, plasma total protein, albumin, alanine amino transferase, aspartate amino transferase, alkaline phosphate, γ-glutamyl transferase, total bilirubin, and direct bilirubin levels were determined. In addition, kidney functions (plasma urea and creatinine) and histopathological and histochemical changes in the liver were investigated. Results The phytochemical results identified volatile components 7-α-hydroxy manool (24.43%), l-carvone (14.28%), limonene (13.9%), epi-α-bisabolol (6.81%), α-terpinene (5.44%), and α-phellandrene (4.63%) as the main constituents. p-Cymene (2.13%), sabinene (1.98), and α-pinene (1.43%) were determined as the minor constituents. The biochemical results showed that a mega dose of paracetamol induced the production of free radicals, which caused damage to hepatocytes and nephrocytes in rats. The aqueous extract of dill revealed high antioxidant properties and acted as an extracellular neutralizer of free radicals. Histopathological and histochemical observations showed severe damage in the liver. Supplementation with dill in paracetamol-intoxicated rats attenuated the damage to the liver. Conclusion The present study revealed that A. graveolens has antihepatotoxic properties that could minimize the deleterious effects generated by hepatotoxin paracetamol, and therefore it can be used as a potent antihepatotoxic agent.

Effects of White Radish (Raphanus sativus) Enzyme Extract on Hepatotoxicity.

Raphanus sativus (Cruciferaceae), commonly known as radish is widely available throughout the world. From antiquity it has been used in folk medicine as a natural drug against many toxicants. The present study was designed to evaluate the hepatoprotective activity of radish (Raphanus sativus) enzyme extract (REE) in vitro and in vivo test. The IC50 values of REE in human liver derived HepG2 cells was over 5,000 μg/ml in tested maximum concentration. The effect of REE to protect tacrine-induced cytotoxicity in HepG2 cells was evaluated by MTT assay. REE showed their hepatoprotective activities on tacrineinduced cytotoxicity and the EC50 value was 1,250 μg/ml. Silymarin, an antihepatotoxic agent used as a positive control exhibited 59.7% hepatoprotective activitiy at 100 μg/ml. Moreover, we tested the effect of REE on carbon tetrachloride (CCl4)-induced liver toxicity in rats. REE at dose of 50 and 100 mg/kg and silymarin at dose of 50 mg/kg were orally administered to CCl4-treated rats. The results showed that REE and silymarin significantly reduced the elevated levels of serum enzyme markers induced by CCl4. The biochemical data were supported by evaluation with liver histopathology. These findings suggest that REE, can significantly diminish hepatic damage by toxic agent such as tacrine or CCl4.