Boschniakia rossica prevents the carbon tetrachloride-induced hepatotoxicity in rat

The present study was undertaken to investigate the hepatoprotective effect of Boschniakia rossica extract (BRE), rich in phenylpropanoid glycoside and iridoid glucoside, on CCl₄-induced liver damage. Male Wistar rats were randomly divided into six groups of ten each. While the first group was maintained as normal control, groups II–VI were administered 0.5 ml/kg CCl₄ (model), 100 mg/kg BRE plus CCl₄, 200 mg/kg BRE plus CCl₄, 50 mg/kg silymarin plus CCl₄ and 200 mg/kg BRE, respectively. CCl₄ challenge not only elevated the serum marker enzyme activities and reduced albumin (ALB) level but also increased liver oxidative stress, as evidenced by elevated lipid hydroperoxide (LOOH) and malondialdehyde (MDA) concentrations, combined with suppressed potential of hepatic antioxidative defense system including superoxide dismutase (SOD), glutathione peroxidase (GPx) activities and reduced glutathione (GSH) content. Furthermore, serum tumor necrosis factor-α (TNF-α), hepatic nitrite level, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein contents were elevated while cytochrome P450 2E1 (CYP2E1) expression and function were inhibited. Preadministration of BRE not only reversed the significant changes in serum toxicity markers, hepatic oxidative stress, xenobiotic metabolizing enzymes and proinflammatory mediators induced by CCl₄ but also restored liver CYP2E1 level and function. Interestingly, the protein expression of heme oxygenase-1 (HO-1) was further elevated by BRE treatment, which was markedly increased after CCl₄ challenge. These results demonstrate that BRE exhibits protective effect on CCl₄-induced acute hepatic injury via, at least in part, reduced oxidative stress, suppressed inflammatory responses and induced HO-1 protein expression combined with improved CYP2E1 level and function in liver.     

Evaluation of the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward against carbon tetrachloride induced liver injury

The present study was designed to demonstrate the antioxidant and hepatoprotective effect of Majoon-e-Dabeed-ul-ward, a Unani herbal formulation. The Majoon-e-Dabeed-ul-ward (MD) at the doses of 250, 500 and 1000 mg/kg, p.o. was administered after carbon-tetrachloride (CCl₄; 1.5 ml/kg, i.p. once only) intoxication. Treatment with MD at three doses brought the levels of aspartate transaminase, alanine transaminase, albumin and urea in dose dependent manner. Signification reduction was found in TBARS content and restored the level of reduced glutathione, adenosine triphosphatase, and glucose-6-phosphatase in liver. Therapy of MD showed its protective effect on biochemical and histopathological observation at all the three doses in a dose dependent manner. The study conducted showed that MD possesses strong hepatoprotective activity as decrease the hexobarbitone sleep time and improvement in physiological parameter, excretory capacity (BSP retention time) was seen. DPPH and H₂O₂ scavenging effects indicated its potent antioxidant activities. The results revealed that MD could afford significant dose-dependent protection against CCl₄ induced hepatocellular injury.     

Hepatoprotective activity of cultured mycelium of Morel mushroom,Morchella esculenta

The hepatoprotective activity of cultured mycelium of morel mushroom Morchella esculenta against CCl₄ and ethanol induced chronic hepatotoxicity was investigated. Hepatotoxicity was induced by challenging the animals with CCl₄ (1:5, v/v, 3.75 ml/kg body weight, i.p., 30 doses) and ethanol (36%, v/v, 6 ml/animal, p.o., 35 doses) and the extract was administered at two concentrations (250 and 500 mg/kg body weight). Hepatoprotection was evaluated by determining the activities of liver function marker enzymes and antioxidant status of liver and also by histopathological observations of liver tissue. Administration of both ethanol and CCl₄ elevated the levels of liver function enzymes, GOT, GPT and ALP in serum drastically. The treatment with the extract decreased the elevated serum GOT, GPT and ALP activities in a dose dependent manner. The extract also restored the depleted levels of antioxidants in liver consequent to CCl₄ and ethanol challenge. The results indicated that aqueous-ethanolic extract of M. esculenta mycelium possessed significant hepatoprotective activity. The conclusion is also supported by the biochemical determinations and histopathological observations. The findings thus suggest the potential therapeutic use of morel mushroom mycelium as a novel hepatoprotective agent.     

Dose- and time-dependent effects of luteolin on carbon tetrachloride-induced hepatotoxicity in mice

Carbon tetrachloride (CCl₄) is a well-known model compound for producing chemical hepatic injury. This study investigated the protective effects of the flavonoid luteolin on the CCl₄-induced hepatotoxicity in mice. Luteolin dissolved in dimethyl sulfoxide (DMSO) was administered intraperitoneally (i.p.) at 5 or 50 mg/kg as a single dose, and once daily for 2 consecutive days. Two hours after the final treatment, the mice were treated with CCl₄ (20 mg/kg, i.p.). CCl₄-induced hepatotoxicity was reduced in a dose- and time-dependent manner, as determined by decreased serum aminotransferase activities and liver histopathology. CCl₄ intoxication resulted in an overexpression of heat shock protein gp96 in the mice liver, which was strongly attenuated by luteolin pretreatment. Luteolin has also decreased oxidative stress produced by CCl₄, as suggested by improvement in the Cu/Zn superoxide dismutase activity. The effect of luteolin on myeloperoxidase, an indicator of inflammatory cell infiltration, was also investigated. Treatment of the mice with luteolin resulted in a significant decrease in the myeloperoxidase activity. The hepatoprotective effect of luteolin against CCl₄ hepatotoxicity was higher in animals pretreated with luteolin for 2 consecutive days. This suggests that the protection might be due to induction of some adaptive mechanisms. The data indicate that luteolin could be effective in protecting mice from the hepatotoxicity produced by CCl₄.     

The effects of grape seed and colchicine on carbon tetrachloride induced hepatic damage in rats

This study aims to determine the effects of grape seed and colchicine on carbon tetrachloride (CCl₄) induced hepatic damage and on some serum biochemical parameters. Sixty male Wistar albino rats (200–250 g) were randomly divided into six groups (ten rats/group) and included the control group the group were given isotonic sodium chloride (1 mL/kg b.w) intraperitonealy (i.p.), group 2 the group treated i.p. injection of CCl₄ (1.0 mL/kg b.w) in corn oil twice in the first week, Groups 3 and 4 injected with CCl₄ as described for group 2 and the rats were orally given (100 mg/kg b.w) GSE and i.p. injected (10 μg/rat) with colchicine for four weeks, respectively and groups 5 and 6 were the grape seed and colchicine control groups in which rats were orally given grape seed (100 mg/kg b.w) and i.p. injected with colchicine (10 μg/rat), respectively. Anorexia, weight loss, motionlessness and hepatic colour variation at necropsy were observed in groups 2, 3, and 4. Hyperemia, focal bleeding, fat degeneration, changes ranging from degenerative to necrotic, increase in connective tissue elements, pronounced in portal sites in particular, and infiltration of lymphoid series cell observed in the livers of the rats in group 2, treated with CCl₄. Histological hepatic changes in the rats in group 3 and 4 were similar to those in group 2. The levels of serum total protein, albumin and globulin decreased in groups 2, 3, and 4, compared with groups 1, 5 and 6; aspartate transaminase (ALT) activities increased. The lowest alkaline phosphatase (ALP) activities were in groups 4 and 5. We concluded that GSE and colchicine have not sufficient ameliorative effects to CCl₄ induced acute hepatic damage.     

Anzer honey prevents N-ethylmaleimide-induced liver damage in rats

N-ethylmaleimide (NEM) is a sulphydryl blocker which impairs the sulphydryl dependent antioxidant system (mainly glutathione) in the body by alkylating endogenous sulphydryls. This study was designed to investigate the effects of Anzer honey on NEM-induced liver injury in rats. Thirty female Wistar albino rats were divided equally into three groups. Group 1: control; Group 2: NEM; Group 3: Anzer honey+NEM. NEM (0.075 mg kg^?1) was given to both group 2 and 3 administered subcutaneously (s.c.) for 30 days. The animals in the Anzer honey+NEM group were treated with Anzer honey at a dose of 0.275 g kg^?1, (p.o.) at 1 h prior to every NEM injection. At the end of the 30 day treatment period, liver samples were taken for determination of the glutathione levels and histological examination. NEM treatment alone caused a significant reduction of the liver glutathione levels in group 2. Furthermore, NEM treatment caused congestion and mononuclear cell infiltration in the liver when compared to the control group. In group 3, Anzer honey treatment reversed all the changes in glutathione level, as well as histopathological alterations, normally induced by NEM. The findings imply that depletion of glutathione concentration plays a causal role in NEM-induced liver injury, and that the hepatoprotective effect of Anzer honey may be mediated through sulfhydryl-sensitive processes. They further imply that it may also possess antioxidant properties.     

Attenuation of CCl4-induced hepatic oxidative stress in rat by Launaea procumbens

Antioxidant effects of Launaea procumbens methanol extract (LPME) were evaluated against CCl₄-induced oxidative stress in liver of rat. 48 male rats were equally divided in to 8 groups (06 rats each). Group I (control) remained untreated, while Group II was given vehicles (olive oil and DMSO). Animals of Groups III, IV, V, VI and VII were injected intraperitoneally with CCl₄ (3 ml/kg b.w.; i.p., 20% CCl₄/olive oil) twice a week for four weeks. Group III received only CCl₄ while Group IV was given rutin (50 mg/kg b.w.). Group V, VI and VII were administered LPME at a dose of 100, 150 and 200 mg/kg b.w., respectively. Animals of Group VIII received LPME (200 mg/kg b.w.) alone. Oxidative stress induced with CCl₄ in liver was evident by a significant increase in triglycerides, total cholesterol, LDL-cholesterol, and enzymatic activities of AST, ALT, ALP, LDH, γ-GT activities in serum. Level of lipid peroxidation, nitrite, and hydrogen peroxide concentration, DNA injuries in liver samples was also increased with CCl₄. GSH concentration in liver was significantly decreased, as were the activities of antioxidant enzymes; CAT, POD, SOD, GSH-Px, GST, GSR, QR. Co-treatment of rats with LPME and rutin prevented all the changes observed with CCl₄. Hepatic lesions and telomerase activity induced with CCl₄ was also suppressed with LPME and rutin. It is suggested that LPME effectively prevented the CCl₄-induced oxidative injuries in liver, possibly through antioxidant and/or free radical scavenging effects of flavonoids and phenolic compounds in the extract.     

Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1 ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of the extract. Rats were treated with aqueous extract of H. enneaspermus at a dose of either 200 or 400 mg/kg after division into pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 h after CCl4 intoxication) groups. Pre-treatment and post-treatment with aqueous extract of H. enneaspermus showed significant hepatoprotection by reducing the aspartate transaminase, alanine transaminase, and alkaline phosphatase enzymatic activities and total bilirubin levels which had been raised by CCl4 administration. Pre- and post-treatment with aqueous extract significantly decreased hepatic lipid peroxidation as well as producing a corresponding increase in tissue total thiols. Post-treatment with aqueous extract improved ceruloplasmin levels. The histopathological examination of rat liver sections treated with aqueous extract confirms the serum biochemical observations. The present study results demonstrate the protective, curative and anti-oxidant effects of H. enneaspermus aqueous extract used against CCl4-induced hepatotoxicity in rats, and suggest a potential therapeutic use of H. enneaspermus as an alternative for patients with acute liver diseases.     

Establishment of a liver fibrosis model in cynomolgus monkeys

Hepatic fibrosis, resulted from hepatoxicity and other diseases such as diabetes, is an important pathological characteristic of chronic liver diseases. Establishment of hepatic fibrosis animal models is of great importance and a prerequisite for human clinical studies. The common models for liver fibrosis are often established in lower small animals such as rats, but non-human primates are a much better model for human diseases because of the physiological similarity with humans. In this study, we investigated the method to induce liver fibrosis in cynomolgus monkeys using carbon tetrachloride (CCl₄) and to establish a model that more closely mimics human liver fibrosis. We successfully established the liver fibrosis model in 15 of the 20 cynomolgus monkeys (success rate 75%), by CCl₄ administration at a dose of 1.0 mL/kg (400 mL/L) twice a week. Liver biopsy showed that liver fibrosis progressed with time and gradually advanced into early-stage cirrhosis in 10 of the 15 established models at 16 weeks. Our study provides a better research platform for the prevention and treatment of chronic liver diseases.     

Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats

The present study was to evaluate the hepatoprotective effect of hesperetin (HTN) on cadmium (Cd) induced hepatotoxicity in male Wistar rats. Administration of Cd (3 mg/kg body weight/day) subcutaneously for 21 days, the levels of hepatic markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and bilirubin were significantly increased in serum. The levels oxidative stress markers, thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), conjugated dienes (CD) and protein carbonyl content (PCC) were also significantly increased while the levels of vitamin C, vitamin E, reduced glutathione (GSH), total sulphydryl group (TSH) and the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) were significantly decreased in the liver of Cd intoxicated rats. HTN, a flavanone in citrus fruits, administrated orally along with Cd injection for 21 days, significantly revert back the status of serum hepatic markers, oxidative stress markers and antioxidant markers in the liver tissue to near normal level in a dose dependent manner. HTN at a dose of 40 mg/kg body weight/day exhibits significant (p < 0.05) hepatoprotection compared with other two doses (10 and 20 mg/kg body weight/day). The histopathological studies in the liver of rats also supported that HTN (40 mg/kg) markedly reduced the toxicity of Cd and preserved the histoarchitecture of the liver tissue to near normal. Thus, the results suggest that HTN acts as a potent hepatoprotective agent against Cd induced hepatotoxicity in rats.     

Hepatoprotective effects of Vernonia amygdalina (astereaceae) in rats treated with carbon tetrachloride

The possible modulatory effect of methanolic extract of Vernonia amygdalina (MEVA), a plant widely consumed in the tropics and used locally in the treatment of fever, jaundice, stomach disorders and diabetes on the toxicity of CCl₄, was investigated in male rats.Oral administration of CCl₄ at a dose of 1.2 g/kg body weight 3 times a week for 3 weeks significantly induced marked hepatic injury as revealed by increased activity of the serum enzymes ALT, AST, SALP and γ-GT. Methanolic extract of V. amygdalina administered 5 times a week for 2 weeks before CCl₄ treatment at 250 and 500 mg/kg doses of the extract ameliorated the increase in the activities of these enzymes. Likewise the methanolic extract of V. amygdalina reduced the CCl₄-induced increase in the concentrations of cholesterol, triglyceride and phospholipid by 37.8%, 30.6% and 8.5%, respectively, and a reduction in the cholesterol/phospholipids ratio. These parameters were however increased at 750 mg/kg extract pretreatment. CCl₄-induced lipid peroxidation was likewise attenuated by 57.2% at 500 mg/kg dose of the methanolic extract of V. amygdalina. Similarly, administration of the extract increased the activities of the antioxidant enzymes: superoxide dismutase, glutathione S-transferase and reduced glutathione concentration significantly at 500 mg/kg (P<0.05) and catalase activity at 500–1000 mg/kg doses. These results suggest that methanolic extract of V. amygdalina leaves posseses protective effect against CCl₄-induced hepatotoxicity by the antioxidant mechanism of action.     

Protective effect of vitamin E and selenium combination on deltamethrin-induced reproductive toxicity in male rats

The current study was performed to assess the adverse effect of deltamethrin (DLM) on reproductive organs and fertility in male rats and to evaluate the protective role of vitamin E (VE) and selenium (Se) combination in alleviating the detrimental effect of DLM on male fertility. The lethal dose 50 (LD₅₀) of DLM for male rats was estimated at 6 mg/kg bwt. Thirty male albino rats (10-weeks-old) were divided into three groups (10 rats each): Control group was injected subcutaneously with 2 ml/kg bwt saline twice weekly and was daily administered 2 ml distilled water intra-gastrically; DLM-treated group received 0.6 mg/kg bwt (1/10 LD₅₀) DLM intra-gastrically once daily; DLM + VE/Se-treated group was injected subcutaneously with 1.2 mg/kg bwt Viteselen^®15 (VE/Se) twice weekly with concurrent daily administration of 0.6 mg/kg bwt (1/10 LD₅₀) DLM intra-gastrically. The experiment was conducted for 60 consecutive days. DLM caused a significant reduction in reproductive organs weights, sperm count, sperm motility percent, alive sperm percent, serum testosterone level and testicular reduced glutathione concentration (GSH). DLM-treated group showed a significant increase in sperm abnormalities and testicular malondialdehyde (MDA) concentrations. Histopathologically, DLM caused impairments in testes, epididymes and accessory sex glands. Conversely, treatment with VE/Se combination improved the reduction in the reproductive organs weights, sperm characteristics, DLM-induced oxidative damage of testes and the histopathological alterations of reproductive organs. Results indicate that DLM exerts significant harmful effects on male reproductive system and that the concurrent administration of VE/Se partly reduced the detrimental effects of DLM on male fertility.     

Protective effect of Sonchus asper extracts against experimentally induced lung injuries in rats: A novel study

In this study, protective effects of methanol extract (SAME) were evaluated against carbon tetrachloride induced oxidative stress in lungs. Male Sprague–Dawley rats were orally fed with various doses (100, 200 mg/kg body weight) of SAME and (50 mg/kg body weight) of rutin after 48 h of CCl₄ treatment (3 ml/kg body weight, 30% in olive oil) biweekly for 4 weeks. The results showed that administration of extracts and rutin significantly restored lung contents of reduced glutathione and activities of catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase, quinine reductase were reduced while lipid peroxide, hydrogen peroxide, nitrite, DNA fragmentation% and activity of γ-glutamyl transferase, increased by CCl₄, were reversed towards the control levels by the supplement of Sonchus asper extracts and rutin. Lung histopathology showed that S. asper extracts and rutin reduced the incidence of lung lesions induced by CCl₄ in rats. These results suggest that S. asper fractions and rutin could protect lung against the CCl₄-induced oxidative damage in rats.     

Antioxidant effects of Citharexylum spinosum in CCl4 induced nephrotoxicity in rat

The present study was carried out to evaluate the antioxidant effect of the chloroform extract of Citharexylum spinosum (CSCE) (Family: Verbenaceae) leaves in Sprague–Dawley male rats. The different groups of animals were administered with carbon tetrachloride (CCl₄; 20% in olive oil, 2 ml/kg body weight) 7 doses (i.p.) at 48 h interval. The CSCE at the doses of 100 and 200 mg/kg or silymarin at a dose of 50 mg/kg were administered intragastrically after 24 h to the CCl₄ treated rats. The effect of CSCE or silymarin on urine and serum markers (urea, creatinine, creatinine clearance, protein, albumin, urobilinogen and nitrite) was measured in CCl₄-induced nephrotoxicity in rat. Further, the effects on lipid peroxidation (TBARS), enzymatic antioxidants (catalase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, glutathione reductase) and non-enzymatic antioxidant glutathione (GSH) were estimated in the kidney samples. The CSCE and silymarin produced significant renal protective effects by restoring the concentration of urine and serum markers. Activity level of antioxidant enzymes and GSH contents were increased while lipid peroxidation (TBARS) was decreased, dose dependently with CSCE and silymarin. Decrease in body whereas increase in kidney weight induced with CCl₄ was restored with CSCE and silymarin. Chemical composition of CSCE indicated the presence of flavonoids, terpenoids, alkaloids and very low amount of saponins. Total flavonoids estimated were (127 ± 14.6) as rutin equivalent mg/g of the extract. From these results, it is suggested that CSCE possesses potent nephroprotective and antioxidant properties.     

Effect of different doses of hexavalent chromium on mandibular growth and tooth eruption in juvenile Wistar rats

Not only workers employed at industrial plants are exposed to intoxication with the element they manipulate, the population at large is also at risk of suffering health problems caused by contaminating wastes inadequately treated for their safe disposal. As a result certain toxic substances, such as hexavalent chromium,has reached the general population including children. The present study sought to evaluate the effect of intoxication with hexavalent chromium on body and mandibular growth and tooth eruption in suckling Wistar rats. Potassium dichromate was administered by gavage in a dose of 6.25 or 12.5 mg/kg body weight (b.w.) to one of the two groups of 4-day-old Wistar rats during 10 days. Our results showed that the effects of chromium are dose-dependent. Morphometric studies of body growth showed lower body weight in both experimental groups and shorter tail length in animals receiving 12.5 mg/kg b.w. dose of chromium, compared with controls. All parameters of mandibular growth were lower in the experimental group receiving 12.5 mg/kg b.w. of chromium. Differences in tooth eruption were observed at the level of the first molar in animals receiving 12.5 mg/kg and of the second molar in those receiving 6.25 mg/kg b.w. of chromium. Chromium was found to affect all the studied parameters.     

Radical scavenging abilities and hepatoprotective effect of [N,N′-Bis (salicylidene) ethane-1, 2-diaminato] oxovanadium (IV) complex in CCl4-treated rats

The antioxidant activity of [N, N′-Bis (salicylidene) ethane-1, 2-diaminato] oxovanadium (IV) complex (VO-salen complex) was evaluated using different in vitro evaluating systems including superoxide anion (O₂^?) and hydrogen peroxide (H₂O₂) scavenging activities. In addition, the inhibitory effects of this compound on protein oxidation and inhibition of Fe²⁺/ascorbate-induced lipid peroxidation were studied using rat liver homogenate. In vitro results revealed that the VO-salen complex has strong inhibitory effects on protein oxidation and lipid peroxidation of the liver homogenate along with a concentration-dependent quenching of H₂O₂ and O₂^? radicals. In an in vivo approach, hepatoprotective potential of the VO-salen complex against liver damages induced by CCl₄ treatment was also investigated. After intraperitoneal injection of CCl₄ to rats, various biochemical changes associated with liver injury and/or oxidative stress were measured. The results showed that the sera levels of ALT, AST, ALP and the content of hepatic thiobarbituric acid reactive substances (TBARS) were all increased and the glutathione (GSH) content and the hepatic superoxide dismutase (SOD) and catalase (CAT) activities were decreased in CCl₄-treated rats. However, simultaneous treatment of rats with VO-salen (0.6 mg/kg) and CCl₄ significantly attenuated the sera levels of ALT, AST, ALP and the hepatic TBARS content. In addition, by VO-salen therapy, the hepatic SOD and CAT activities and the GSH content were all restored back almost to their normal levels. The liver damages were also significantly ameliorated as compared to the CCl₄-treated rats. Based on these results, the VO-salen complex might be considered as an effective antioxidant and hepatoprotective agent suitable for further biological evaluation.     

Puerarin protects the rat liver against oxidative stress-mediated DNA damage and apoptosis induced by lead

Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. In this study, we valuated the protective effect of puerarin against lead-induced oxidative DNA damage and apoptosis in rat liver. A total of forty male Wistar rats (8-week-old) was divided into 4 groups: control group; lead-treated group (500 mg Pb/l as the only drinking fluid); lead + puerarin treated group (500 mg Pb/l as the only drinking fluid plus 400 mg PU/kg bwt intra-gastrically once daily); and puerarin-treated group (400 mg PU/kg bwt intra-gastrically once daily). The experimental period was lasted for 75 successive days. Our data showed that puerarin significantly effectively improved the lead-induced histology changes in rat liver and decreased the serum ALT and AST activities in lead-treated rats. Puerarin markedly restored Cu/Zn-SOD, CAT and GPx activities and the GSH/GSSG ratio in the liver of lead-treated rat. Furthermore, the increase of 8-hydroxydeoxyguanosine induced by lead was effectively suppressed by puerarin. The enhanced caspase-3 activity in the rat liver induced by lead was also inhibited by puerarin. TUNEL assay showed that lead-induced apoptosis in rat liver was significantly inhibited by puerarin, which might be attributed to its antioxidant property. In conclusion, these results suggested that puerarin could protect the rat liver against lead-induced injury by reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage.     

Arsenic induced toxicity and histopathological changes in gill and liver tissue of freshwater fish,tilapia (Oreochromis mossambicus)

Acute toxicity of arsenic to tilapia (Oreochromis mossambicus) and its histopathological impacts on gill and liver tissue were evaluated. The median lethal concentration (96 h; LC₅₀) of arsenic (NaAsO₂) was calculated as 28.22 ppm in repeated semi static test method. Fish were exposed to 3 ppm, 28 ppm and 56 ppm concentrations of NaAsO₂ and gill and liver samples were collected after 48 h, 96 h and 192 h of exposure. The changes in gill were characterized by epithelial hyperplasia, epithelial lifting and oedema, lamellar fusion, aneurism, desquamation and necrosis, whereas, the liver tissue showed focal lymphocytic and macrophage infiltration, congestion, vacuolization and shrinkage of hepatocytes, dilation of sinusoids, cloudy swelling, vacuolar degeneration, focal necrosis and nuclear hypertrophy. The result showed that acute arsenic toxicity severely affects the normal behavior and vital organs which is deleterious for the exposed fish.     

Expression patterns of heat shock protein 25 in carbon tetrachloride-induced rat liver injury

Heat shock protein 25 (Hsp25) is a molecular chaperone playing roles in cytoprotection. We investigated the distribution and localization of Hsp25 expression in CCl₄-induced rat hepatic lesions; liver samples were obtained from 3 h to 10 days after a single oral administration of CCl₄. Immunohistochemically, Hsp25-positive hepatocytes started to appear in the perivenular area at 6 h after CCl₄ administration. Their number and strength increased till day 1. Expression of Hsp25 mRNA significantly increased after 3 h and proceeded to increase with time till day 1. Apoptotic hepatocytes were detected around the perivenular area after 6 h. The area where Hsp25-positive hepatocytes were observed till day 1 corresponded to the area where apoptotic hepatocytes were seen. On days 2 and 3, degenerative and/or necrotic hepatocytes in the perivenular area were replaced by macrophages reacting to ED1 (for CD68) and ED2 (for CD163); Hsp25 expression was seen in hepatocytes around the perivenular area and there was a close relationship of reactive macrophages with Hsp25-positive hepatocytes, suggesting a potential role for Hsp25 in suppressing injury by inflammation. The mRNA expression of tumor necrosis factor-α, monocyte chemoattractant protein-1 and osteopontin, which can be produced by infiltrating macrophages, corresponded to that of Hsp25 from day 1 to day 3; these factors might be related to the induction of Hsp25 expression. The shift of the Hsp25 expression pattern in the liver lesion might have depended on microenvironmental conditions evoked by interactions between necrobiotic hepatocytes and infiltrating macrophages. Thus, Hsp25 expression analyses should be beneficial for evaluations of hepatotoxicants.     

Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury

ObjectiveOverdose of acetaminophen (APAP) can lead to severe liver injury in humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by several cell types. In this study, we aimed to evaluate whether PTX-3 is a potential biomarker in the identification of APAP-induced liver injury.Materials and methodsThirty adult male Wistar rats were randomly divided into three groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg) group rats were given APAP by gastric tube. Liver tissues and blood samples were obtained for biochemical and histopathological analysis. Biochemical parameters, plasma and liver PTX-3 levels and degree of liver necrosis were measured in all groups.ResultsAPAP treatments caused necrosis in liver and accompanied by elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared with control group (7.5 ± 3.3 ng/mg protein), mean liver PTX-3 concentrations were 14.1 ± 3.0 (p = 0.032) and 28.5 ± 8.2 (p < 0.001) ng/mg protein, respectively. All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%, 40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the APAP-1 and APAP-2 groups were higher than the group of control (p < 0.001 and p < 0.001, respectively).ConclusionsPTX-3 may have a role in the APAP-induced liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic necrosis might be a marker of acute histological liver damage. Further prospective studies are necessary to clarify the prognostic value of liver PTX-3 for prediction of histological hepatic necrosis in the APAP-induced liver injury.