Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats

Abstract

Context: Different parts of the walnut [Juglans regia L. (Juglandaceae)] have been used in folk medicine for protection against liver injury, although its actual efficacy remains uncertain.

Objective: The present study investigated the protective effect of walnut leaf extract against carbon tetrachloride (CCl₄)-induced liver damage in rats.

Materials and methods: The rats were randomly divided into seven groups: control, CCl₄ (i.p., 0.5?mL/kg b.w., 50% CCl₄ in olive oil), walnut extract (at dose level of 0.2?g/kg b.w.) alone, walnut extract (at dose levels of 0.05, 0.1, 0.2 and 0.4?g/kg b.w.) with CCl₄, and treatment was carried out accordingly. On the 28th day, rats were sacrificed and blood was withdrawn by cardiac puncture. Liver damage was assessed by serum biochemical parameters (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and albumin), antioxidant enzymes (superoxide dismutase and catalase) and histopathological observation.

Results: Administration of walnut leaf extract (ranging from 0.2 to 0.4?g/kg b.w.) significantly lowered serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in CCl₄-treated rats. Walnut leaf extract increased antioxidant enzymes, including superoxide dismutase and catalase. Histopathological examination of livers showed that walnut leaves extract reduced fatty degeneration, cytoplasmic vacuolization and necrosis in CCl₄-treated rats.

Discussion and conclusion: These results suggest that walnut extract has a protective effect over CCl₄-induced oxidative damage in rat liver. These results demonstrate that walnut extract acts as a good hepatoprotective and antioxidant agent in attenuating hepatocellular damage.     

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats

Abstract

Context: Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties.

Objective: This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl₄-induced liver damage.

Materials and methods: The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200?mg/kg, p.o.) for 7?d prior to the induction of liver damage by CCl₄. Animals were then sacrificed 24?h after CCl₄ administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses.

Results: CCl₄-induced hepatotoxicity was confirmed by an increase (p?<?0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl₄-induced hepatotoxicity was also manifested by an increase (p?<?0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200?mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01?±?13.21), serum ALT (82.15?±?5.01), serum ALP (504.75?±?19.72), hepatic LPO (3.38?±?0.33), and increased levels of hepatic glutathione (0.34?±?0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl₄-intoxicated rats.

Discussion and conclusion: The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl₄-induced liver toxicity; hence, it can be used as a hepatoprotective agent.     

Hepatoprotective and antioxidant activity of Melaleuca styphelioides on carbon tetrachloride-induced hepatotoxicity in mice

Context: Liver disease is a serious problem. Polyphenolic compounds have marked antioxidant effect and can prevent the liver damage caused by free radicals. In vitro studies have revealed the strong antioxidant activity of an ellagitannin-rich plant, namely, Melaleuca styphelioides Sm. (Myrtaceae).

Objective: In view of the limited therapeutic options available for the treatment of liver diseases, the hepatoprotective potential of the methanol extract of M. styphelioides leaves (MSE) was investigated against CCl₄-induced liver injury in mice.

Materials and methods: MSE was administered (500 and 1000?mg/kg/d p.o.) along with CCl₄ for 6 weeks. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. Glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. The bioactive components of MSE were identified by NMR, UV and HRESI-MS/MS data.

Results: MSE treatment (500 and 1000?mg/kg/d) markedly inhibited the CCl₄-induced increase in the levels of AST (31 and 38%), ALT (29 and 32%), ALP (13 and 19%), and MDA (22 and 37%) at the tested doses, respectively. MSE treatment markedly increased the levels of GSH (29 and 57%) and antioxidant enzymes compared with the CCl₄-treated group. MSE was more effective than silymarin in restoring the liver architecture and reducing the fatty changes, central vein congestion, Kupffer cell hyperplasia, inflammatory infiltration, and necrosis induced by CCl₄. The LD₅₀ of MSE was more than 5000?mg/kg.

Conclusion: MSE confers potent antioxidant and hepatoprotective effects against CCl₄-induced toxicity.     

Hepatoprotective activity of Stereospermum suaveolens against CCl4-induced liver damage in albino rats

The present study aims to evaluate the hepatoprotective activity of Stereospermum suaveolens DC (Bignoniaceae). Hepatoprotective activity is studied by carbon tetrachloride (CCl₄)-induced liver damage in albino rats. The degree of protection in this activity has been measured by using biochemical parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, LDL-cholesterol and SOD, CAT, GSH, total thiols, NO, and lipid peroxidation in liver tissue homogenate. The results suggest that the methanol stem bark extract of Stereospermum suaveolens at the doses 125, 250, and 500?mg/kg and reference standard Liv-52 treated group produced significant (p <0.001) hepatoprotection against CCl₄-induced liver damage by decreasing the activities of serum enzymes, bilirubin and lipid peroxidation. The extract significantly (p <0.001) increased levels of SOD, CAT, GSH and total thiols, as compared to control group. Histopathological studies further substantiate the protective effect of the extract. It was concluded that methanol stem bark extract of Stereospermum suaveolens showed effective hepatoprotective activity.     

Hepatoprotective effect of Stachys pilifera ethanol extract in carbon tetrachloride-induce hepatotoxicity in rats

Context: Stachys pilifera Benth (Lamiaceae) has long been used to treat infectious diseases, respiratory and rheumatoid disorders in Iranian folk medicine. Antitumor and antioxidant activity of the plant have been reported.

Objective: The study was designed to assess the hepatoprotective activity of ethanol extract of Stachys pilifera in carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats.

Materials and methods: The rats were randomly divided into six equal groups (n?=?7). Group I was treated with normal saline; Group II received CCl₄ (1?mL/kg. i.p., twice a week) for 60 consecutive days; Groups III, IV and V were given CCl₄ plus Stachys pilifera (100, 200 and 400?mg/kg/d,p.o.); Group VI received the extract (400?mg/kg/d, p.o.). Histopathological analysis and measurement of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), total protein (TP) and albumin (ALB) were performed.

Results: CCl₄ caused a significant increase in the serum levels of AST, ALT, ALP and MDA as well as decreased ALB, and TP serum levels (p?4-elevated levels of ALT, AST, ALP and MDA (p?4 group (p4.

Discussion: The results revealed that the Stachys pilifera extract could provide considerable protection against CCl₄ hepatotoxicity in rats that may be related to its antioxidant properties.     

Hepatoprotective effect of cold-pressed Syzygium aromaticum oil against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats

Contexts: Exposure to environmental pollutants such as carbon tetrachloride (CCl₄) causes liver injuries. There are claims that extracts from Syzygium aromaticum (Linn.) Merrill & L.M.Perry, (Myrtaceae) protects from such injuries.

Objective: This study investigates the protective effects of cold-pressed S. aromaticum oil (CO) against CCl₄-induced liver toxicity in rats.

Materials and methods: CO was orally administered to rats in two doses (100 and 200?mg/kg) along with CCl₄ (1 mL/kg in olive oil) for 8 weeks. Indices of liver and kidney functions, lipid profile, and peroxidation were evaluated in rats’ serum and tissues. Fatty acids and bioactive lipids of CO were analyzed.

Results: High levels of monounsaturated fatty acids (39.7%) and polyunsaturated fatty acids (42.1%) were detected in CO. The oil contained high amounts of tocols and phenolics. The LD₅₀ value at 24 h was approximately 5950?mg/kg. Treatment with 200?mg/kg CO resulted in a decrease of creatinine, urea, and uric acid levels to 0.86, 32.6, and 2.99?mg/dL, respectively. Levels of TL, TC, TAG, LDL-C, and VLDL-C were decreased to 167, 195.3, 584.5, 74.6, and 39.0?mg/L, respectively, after 8 weeks of treatment. Hepatic malondialdehyde levels were reduced and glutathione levels were elevated in CO-treated rats. CO reduced the activities of AST, ALT, and ALP as well as kidney function markers, protein, and lipid profiles, respectively. Histopathological examination of liver indicated that CO treatment reduced fatty degenerations, cytoplasmic vacuolization, and necrosis.

Conclusion: CO possessed a protective effect against CCl₄-induced hepatotoxicity in rats, mediated possibly by the antioxidant properties of the oil.     

Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice

Abstract

Context: The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China.

Objective: The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl₄-induced acute liver damage in mice.

Materials and methods: Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken.

Results: Compared with the model group, administration of 400?mg/kg BELE for 7?d in mice significantly decreased the serum ALT (56.25?U/L), AST (297.67?U/L), ALP (188.20?U/L), and TBIL (17.90?mol/L), along with the elevation of TP (64.67?g/L). In addition, BELE (100, 200, and 400?mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67?U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33?nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl₄-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation.

Discussion and conclusion: The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl₄, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.     

Flavonoid constituents of Dobera glabra leaves: amelioration impact against CCl4-induced changes in the genetic materials in male rats

Context: Dobera glabra (Forssk.) Poir (Salvadoraceae) is a highly valued tree with diverse importance as special mineral sourced feed and a folkloric tool for forecasting droughts. However, there are no reports on its phytochemical and biological investigations.

Objective: Phytochemical investigation of D. glabra leaves and its protective potential against CCl₄ inducing changes in the genetic materials.

Materials and methods: D. glabra extract, DGE (70% MeOH/H₂O), was applied to polyamide column chromatography, eluting with MeOH/H₂O of decreasing polarities, followed by preparative chromatographic tools, yielded seven compounds. Three DGE doses (50, 100 and 200?mg/kg bw/d) were administrated for 8 weeks intragastrically to male albino rats prior treated with CCl₄ (0.5?mL/kg/bw). The reactive oxygen species (ROS) levels, expression changes of glutamate transporters (GLAST, GLT-1 and SNAT3) mRNA, DNA fragmentation and glutathione peroxidase (GPx) activity were investigated in the liver tissues of these rats.

Results: Isorhamnetin-3-O-β-glucopyranoside-7-O-α-rhamnopyranoside, isorhamnetin-3-O-α-rhamnopyranoside-7-O-β-glucopyranoside, kaempferol-3,7-di-O-α-rhamnopyranoside, isorhamnetin-3-O-β-glucopyranoside, kaempferol-3-O-β-glucopyranoside, isorhamnetin and kaempferol were identified. DGE (200?mg/kg bw)?+?CCl₄ exhibited the most significant reduction in ROS levels and DNA fragmentation with 251.3% and141% compared to 523.1% and 273.2% for CCl₄, respectively. Additionally, it increased significantly the mRNA expression of GLAST, GLT-1 and SNAT3 to 2.16-, 1.72- and 2.09-fold, respectively. Also, GPx activity was increased to 4.8?U/mg protein/min compared to CCl₄ (1.8?U/mg protein/min).

Discussion and conclusion: Flavonoid constituents, antioxidant effect and genotoxic protection activity of D. glabra were first reported. DGE may be valuable in the treatment and hindrance of hepatic oxidative stress and genotoxicity.     

Recombinant bovine pancreatic trypsin inhibitor protects the liver from carbon tetrachloride-induced chronic injury in rats

Abstract

Context: Bovine pancreatic trypsin inhibitor (BPTI) has been reported to relieve liver ischemia-reperfusion-induced injury in rats.

Objective: This study was designed to determine whether the recombinant BPTI (rBPTI) can prevent the chronic liver injury induced by CCl₄ in rats.

Materials and methods: Fifty male Wistar rats were divided into five groups. Rats were treated with 40% CCl₄ at a dose of 2?ml/kg body weight twice a week subcutaneously for 12 weeks. In the 8th week, they were administered intraperitoneally with rBPTI (80 MU/kg), BPTI (80 MU/kg) or hepatocyte growth-promoting factor (pHGF; 100?mg/kg) daily for the next 4 weeks.

Results: rBPTI significantly prevented the disruption of liver function of alanine aminotransferase (ALT; 172.7?±?18.16 versus 141.2?±?15.28, p?=?0.003), aspartate aminotransferase (AST; 225.10?±?36.54 versus 170.06?±?27.14, p?=?0.007) and hydroxyproline (Hyp; 1.14?±?0.27 versus 0.62?±?0.17, p?=?0.001). rBPTI significantly decreased the level of thiobarbituric acid reactive substances (TBARS; 1.15?±?0.16 versus 0.87?±?0.15, p?=?0.003) and increased the activities of superoxide dismutase (SOD; 6.07?±?0.95 versus 7.75?±?1.12, p?=?0.007). rBPTI reduced the production of cytokines of IL-1β and TGF-β. The hepatocyte necrosis, fibrosis, fatty degeneration and inflammatory cell infiltration were ameliorated by rBPTI administration.

Conclusion: This study demonstrated that rBPTI exerted a hepatoprotective effect on chronic liver fibrosis induced by CCl₄, which suggests that rBPTI may have the potential application for chronic liver injury induced by drugs metabolism and toxic substances.     

Assessment of the antioxidant potential of Cnidoscolous chayamansa

The current study is an effort to investigate the chemical constituents and antioxidant potential of Cnidoscolous chayamansa McVaugh (Euphorbiacea) root on carbon tetrachloride-induced liver damage. Albino rats were grouped into four: A - D. Groups A and B received 1?mL/kg BW of olive oil and 1?mL/kg body weight (BW) of carbon tetrachloride (CCl₄), respectively, for 8 days while those in C and D received 1?mL/ kg BW each of CCl₄ and 500 and 1000?mg/kg BW of aqueous extract of C. chayamansa root, respectively, for the same period. Chemical analysis of the plant root revealed the presence of tannins, phenolics, flavonoids, saponins, Fe, Zn, Mg, Ca, vitamins A and C. Administration of CCl₄ resulted in significant increase (P?<0.05) in liver malondialdehyde concentration while the activities of liver alkaline phosphatase, superoxide dismutase, glutathione peroxidase and catalase were significantly reduced (P?<0.05). Simultaneous administration of CCl₄ and the plant extract at 500 and 1000?mg/kg BW produced values of these biochemical parameters that compared favourably with the control (P?>0.05) in addition to increasing superoxide dismutase activity in the liver (P?<0.05). We conclude that aqueous extract of C. chayamansa root possessed antioxidant activity and protected the hepatocyte against CCl₄-induced damage. The antioxidant activity of the plant may be due to its chemical constituents.     

The novel role of β-aescin in attenuating CCl4-induced hepatotoxicity in rats

Context: β-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties.

Objective: The present study investigated the hepatoprotective effect and underlying mechanisms of β-aescin in CCl₄-induced liver damage.

Materials and methods: Thirty-five Wistar rats were divided into six groups: normal control, CCl₄ control, silymarin (50?mg/kg, p.o) and β-aescin (0.9, 1.8 and 3.6?mg/kg, i.p.) treatment for 14 d. CCl₄ (1?mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-β1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out.

Results: β-Aescin (3.6?mg/kg) markedly decreased CCl₄-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259?IU/L, respectively), total bilirubin (0.41 versus 1.35?mg/dL), TBARS (2.0 versus 8.83?nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15?μg/mL) and increased CCl₄-induced decreased GSH levels (0.095 versus 0.048?μmol/mg protein). β-Aescin (3.6?mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83?nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15?μg/mL), TGF-β1 (92.28 versus 152.1?pg/mL), collagen content (110.75 versus 301.74?μmol/100?mg tissue) and TNF-α (92.82 versus 170.56?pg/mL) when compared with CCl₄ control.

Discussion and conclusion: The findings suggest that β-aescin has a protective effect on CCl₄-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.     

Protective Effect of Aucuba Japonica Against Carbon Tetrachloride-Induced Liver Damage in Rats

ABSTRACT

Pretreatment of rats with ethanol extract from leaves of Aucuba japonica (600 mg/kg/day, po) for two days protected against CCl₄-induced depression in plasma disappearance and biliary excretion of injected sulfobromophthalein (BSP) determined 24 hr after the CCI₄ challenge (0.5 ml/kg, ip). Percent recovery of BSP in bile in 60 min for control, CCI₄, extract + CCI₄ treated rats was 66.8 ± 1.9, 56.2 ± 1.4, and 68.9 ± 2.2, respectively. Pretreatment of the extract also protected CCl₄-induced increased serum glutamic-pyruvic transaminase activity and liver necrosis as demonstrated by histological evaluations. However, pretreatment of the extract did not modify the intensity of CCl₄-induced lipid peroxidation process or cytochrome P-450 destruction. The results suggest that ethanol extract of Aucuba japonica protects CCI₄ hepatotoxicity at a site in the chain events leading to necrosis but not the activation step of CCI₄ to-CC13 and CI free radicals.     

Salvia miltiorrhiza compounds protect the liver from acute injury by regulation of p38 and NFκB signaling in Kupffer cells

Context: Salvia miltiorrhiza Bunge is a traditional Asian medicine used to treat cerebral and cardiac ischemia. However, the effects of the active compounds of S. miltiorrhiza on liver damage are unclear.

Objective: In this study, we tested the effects on acute liver injury of crude S. miltiorrhiza extracts from roots as well as neotanshinone B, dehydromiltirone, tanshinol A, tanshinone I, dihydrotanshinono I, neotanshinone A, cryptanshinono, tanshinone II A, and salvianolie acid B from purified S. miltiorrhiza extracts.

Materials and methods: Various compounds or ethanol extract of S. miltiorrhiza (50, 100, and 200?mg/kg, p.o.) were administered to rats for five consecutive days. After acute carbon tetrachloride (CCl₄)-induced liver injury by treatment of rats with a single dose of CCl₄ (0.75?mL/kg, p.o), rat liver function was tested by measuring serum biochemical parameters. Serum cytokine concentrations were assessed by enzyme-linked immunosorbent assay (ELISA). Expression of p38 and NFκB was evaluated by western blot.

Results: All S. miltiorrhiza components showed their effects on liver function from the dose from 50 to 200?mg/kg. At the dose of 200?mg/kg, they reduced serum levels of alkaline phosphatase (ALP) by 34–77%, alanine aminotransferase (ALT) by 30–57%, aspartate aminotransferase (AST) by 43–72%, creatine total bilirubin (BIL-T) by 33–81%, albumin (ALB) by 37–67%, indicating that S. miltiorrhiza extracts protected liver from CCl₄-induced damage. Moreover, S. miltiorrhiza extracts at 200?mg/kg reduced the increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) by 25–82%, interleukin-1 (IL-1) by 42–74% and interleukin-6 (IL-6) by 67–83%, indicating an effect on alleviating liver inflammation. Furthermore, in vitro, S. miltiorrhiza extracts inhibited p38 and NFκB signaling in Kupffer cells. This effect could be a main mechanism by which S. miltiorrhiza protects against acute liver toxicity.

Discussion and conclusion: Active compounds of S. miltiorrhiza protected the liver from CCl₄-induced injury. Protection might have been due to inhibition of p38 and NFκB signaling in Kupffer cells, which subsequently reduced inflammation in the liver.     

Antioxidant and hepatoprotective effects of Solanum xanthocarpum leaf extracts against CCl4-induced liver injury in rats

Context: Solanum xanthocarpum Schard. and Wendl. (Solanaceae) has been used in traditional Indian medicines for its antioxidant, anti-inflammatory, and antiasthmatic properties.

Objective: The present study demonstrates the antioxidant and hepatoprotective effects of S. xanthocarpum. On the basis of in vitro antioxidant properties, the active fraction from column chromatography of the methanol extract of S. xanthocarpum leaves (SXAF) was chosen as the potent fraction and used for hepatoprotective studies in rats.

Materials and methods: The antioxidant activity was evaluated by 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reducing power assays. Rats were pre-treated with 100 and 200?mg/kg b.w. of SXAF for 14?d with a single dose of CCl₄ in the last day. Hepatoprotective properties were determined by serum biochemical enzymes, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), antioxidant enzymes (SOD, CAT, GSH, and GST), and histopathology studies.

Results: SXAF exhibited significant antioxidant activity in scavenging free radicals with IC₅₀ values of 11.72?µg (DPPH) and 17.99?µg (ABTS). Rats pre-treated with SXAF demonstrated significantly reduced levels of serum LDH (1.7-fold), ALP (1.6-fold), and AST (1.8-fold). Similarly, multiple dose SXAF administration at 200?mg/kg b.w. demonstrated significantly enhanced levels of SOD (1.78?±?0.13), CAT (34.63?±?1.98), GST (231.64?±?14.28), and GSH (8.23?±?0.48) in liver homogenates. Histopathological examination showed lowered liver damage in SXAF-treated groups.

Discussion and conclusion: These results demonstrate that SXAF possesses potent antioxidant properties as well as hepatoprotective effects against CCl₄-induced hepatotoxicity.     

Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats

Context: Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. Objective: The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl₄-induced liver injury in rats. Materials and methods: Male Wistar rats were pretreated with guarana powder (100, 300 and 600?mg/kg) or silymarin 100?mg/kg daily for 14 days before treatment with a single dose of CCl₄ (50% CCl₄, 1?mL/kg, intraperitoneally). Results: The treatment with CCl₄ significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl₄ increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl₄-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl₄-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. Discussion and conclusion: These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl₄-induced liver damage in rats.     

Hepatoprotective effects and HSV-1 activity of the hydroethanolic extract of Cecropia glaziovii (embaúba-vermelha) against acyclovir-resistant strain

Context: Cecropia glaziovii Snethl. (Cecropiaceae), commonly known as “embaúba-vermelha”, is widely distributed throughout Latin America and has been reported in Brazilian folk medicine to treat cough, asthma, high blood pressure and inflammation.

Objective: Investigate the hepatoprotective properties of crude hydroethanolic extract of C. glaziovii as well as its in vitro antioxidant and antiviral (HSV-1 acyclovir resistant strain) activities.

Materials and methods: The hepatoprotective effect, the antioxidant properties and antiviral activity of crude hydroethanol extract (RCE40) from C. glaziovii leaves were evaluated by carbon-tetrachloride (CCl₄)-induced hepatotoxicity, by TBARS (thiobarbituric acid reactive species) and MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assays, respectively.

Results: The RCE40 extract (20?mg/kg) inhibited lipid peroxidation on liver in post injury treatment and decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, in this protocol the RCE40 (20?mg/kg) enhanced the activity of hepatic enzymes (SOD/CAT) which are involved in combating reactive oxygen species (ROS), suggesting that it possesses the capacity to attenuate the CCl₄-induced liver damage. Moreover the RCE40 (20?mg/kg) inhibited TBARS formation induced by several different inductors of oxidative stress showing significant antioxidant activity, including physiologically relevant concentration, as low as 2 µg/mL. Concerning antiviral activity, the RCE40 was effective against herpes simplex virus type 1 replication (29R acyclovir resistant strain) with EC₅₀?=?40 µg/mL and selective index (SI)?=?50.

Discussion and conclusion: These results indicate that C. glaziovii could be a good source of antioxidant and anti-HSV-1 lead compounds.     

Protective effect and antioxidant role of sweetgum (Liquidambar orientalis) oil against carbon tetrachloride-induced hepatotoxicity and oxidative stress in rats

Context: Sweetgum oil (SO) obtained from the Liquidambar orientalis Mill (Hamamelidaceae) tree has been used in Turkish folk medicine for centuries as an antiulcerigenic. Some studies have reported the antibacterial and antioxidant activities of SO; however, its effect on hepatic and oxidative stress complications is still unexplored.

Objective: This study investigates the hepatoprotective effect and the antioxidant role of SO against carbon tetrachloride (CCl₄) toxicity.

Materials and methods: The experiment included control, CCl₄, SO, and CCl₄?+?SO treatment groups. Control and SO group rats were fed a diet without CCl₄. CCl₄ and CCl₄?+?SO treatment groups received 0.5?mL/kg CCl₄ diluted in olive oil (1:1 dilution) intraperitonally injection twice per week. The CCl₄?+?SO group also received 1000?mg/kg SO-supplemented feed for 50?d. Blood and tissue samples were used for the determination of hepatic damage serum biomarkers (HDSBs) levels, antioxidant defense system constituents (ADSCs), and malondialdehyde (MDA) contents. In addition, the liver was evaluated for histopathological changes.

Results: According to the results, the HDSBs levels of the CCl₄ group were significantly (p?<?0.05) increased compared with the control, whereas the HDSB levels of the CCl₄?+?SO group resulted in marked decreases (p?<?0.05) compared with the CCl₄ group. In addition, the results showed that SO-supplemented diet restored the CCl₄-induced MDA and ADS towards to control. Hepatoprotection of SO is further substantiated by the almost normal histologic findings in the CCl₄?+?SO group against degenerative changes in the CCl₄ group.

Discussion and conclusion: It was concluded that SO has a hepatoprotective effect and antioxidant capacity against CCl₄ toxicity.     

Protective effect of Woodfordia fruticosa flowers against acetaminophen-induced hepatic toxicity in rats

Context: The flowers of Woodfordia fruticosa Kurz. (Lythraceae) are commonly used for the treatment of several ailments which includes rheumatism, leucorrhea, menorrhagia, asthma, liver disorder, and inflammatory conditions.

Objective: To evaluate the hepatoprotective property of Woodfordia fruticosa flowers against acetaminophen-induced hepatic injury in rats.

Material and methods: Acetaminophen (3?g/kg bw)-induced hepatotoxicity study was carried out by observing the effect of methanol extract of Woodfordia fruticosa flowers (400 and 600?mg/kg, bw) on some serum marker enzymes, albumin, blood urea nitrogen levels as well as liver total protein, nonenzymetic glutathione reduced content, and enzymatic antioxidant glutathione peroxidase, with histopathological evidence.

Results and discussion: Pretreatment of rats with methanol extract of Woodfordia fruticosa flowers effectively prevented the acetaminophen-induced hepatic damage as indicated by the serum marker enzymes aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase and other biochemical parameters (albumin and blood urea nitrogen). Parallel to these changes, the methanol extract of Woodfordia fruticosa flowers also prevented acetaminophen-induced oxidative stress in the rat liver by inhibiting depletion of liver total protein and restoring the levels of nonenzymatic antioxidant glutathione reduced. The biochemical changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the methanol extract of Woodfordia fruticosa flowers.

Conclusion: The results suggested that methanol extract of Woodfordia fruticosa flowers possesses protective effect against acetaminophen-induced hepatotoxicity.     

Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats

Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis.

Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl₄)-mediated liver damage.

Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague–Dawley rats once daily for 14 consecutive days at 300, 400, and 500?mg/kg b.w. prior to CCl₄ treatment (1.0?mL/kg b.w.) on the 13th and 14th days.

Results Total phenolic content in the aqueous extract of FI leaves was 65.88?±?1.84?mg gallic acid equivalent/g. IC₅₀ value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400?μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38–74% recovery), and malondialdehyde formation (25–87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E₂). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl₄-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500?mg/kg b.w.).

Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI.     

Crataegus songarica methanolic extract accelerates enzymatic status in kidney and heart tissue damage in albino rats and its in vitro cytotoxic activity

Context: Crataegus songarica K. Koch (Rosaceae) has been used in folk medicine to treat various diseases.

Objective: This study evaluates the effect of C. songarica methanol extract on the kidney and heart tissue damage of albino rats, and to determine cytotoxic activity of various extracts of songarica on various human cancer cell lines.

Materials and methods: Rats were divided into six groups, Group I received water only; Group II received CCl₄ (1?mL/kg b wt) intraperitoneal; C. songarica extract (at doses of 100, 200 and 300?mg/kg b wt) orally for 15 days. Cytotoxic activity was determined by SRB method using MCF-7, HeLa, HepG2, SF-295, SW480 and IMR-32 cell lines.

Results: Compared with CCl₄ group, administration of C. songarica extract at the dose of 300?mg/kg b wt, significantly decreases serum creatinine (59.74%), urea (40.23%) and cholesterol (54?mg/dL), MDA (0.007?nmol/mg protein) in kidney and (0.025?nmol/mg protein) in heart tissue, along with evaluation of GSH (209.79?±?54.6), GR (111.45?±?2.84), GPx (94.01?±?14.80), GST (201.71) in kidney tissue and GSH (51.47?±?1.47), GR (45.42?±?6.69), GPx (77.19?±?10.94), GST (49.89) in heart tissue. In addition, methanol, ethanol and ethyl acetate extracts exhibited potent anticancer activity on six cancer cell lines with IC₅₀ values ranging from 28.57 to 85.106?µg/mL.

Discussion and conclusion: Crataegus songarica methanol extract has a potential antioxidant effect as it protects the kidney and heart tissue against CCl₄-induced toxicity, prevents DNA damage and showed strong anticancer activity.