Hepatotoxicity In Male Rats Research Articles

Protective Effect of Phenolic Extract of Urtica dioica leaves against Carbon Tetra-Chloride Induced Hepatotoxicity in Male Rats

The present study concluded phenolic extract of Urtica dioica leaves the protecting effect against CCL4 induced hepatotoxicity. The present study refered to a significant increase (P=0.05) in serum levels of liver enzymes (ALP, ALT, AST), and bilirubin level in carbon tetrachloride-induced groups as compared with control group. The current study revealed the occurrence of a significant decrease (P=0.05) in the level of liver enzymes When administered by phenolic extract for (two and three months) compared with carbon tetrachloride group. Highly significant (P=0.05) with the concentration of the (500mg/kg) for phenolic extract, and no significant observed between phenolic extract for (two and three months) and before and after induced by the carbon tetrachloride. Histological section of liver male rat induced by carbon tetrachloride for two months showed inflammation and degeneration of hepatocytes, however, the histological section is shown chronic inflammation, severe congestion and haemorrhage, accumulation of fat, degeneration and necrosis, severe degeneration of hepatocytes, and appearance fibroblast for three months. The histopathological changes of liver in male rats treated with both doses (250 and 500 mg/kg) of a phenolic extract of Urtica dioica leaves showed the normal architecture of hepatocytes.

The potential protective effect of α-lipoic acid against nanocopper particle-induced hepatotoxicity in male rats.

The present research task is aimed to evaluate the role of exogenous α-lipoic acid (ALA) (100 mg/kg body weight) as hepatoprotective and potent antioxidant in amelioration of copper nanoparticle (CNP)-induced hepatotoxicity. Forty male rats were randomly assigned into four equal groups: group I (control), group II received CNPs, group III received CNPs + ALA, and finally group IV received ALA for 2 months. At the end of the experimental period, the rats were decapitated, and blood and liver tissue samples were collected for measurement of liver function tests, antioxidant status, lipid peroxidation (LPO), copper content, expression of some apoptotic genes, and histopathological analysis. CNPs induced marked hepatic damages as evident by severe alteration in hepatic biomarkers. This was accompanied by a significant elevation in hepatic LPO and induced nitric oxide, copper content, and expression level of apoptotic genes (C-myc and C-jun). In contrast, marked depletion for antioxidant parameters was detected. These findings were confirmed with severe pathological alterations. Coadministration of ALA as a powerful antioxidant attenuates the hepatotoxic effects of CNPs through improvement of liver parameters, oxidative status, genetic changes, and preservation of liver integrity through histopathological analysis. These results suggest that consumed ALA could be used as an applicable hepatoprotective agent against oxidative damage mediated by nanoparticles intoxication.

The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

BackgroundLiver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl4 induced liver damage in male rats.MethodsForty males of a new model of albino rats (Wistar strain) (175–205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube.ResultsThe positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation.ConclusionThis study revealed that olive oil and N. sativa oil have a protective effect against CCl4-induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

Aqueous extract of Monodora myristica ameliorates cadmium-induced hepatotoxicity in male rats.

In recent years, indigenous medicinal plants exhibiting diverse biological activities have been explored in the amelioration of hepatotoxicity. This study investigates the protective effect of Monodora myristica (MM) on cadmium-induced liver damage in experimental animals. Male Wistar albino rats were maintained on 200 mg/L cadmium: Cd (Cd as CdCl2) in the animals’ main drinking water to induce hepatotoxicity. Added to this, the animals received aqueous extracts of MM at a dose of 200 or 400 and 20 mg/kg bw of Livolin forte (LF) for 21 days. At the end of the experiment, levels of serum enzyme biomarkers (alanine transaminase, alkaline phosphatase and aspartate transaminase) as well as total cholesterol (TC), triacylglyceride (TG) and malondialdehyde were significantly raised in the cadmium treated groups. Conversely, cadmium treatment elicited noticeable decrease in hepatic enzymatic and non-enzymatic antioxidants (reduced glutathione: GSH, catalase: CAT, superoxide dismutase: SOD). Co-treatment with MM at varying doses as well as LF considerably decreased the elevated levels of the serum biomarkers as well as TC, TG and malondialdehyde in the cadmium-treated groups in a dose dependant manner. Additionally, MM exhibited reversal potential on cadmium-toxicity at the tested doses as its administration was accompanied by a pronounced increase in GSH, SOD, and CAT levels. Histopathological results were parallel to these findings. These results demonstrates that aqueous extracts of MM is effective in the amelioration of hepatic damages arising from cadmium-induced toxicity, indicating that the antioxidant bio-constituents of MM play an important role in the prevention of liver toxicity possibly by inhibiting bioaccumulation of free radicals in animal models.

The mitigative effect of Raphanus sativus oil on chromium-induced geno- and hepatotoxicity in male rats

To study the impact of radish oil on the possible genotoxic and hepatotoxic effects of hexavalent chromium, male rats were divided into 4 groups. Group 1 served as control, group 2 received radish oil at the recommended human therapeutic dose (0.07mL/kg) by gavage, group 3 received sodium dichromate dihydrate (SDD) 520mg/L in drinking water, and group 4 received both SDD and radish oil as previously mentioned in groups 2 and 3. All treatments were continued for six months. The results revealed that chromium exposure promoted oxidative stress with a consequently marked hepatic histopathological alterations, increased serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) activities, alfa fetoprotein (AFP) levels, and micronucleated erythrocytes (MNE) % in peripheral blood. Moreover, COMET assay of hepatic DNA revealed that SDD exposure significantly decreased the intact cells %, head diameter, and head DNA % compared to control, indicating DNA damage. However, radish oil co-administration with SDD resulted in marked amendment in the altered parameters as detected by improved liver function markers (ALT and ALP) and AFP level, decreased lipid peroxidation, increased antioxidant markers, inhibited hepatic DNA damage and restored the hepatic histology by preventing the appearance of the altered hepatocytes’ foci and decreasing chromium induced histopathological lesions. It could be concluded that radish oil was able to provide a convergent complete protection against the geno- and hepatotoxicity of chromium by its potent antioxidant effect.

Exploring the protective effect of silymarin against flutamide-induced hepatotoxicity in male rats

Exploring the protective effect of silymarin against flutamide-induced hepatotoxicity in male rats

ANTIOXIDANT AND HEPATOPROTECTIVE EFFECT OF Cinnamomum zeylanicum OIL AGAINST PARACETAMOL INDUCED HEPATOTOXICITY IN MALE RATE.

The main objective of this study is a trial to investigate the efficiency of cinnamomum zeylanicum (cinnamon) oil against paracetamol induced hepatotoxicity in male rats. The bark cinnamon was hydrodistilled using Clevenger,s apparatus to yield essential oil 2.3%.Total phenolic compounds and scavenging radical effect on 2, 2-diphenylpicrylhydrazyl (DPPH) were investigated. Gas chromatographic- mass spectroscopy fractionated cinnamon bark volatile oil to six components accounting for 100% of total amount. Cinnamaldehyde was found as the major component 68.01% followed by Eugenol 11.47, Cinnamyl alcohol 6.52% , α- murolene 5.24%, δ- cadinen 4.41% and Methyl eugenol 4.35%. Biological experiment was carried out for eight weeks. Results revealed that liver marker enzymes alanine transaminase (ALT) aspartate transaminase (AST), alkaline phosphatase (ALP) were increased. On the other hand serumtotal protein and serum albumin were decreased as well as, lipid profile of total lipids (TL), triglycerides (TAG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) were increased and high density lipoprotein cholesterol (HDL-C)was decreased in paracetamol treated rats(group2). Lipid peroxidation malondialdehyde (MDA) was increased in liver tissue of rats treated with paracetamol, while activities of glutathione peroxidase(Gpx) and Glutathione-S-transferase (GST) were decreased. Cinnamon oil both dose and silymarin showed remarkable hepatoprotective and antioxidant activity against paracetamol induced hepatotoxicity as judged from the serum marker enzymes and antioxidant in liver tissue.

Ameliorating effect of chicory (Chichorium intybus L.) fruit extract against 4-tert-octylphenol induced liver injury and oxidative stress in male rats

The current study was carried out to elucidate the modulating effect of chicory (Cichorium intybus L.) fruit extract (CFR) against 4-tert-OP induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8weeks as follow: group 1: normal control-treated (saline); group 2: chicory fruit extract-treated (100mg/kg); group 3: 4-tert-OP treated; group 4: 4-tert-OP plus chicory fruit extract. The obtained results revealed that rats which received 4-tert-OP showed a significant increase in liver TBARS and bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. While a significant decrease in the levels of GSH, SOD, catalase recorded. On the other hand, CFR extract succeeded to modulate these observed abnormalities resulting from 4-tert-OP as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. Histopathological evidence, together with observed PCNA and DNA fragmentation, supported the detrimental effect of 4-tert-OP and the ameliorating effect of CFR extract on liver toxicity. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by 4-tert-OP compound.

Fenugreek seed powder mitigates cadmium-induced testicular damage and hepatotoxicity in male rats

Cadmium is a potential environmental and industrial pollutant affecting human tissues and organs including liver and testes. The protective role of fenugreek seed powder (FSP) was investigated in male rats subjected to cadmium-induced testicular injury and hepatic dysfunction. Testicular damage and hepatotoxicity were induced by oral administration of cadmium chloride (5mg/kg body weight, once a day) for 7 weeks. FSP was given at 5% w/w in chow diet for 8 weeks, starting 1 week before cadmium administration. FSP intake significantly increased serum testosterone level and testis weight that were reduced by cadmium. FSP also compensated deficits in hepatic and testicular antioxidant defense system, interleukin-4 and nitric oxide levels, reduced serum liver function enzyme activities and suppressed lipid peroxidation in hepatic and testicular tissues resulted from cadmium administration. Additionally, FSP attenuated the cadmium-induced elevations in hepatic and testicular tumor necrosis factor-α and transforming growth factor-beta1 levels as well as cadmium deposition and hydroxyproline content. The protective effect afforded by FSP was mainly due its antioxidant, antifibrotic and anti-inflammatory effects. In conclusion, the results of the present work indicated that FSP may represent a promising medicinal herb to protect hepatic and testicular tissues from the detrimental effects of cadmium.

Protective Effect of Cornus mas Fruits Extract on Serum Biomarkers in CCl4-Induced Hepatotoxicity in Male Rats.

Background:Nowadays attention to use herbs such as cornelian cherry (Cornus mas) is increasing, which contains high levels of antioxidants and anthocyanins. Cornus mas fruits have been used for gastrointestinal and excretory disorders for many years in traditional medicine, also may improve liver and kidney functions, and have protective effects such as anti-allergic, antidiabetic, antibacterial, antimicrobial, antihistamine and antimalarial properties.Objectives:The aim of this study was to investigate protective effects of Cornus mas fruits extract on serum biomarkers in CCl4-induced hepatotoxicity in male rats.Materials and Methods:Hepatotoxicity was induced by administration of carbon tetrachloride (1 mL/kg i.p.) in 1:1 dilution with olive oil. To evaluate the effect of Cornus mas fruits extract on disease progression, serum marker enzymes, serum total protein and albumin and liver lipid peroxidation were determined in CCl4-induced hepatotoxicity.Results:Oral administration of Cornus mas fruits extract to rats for 14 days provided a significant (P < 0.05) hepatoprotection by decreasing elevated serum level of enzymes, total serum protein, albumin and liver lipid peroxidation content.Conclusions:Cornus mas fruit extract effect may be due to including some antioxidant components, which caused membrane stabilizing and normalization of fluctuated biochemical profiles induced by CCl4 exposure. Our results validated the traditional use of Cornus mas in the treatment of liver disorders.

Bromobenzene-induced hepatotoxicity in male rats: the protective effect of flaxseed

The metabolites of bromobenzene (BB) are hepatotoxic. The aim of this study was to determine the efficacy of different doses of flaxseed extract in alleviating BB-hepatotoxicity in male albino rats. Oxidative stress parameters, drug metabolizing enzymes, a pro-inflammatory marker, an apoptotic marker, and DNA fragmentation pattern were also assessed. Animals were divided into five groups treated by intragastric intubation as follows: control, BB-treated 460 mg kg−1 BW alone; three animal groups (III, IV, V) were treated concurrently with 460 mg kg−1 BB daily for 3 weeks and different doses of flaxseeds extract: 100, 200, or 300 mg kg−1 BW. Oral treatment of BB produced a significant decrease in activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase and glutathione levels, while activities of glutathione reductase and drug-metabolizing enzymes; glutathione-S-transferases and cytochrome P450 were enhanced. BB-treatment resulted in enhanced production of nitric oxide and activation of COX-2 and caspase-3. Pre-treatment with different doses of flaxseeds extract prior and during BB-treatment protected liver against BB-induced hepatotoxicity. The lower dose of flaxseed extract (100 mg kg−1) was most effective one.

Hepatoprotective Effect of Otostegia persica Boiss. Shoot Extract on Carbon Tetrachloride-Induced Acute Liver Damage in Rats.

In this study, the hepatoprotective effect of the methanol extract of aerial parts (shoot) from Otostegia persica Boiss (Golder) was investigated against the carbon tetrachloride (CCl4)-induced acute hepatotoxicity in male rats. Liver damage was induced through the oral administration of 50% CCl4 in liquid paraffin (2.5 mL/Kg bw, per os) 60 min after the administration of the methanol extract of O. persica shoot (in 200, 300, 400 mg/Kg bw doses) and assessed using biochemical parameters (plasma and liver tissue malondialdehyde (MDA), transaminase enzyme levels in plasma [aspartate transaminase (AST), alanine aminotransferase (ALT)] and liver glutathione (GSH) levels). Results show that the methanol extract of O. persica shoot is active at 300 mg/Kg (per os) and it possess remarkable antioxidant and hepatoprotective activities. Additionally, histopathological studies verified the effectiveness of this dose of extract in acute liver damage prevention.

Curative potential of aqueous extract of &lt;i&gt;Ziphus mauritiana&lt;/i&gt; leaf against chronic alcohol-induced hepatotoxicity in male rats

The curative potential of the aqueous extract of Ziziphus mauritiana leaf was evaluated in chronic alcohol-induced liver damage. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and uric acid (UA) were significantly (p Ziziphus mauritiana significantly (p Ziziphus mauritiana extract. Histopathological section of rat liver post-treated with Ziziphus mauritiana extract enhanced quick recovery from alcohol-induced hepatotoxicity compared to untreated group. Curative potential of the aqueous extract of Ziziphus mauritiana leaf could be due to its ability to stimulate increased antioxidant activity and reduction in the level of hepatic lipid peroxidation. Key words: Chronic alcohol, hepatotoxicity, post-treatment, Ziziphus mauritiana , antioxidants.

Effect of Nigella sativa Oil and Activated Charcoal as Antioxidant on Verrucarin J induced Hepatotoxicity in Male Rats

El-Sawi, N.M. and Gashlan, H.M. 2010. Effect of Nigella sativa oil and activated charcoal as antioxidant on verrucarin J induced hepatotoxicity in male rats. J. Appl. Anim. Res., 37: 285–288. With a view to study the effects of exposure to verrucarin J and their amelioration by Nigella sativa oil or Charcoal, male rats were treated with a sublethal dose of verrucarin J (0.9mg/kg intraperitoneally). verrucarin J showed an increase (P<0.01) in blood and liver tissue levels of TBARs, SOD and 5 nucleotidase. These were decreased by and large by Nigella sativa or charcoal, the former being more effective. Similarly, the decrease in levels of glucose and zinc in blood as well as RGSH and glucose-6-phosphate dehydrogenase in liver tissue (P<0.01) by verrucarin J was improved partially by the two treatments. It is concluded that the treatment of rats with Nigella sativa oil or Charcoal ameliorated the adverse effects of toxin but the results suggest that Nigella sativa oil may be used as antioxidant and antidote, rather than charcoal, for verrucarin J in rats.

Ameliorating effect of chicory ( Cichorium intybus L.)-supplemented diet against nitrosamine precursors-induced liver injury and oxidative stress in male rats

The current study was carried out to elucidate the modulating effect of chicory ( Cichorium intybus L.)-supplemented diet against nitrosamnine-induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8 weeks as follow: group 1 served as control; group 2 fed on chicory-supplemented diet (10% w/w); group 3 received simultaneously nitrosamine precursors [sodium nitrite (0.05% in drinking water) plus chlorpromazine (1.7 mg/kg body weight)] and group 4 received nitrosamine precursors and fed on chicory-supplemented diet. The obtained results revealed that rats received nitrosamine precursors showed a significant increase in liver TBARS and total lipids, total cholesterol, bilirubin, and enzymes activity (AST, ALT, ALP and γ-GT) in both serum and liver. While a significant decrease in the levels of GSH, GSH-Rx, SOD, catalase, total protein and albumin was recorded. On the other hand, chicory-supplemented diet succeeded to modulate these observed abnormalities resulting from nitrosamine compounds as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by nitrosamine compounds.

Protective effect of ginger extract against bromobenzene-induced hepatotoxicity in male rats

The bromobenzene (BB)-induced hepatotoxicity comes from its reactive metabolites. The efficacy of different doses of ginger ( Zingiber officinales Rose) extract in alleviating hepatotoxicity was investigated in male albino rats. Oxidative stress parameters were monitored. The drugs metabolizing enzymes; cytochrome P450 and GST, pro-inflammatory marker; COX-2 and the apoptotic marker; caspase-3 were assessed. Animals were assigned to 1 of 5 groups: control group; bromobenzene (460 mg/kg BW) alone, three animal groups 3–5 treated with different doses of ethanolic ginger extract (100, 200, 300 mg/kg BW, respectively) 2 weeks prior bromobenzene (460 mg/kg BW) treatment. Rats received orally ginger extract daily for 21 days whereas bromobenzene treatment for 7 days starting from 15th day of treatment. Oral treatment of BB was found to elicit a significant decrease in the activities of the antioxidant enzymes; SOD, GPx and the GSH level, while the activities of GR and drug metabolizing enzymes; GSTs and Cyt P450 were enhanced. Also, BB-treatment resulted in a great enhanced production of nitric oxide products and activation of COX-2 and caspase-3. Pre-treatment with different doses of ginger extract prior to BB-treatment alleviated its toxic effects on the tested parameters in the three animal groups.

Lipid homeostasis and oxidative stress in the liver of male rats exposed to perfluorododecanoic acid

Perfluorododecanoic acid (PFDoA), a perfluorinated carboxylic acid (PFCA) with twelve carbon atoms, has broad industrial applications and is widely distributed in both wildlife and the environment. Unlike other PFCAs with short carbon chain, however, limited studies have been performed to date on the toxic effects of PFDoA on animals. To determine the hepatotoxicity of PFDoA, male rats were orally dosed by gavage for 14 days with 0, 1, 5, or 10 mg PFDoA/kg/day. Absolute liver weights were diminished, but the relative liver weight was significantly increased in the 5 and 10 mg PFDoA/kg/day groups. Meanwhile, serum triglyceride (TG) concentrations were decreased significantly in rats dosed with 1 and 5 mg PFDoA/kg/day, while the liver lipid accumulation was observed in ultrastructure. The expression of peroxisome proliferator-activated receptor (PPAR)-α and its target genes, and to a lesser extent PPARγ, was induced by PFDoA. No significant changes in the expression of liver X receptor α (LXRα) or its target genes CYP7A1 and acetyl-CoA carboxylase 1 (ACC1) were noted, although the mRNA levels of several genes involved in lipogenesis and lipid transport were changed significantly in the certain of the experimental groups. In addition, superoxide dismutase (SOD) and catalase (CAT) activities were activated significantly in the 1 mg PFDoA/kg/day group and inhibited significantly with a concomitant increase of lipid peroxidation (LPO) levels in the 5 and 10 mg PFDoA/kg/day groups. Our results demonstrate that PFDoA exerts notable hepatotoxicity in male rats and that PPAR and its target genes, SOD and CAT activity, and LPO levels exhibited sensitivity to the toxicity of PFDoA.

Protective role of dimethyl diphenyl bicarboxylate (DDB) against erythromycin induced hepatotoxicity in male rats

In this study, dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB) was examined to justify its role in the hepatoprotection against erythromycin toxicity in male rats. Oral daily administration of toxic dose of erythromycin stearate (EE, 100 mg/kg body weight) was given to male rats for fourteen days to induce hepatotoxicity. It was found at the end of the experiment (14 days) that the total body weight was markedly decreased in rat treated with erythromycin stearate (EE). Hepatomegaly and splenomegaly were recorded in rats treated with erythromycin stearate (EE). The red blood cells (RBCs) count, haemoglobin content (Hb) and haematocrit value (Hct) were significantly reduced in rats treated with EE. The hepatotoxicities were monitored by increased level of plasma enzymes (aspartate aminotransferase; AST and alanine aminotransferase; ALT), total bilirubin, direct bilirubin, cholesterol, total lipids and glucose. The data obtained showed that oral administration of DDB (100 mg/kg body weight) has significantly prevented the occurrence of EE-induced liver damage. The biochemical data were supplemented by histopathological examination of the liver of control and treated rats. DDB showed a better hepatoprotective effect compared with ursodesoxycholic acid or Silymarin (Sil), as a reference drug.

Expression of adhesion molecules during cadmium hepatotoxicity

Inflammatory processes play a major role in the secondary injury of the liver produced by cadmium (Cd), and infiltration of neutrophils at the site of necrosis is a common observation. Although the infiltration of leukocytes (mainly neutrophils) into sites of injuried tissue within liver during Cd toxicity is mediated by adhesion molecules, little is known about expression of these adhesion molecules during Cd hepatotoxicity. In the present study, the expression of E-, P-selectin, intracellular adhesion molecule-1 (ICAM-1) and platelet-endothelial adhesion molecule-1 (PECAM-1) was analyzed by immunohistochemistry and immunofluoresence during Cd-induced hepatotoxicity in male rats. In contrast to E-, and P-selectin, ICAM-1 and PECAM-1 were constitutively expressed on sinusoidal endothelial cells of control liver. However, P-selectin was not induced within the liver by Cd administration, whereas E-selectin expression was induced in the liver with a marked increase in immunostaining on sinusoidal endothelial cells from 12 h to 7 days. Also, there was an upregulation in ICAM-1 immunostaining on sinusoidal endothelial cells from 12 h to 7 days after Cd administration, whereas there was no obvious change of PECAM-1 immunostaining on sinusoidal endothelial cells until 24 h. However, PECAM-1 expression was markedly decreased at 48 h but significantly increased at 7 days after Cd administration compared to control liver. Taken together, upregulation of E-selectin and ICAM-1 with biphasic changes in PECAM-1 expression within liver after Cd administration suggests an important role for these adhesion molecules during Cd hepatoxicity.

Heterogeneous Liver Lobe Responses of Carbon Tetrachloride-Induced Hepatotoxicity in Male Rats Pretreated with Hepatic Enzyme-Inducing Agents

The present study was designed to compare the susceptibility to carbon tetrachloride (CCl4)-induced hepatotoxicities of the different liver lobes of rats which had been subjected to pretreatment with phenobarbital sodium (PB) or β-naphthoflavone (BNF). A detailed investigation was done to determine whether the susceptibility to CCl4 hepatotoxicities was correlated with hepatic cytochrome P450 (CYP) activities in the different liver lobes. Male Wistar rats were given a single oral administration of CCl4 (0.1 mL/kg, dissolved in liquid paraffin) or vehicle alone following three daily intraperitoneal injections of PB (40 mg/kg, dissolved in sterile saline) or BNF (40 mg/kg, suspended in sesame oil). One day after the CCl4 administration, all animals were necropsied, and liver samples were obtained from the left and median lobes. Each sample was used for histopathological examination and 7-alkoxycoumarin O-dealkylase activity assay to evaluate the CYP activity. All the CCl4-treated animals revealed typical liver damage, such as the presence of ballooning degeneration and necrosis in centrilobular hepatocytes. PB pretreatment remarkably enhanced the extent of the liver damage, which was greater in the median lobe than the left lobe. BNF pretreatment only slightly enhanced the extent of the liver damage, which was also greater in the median lobe. These results indicate the different susceptibilities of rat liver lobes to CCl4-induced hepatotoxicities enhanced by pretreatment with PB or BNF. Moreover, the heterogeneity of the CYP activities enhanced by PB pretreatment was closely correlated with the susceptibility to CCl4-induced hepatotoxicities in the different liver lobes, although that by BNF pretreatment was not.