Acetaminophen-induced Hepatotoxicity In Rats Research Articles

Short day photoperiod protects against acetaminophen-induced heptotoxicity in rats

This study investigated the effect of different photoperiods on acetaminophen-induced hepatotoxicity in rats. Twenty four adult male rats (average weight = 160±7g) were conditioned to different photoperiod regimens for 6 weeks. At the end of the 6-week period, rats exposed to normal, short and long photoperiods received oral acetaminophen (2g/kg body weight) while in the control group, exposed to normal photoperiod, received oral saline. Rats were sacrificed 24 h after acetaminophen administration by cervical dislocation and blood was collected by cardiac puncture for the estimation of liver enzymes activities. Liver tissues were excised and homogenized for estimation of liver malondialdehyde (MDA) concentration. Elevation of serum levels of alanine and aspartate transaminases and alkaline phosphatase caused by acetaminophen intoxication were not affected in rats subjected to long photoperiod while these parameters were significantly (P<0.05) reduced in rats subjected to short photoperiod. However, alteration of photoperiod resulted in significantly (P<0.05) lower serum gamma glutamate transpeptidase and total protein in acetaminophentreated rats. All groups of rats had similar serum albumin while serum malondialdehyde concentration was significantly lower in rats subjected to short photoperiod. This study revealed the protective effects of short photoperiod against acetaminophen-induced hepatotoxicity and lipid peroxidation in rats. Key words : Acetaminophen, photoperiod, lipid peroxidation, Hepatotoxicity

Effect of amlodipine, lisinopril and allopurinol on acetaminophen-induced hepatotoxicity in rats

BackgroundExposure to chemotherapeutic agents such as acetaminophen may lead to serious liver injury. Calcium deregulation, angiotensin II production and xanthine oxidase activity are suggested to play mechanistic roles in such injury. ObjectiveThis study evaluates the possible protective effects of the calcium channel blocker amlodipine, the angiotensin converting enzyme inhibitor lisinopril, and the xanthine oxidase inhibitor allopurinol against experimental acetaminophen-induced hepatotoxicity, aiming to understand its underlying hepatotoxic mechanisms. Material and methodsAnimals were allocated into a normal control group, a acetaminophen hepatotoxicity control group (receiving a single oral dose of acetaminophen; 750mg/kg/day), and four treatment groups receive N-acetylcysteine (300mg/kg/day; a reference standard), amlodipine (10mg/kg/day), lisinopril (20mg/kg/day) and allopurinol (50mg/kg/day) orally for 14 consecutive days prior to acetaminophen administration. Evaluation of hepatotoxicity was performed by the assessment of hepatocyte integrity markers (serum transaminases), oxidative stress markers (hepatic malondialdehyde, glutathione and catalase), and inflammatory markers (hepatic myeloperoxidase and nitrate/nitrite), in addition to a histopathological study. ResultsRats pre-treated with amlodipine, lisinopril or allopurinol showed significantly lower serum transaminases, significantly lower hepatic malondialdehyde, myeloperoxidase and nitrate/nitrite, as well as significantly higher hepatic glutathione and catalase levels, compared with acetaminophen control rats. Serum transaminases were normalized in the lisinopril treatment group, while hepatic myeloperoxidase was normalized in the all treatment groups. Histopathological evaluation strongly supported the results of biochemical estimations. ConclusionAmlodipine, lisinopril or allopurinol can protect against acetaminophen-induced hepatotoxicity, showing mechanistic roles of calcium channels, angiotensin converting enzyme and xanthine oxidase enzyme in the pathogenesis of hepatotoxicity induced by acetaminophen.

Combined administration of silymarin and vitamin C stalls acetaminophen-mediated hepatic oxidative insults in Wistar rats

Oxidative insult by free radicals has been implicated in drug-induced hepatic damage and this has resulted in frequent episodes of liver disorders. Therapeutic efficacy of antioxidants may provide a possible solution to this menace. This study was carried out to investigate the effect of combined administration of silymarin and vitamin C in rescuing acetaminophen-induced hepatotoxicity in rats. Hepatotoxic rats were orally administered with silymarin and vitamin C at 100 and 200mg/kg body weight, respectively. At the end of the experiment, liver function indices, antioxidant parameters and histological analysis were evaluated. We observed that the significantly increased (p<0.05) activities of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, as well as levels of thiobarbituric acid reactive substances and serum total bilirubin, were markedly reduced following co-administration of silymarin and vitamin C. The compounds also effectively reversed the reduced activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase and total protein concentration in the hepatotoxic rats. These findings are indicative of hepatoprotective and antioxidant attributes of the two compounds which are also supported by the histological analysis. The available evidences in this study suggest that the complementary effects of silymarin and vitamin C proved to be capable of ameliorating acetaminophen-mediated hepatic oxidative damage and the probable mechanism is via antioxidative action.

Hepatoprotective and antioxidant activity of Leea asiatica leaves against acetaminophen-induced hepatotoxicity in rats

Leea asiatica (L.) Ridsdale, a folk medicinal plant is used by the ethnic people of North East India for the treatment of hepatic disorder. In this study, we have investigated the hepatoprotective and antioxidant activity of L. asiatica leaves against acetaminophen induced hepatotoxicity. Methanol extract of L. asiatica (150 and 300 ㎎/㎏/day, p.o.) were administered to rats for three consecutive days followed by single acetaminophen (3000 ㎎/㎏, p.o.) administration on 3rd day. After 48 h of acetaminophen administration animals were sacrificed and biochemical estimation of serum, in vivo antioxidant activity using liver tissue were carried out. High levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum alkaline phosphatase, total bilirubin, direct bilirubin, total cholesterol and triglycerides were observed in disease control group, which found near to normal in extract treated groups. Higher dose exhibited significant hepatoprotective activity against acetaminophen induced toxicity. Level of superoxide dismutase, catalase, glutathione peroxidase in liver tissue, and reduced glutathione in liver and blood were also significantly increased in extract (300 ㎎/㎏) treated animals compare to disease control group. In this study we found that leaves of L. asiatica exhibited potent hepatoprotective activity against acetaminophen induced hepatic damage in experimental animals which justify the folklore claim, and the possible mechanism of this activity may be due to strong antioxidant activities of extract.

Protective effect of pioglitazone, a PPARγ agonist against acetaminophen-induced hepatotoxicity in rats.

Acetaminophen has a reasonable safety profile when consumed in therapeutic doses. However, it could induce hepatotoxicity and even acute liver failure when taken at an overdose. Pioglitazone, PPARγ ligand, is clinically tested and used in treatment of diabetes. PPARγ is a key nuclear hormone receptor of lipid metabolisms and regulates several gene transcriptions associated with differentiation, growth arrest, and apoptosis. The aim of our study was to evaluate the hepatoprotective activity of pioglitazone on acetaminophen-induced hepatotoxicity and to understand the relationship between the PPARγ and acetaminophen-induced hepato injury. For the experiment, Sprague-Dawley rats (160-180 g) were used and divided into four groups. Groups I and II were normal and experimental controls, respectively. Groups III and IV received the pioglitazone 20 mg/kg for 10 days. Hepatotoxicity was induced in Groups II and III on the eighth day with acetaminophen (i.p. 350 mg/kg body weight). The hepatoprotective effect was evaluated by performing an assay of the total protein, total bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, and α-fetoprotein as well as glutathione peroxidase, lipid peroxidation, catalase, superoxide dismutase, and glutathione transferase and liver histopathology. The assay results were presented as mean and standard error of mean for each group. The study group was compared with the control group by one-way ANOVA test. A p value of <0.05 was considered significant. Pioglitazone significantly reduced the elevated level of above serum marker enzymes and also inhibits the free radical formation by scavenging hydroxyl ions. It also restored the level of LPO and significantly elevated the levels of endogenous antioxidant enzymes in acetaminophen-challenged hepatotoxicity. Liver histopathological examination showed that pioglitazone administration antagonized acetaminophen -induced liver pathological damage. Various biochemical estimations of different hepatic markers and antioxidant enzymes and histopathological studies of liver tissues glimpse a support to its significant hepatoprotective activity on acetaminophen -induced hepatotoxicity.

Hepatoprotective Action of Echinophora platyloba DC Leaves Against Acute Toxicity of Acetaminophen in Rats

ABSTRACTContext: Acetaminophen, an analgesic and antipyretic drug, causes fulminant hepatic injury at high doses. Objective: This study evaluated the effects of Echinophora platyloba extract on acetaminophen-induced hepatotoxicity in rats. Materials and methods: Forty-eight rats were divided into six groups. The first (control) and second (test without treatment) groups were administered the solvent of the drug in the morning (08:00) and evening (16:00) on days 1 and 2 but, the third, fourth, and fifth groups received 200, 500, and 1,000 mg/kg b.w E. platyloba extract by gavage on the same days, respectively. The sixth group (positive control) received 200 mg/kg b.w silymarin. Then all groups, except the control group, received 400 mg/kg acetaminophen by gavage on day 2 (10:00). After 24 hr, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), malondialdehyde (MDA), and antioxidant capacity plus liver catalase (CAT) activity and histopathological studies were determined. Data were analyzed with one-way analysis of variance (ANOVA). Results: Treatment of rats with different doses of E. platyloba extract significantly reduced (p < .05) the elevated serum levels of ALT, AST, ALP, and MDA compared to the untreated group. The effects of 1,000 mg/kg E. platyloba were similar to the control and treated silymarin groups. Moreover, E. platyloba significantly increased the activity of liver CAT and serum antioxidant capacity at different doses. Also, E. platyloba extract improved liver histopathological changes compared with the respective control group. Conclusion: The results suggest that E. platyloba extract has impressive hepatoprotective effects on acute acetaminophen-induced liver injuries.

Thymoquinone treatment against acetaminophen-induced hepatotoxicity in rats

AimIn this study, we aimed to examine the efficacy of thymoquinone (TQ) treatment in acetaminophen-induced liver toxicity in rats. MethodsForty Wistar Albino rats were used for the study (four groups, with 10 rats for each group). Animals in the control group were not given any medication. In the thymoquinone (TQ) group, animals were given three times 5 mg/kg oral thymoquinone for every six hours, which equals to a total dose of 15 mg/kg. In the acetaminophen (APAP) group, animals were given APAP at a single dose of 500 mg/kg orally. In the APAP + TQ group, animals were given 500 mg/kg APAP orally followed by three doses of TQ at a 15 mg/kg total dose in an 18-h time interval. All animals were sacrificed at the 24th hour. Alanine amino transferase (ALT), aspartat amino transferase (AST), superoxide dismutase (SOD), oxidized glutathione (GSSG), glutathione peroxides (GSH-Px), and malondialdehyde (MDA) activities were measured in rat blood. Histopathological examination was also performed. ResultsSerum ALT, AST levels, GSSG, and SOD activity as well as the serum and tissue MDA levels were found to be higher in the APAP group than in the control group (p ≤ 0.001). Likewise, serum GSH-Px activity was found to be lower in the APAP group (p ≤ 0.001). In contrast, in the APAP + TQ group, serum ALT, AST levels, GSSG, SOD activity and the serum and tissue MDA levels were found to be lower compared to that of the APAP group. This difference was statistically significant (p ≤ 0.001). In the APAP + TQ group, the GSH-Px activity was found to be significantly higher compared to the APAP group (p < 0.05). In contrast to this finding, the GSH-Px activity in the APAP + TQ group was found to be lower than that of the control group (p ≤ 0.001). Histopathological analysis revealed significant liver necrosis and toxicity with a high dose of APAP where TQ treatment was related with significantly lower liver injury scores. ConclusionTQ treatment may have an important therapeuthic effect via the upregulation of antioxidant systems in the APAP-induced liver hepatotoxicity in rats.

Antihepatotoxic activity of a quantified Desmodium adscendens decoction and d-pinitol against chemically-induced liver damage in rats

Ethnopharmacological relevanceThe isolation of d-pinitol (or 3-O-methyl-d-chiro-inositol) from an aqueous decoction of Desmodium adscendens (Fabaceae) leaves and twigs is reported. The protective and curative effect of this decoction, in which d-pinitol was quantified, and of pure d-pinitol, against chemically-induced liver damage in rats has been evaluated. Materials and methodsEnzyme levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP), which are among the usual biomarkers for liver damage, were determined in serum samples of experimental animals. The protective effects against d-galactosamine-induced and ethanol-induced liver damage of a decoction of D. adscendens, quantified on its main constituent d-pinitol, was investigated in rats. In addition, the curative effects of pure d-pinitol and D. adscendens against chronic d-galactosamine-induced and acute acetaminophen-induced hepatotoxicity in rats was studied. Silymarin was used as positive control. ResultsIn a first experiment evaluating the protective effect against acute d-galactosamine-induced liver damage in rats, a significant decrease of AST and ALT was observed for the D. adscendens decoction at a dose equivalent to 5mg/kg/day and 20mg/kg/day d-pinitol, as well as 20mg/kg/day pure d-pinitol. With respect to chronic ethanol-induced liver damage in rats, the protective effects of D. adscendens at doses equivalent to 2mg/kg/day and 10mg/kg/day d-pinitol, were not observed for serum AST and ALT levels. However, with respect to reduced mortality of animals, statistical analysis showed a trend towards significance for the Desmodium group receiving a dose equivalent to 10mg/kg/day d-pinitol, versus the untreated hepatotoxic animals. Additional experiments in rat models of acute acetaminophen-induced and chronic d-galactosamine-induced liver damage indicated that D. adscendens decoction and pure d-pinitol had no curative effect when given in a dose equivalent to 10mg/kg/day d-pinitol, or up to 20mg/kg/day as a pure compound daily, respectively. ConclusionsThe aqueous decoction of D. adscendens showed a protective effect in rats against liver damage induced by d-galactosamine and ethanol, and this effect is at least in part due to the presence of d-pinitol. However, no curative effect of D. adscendens decoction or d-pinitol on liver damage induced by the tested chemicals could be demonstrated.

Hepatoprotective and In vivo Anti-oxidant Activity of Costus afer Leaf Extracts against Acetaminophen-Induced Hepatotoxicity in Rats

This study investigated the hepatoprotective and in vivo antioxidant activity of orally administered chloroform and ethanol Costus afer leaf extracts (20 - 60 mg/kg b.w.) on 1 g/kg b.w. acetaminophen-induced acute hepatic injury in albino rats for 7 days. Result showed no significant difference in plasma and hepatic superoxide activities. Plasma catalase (CAT) activity was significantly reduced in 20 and 40 mg/kg chloroform extracts and 20 mg/kg ethanol extract treated groups. Hepatic CAT activity was reduced significantly at co-administered 20 mg/kg ethanol extract and 1 g/kg ACT treated group. Plasma and hepatic glutathione levels were elevated significantly in chloroform and ethanol leaf extracts treated groups. The plasma and liver glutathione S-transferase activity in the chloroform extract groups were significantly reduced while ethanol leaf extract showed no significant difference. The plasma and hepatic MDA concentrations in the chloroform and ethanol extracts treated groups were found reduced. Further studies showed that the reduction in AST and ALT elevated activities induced by ACT was more profound in ethanol treated groups than chloroform treated groups. Therefore, findings from this present study indicate that the chloroform leaf extract possess high antioxidant effect than ethanol leaf extracts while ethanol leaf extract possess high hepatoprotective potentials than chloroform leaf extract.

Therapeutic potential of Moringa oleifera extracts against acetaminophen-induced hepatotoxicity in rats

Context: Moringa oleifera Lam. (Moringaceae) is a rich source of essential minerals and antioxidants; it has been used in human and animal nutrition. The leaves and flowers are being used by the population with great dietary importance.Objective: The present study was to investigate the therapeutic effects of the hydroethanolic extract of Moringa oleifera (MO) leaves and flowers against hepatotoxicity induced by acetaminophen (APAP) in rats.Materials and methods: In the hepatoprotective study, either flowers or leaves of hydroethanolic extract (200 or 400 mg/kg bw through IP injection) were administered an hour after APAP administration. N-Acetylcysteine (NAC) was used as the positive control for this study. Liver and kidney function tests including lipid peroxidation levels were analyzed and histopathological changes of liver and kidney were also observed.Results: Acetaminophen-induced hepatotoxicity increased the activities of liver marker enzymes. Histologically, the liver was observed to have inflammation and bridging necrosis. Liver marker enzymes were significantly reduced when treated with flower and leaf extracts of MO in animals with APAP induced toxicity. In addition, there were no significant changes observed in clinical markers of kidney function. Histological observation on liver tissue from the rats treated with MO flower and leaf extract showed reduction in the severity of the liver damage.Discussion and conclusion: These results indicated the possible therapeutic action of flower and leaf extract from MO in protecting liver damage in rats given an over dosage of APAP.

Effect of S-methylisothiourea in acetaminophen-induced hepatotoxicity in rat

Nitric oxide synthesized from inducible nitric oxide synthase (iNOS) plays role in acetaminophen (APAP)-induced liver damage. The present study was undertaken to evaluate the effect of iNOS inhibitor S-methylisothiourea (SMT) in APAP-induced hepatotoxicity in rats (1g/kg, i.p.). SMT was (10, 30, and 100mg/kg; i.p.) given 30min before and 3h after APAP administration. At 6 and 24h, blood was collected to measure alanine transaminase (ALT), aspartate transaminase (AST), and nitrate plus nitrite (NOx) levels in serum. At 48h, animals were sacrificed, and blood and liver tissues were collected for biochemical estimation. SMT reduced significantly the serum ALT, AST, and NOx levels at 24 and 48h and liver NOx levels at 48h as compared with APAP-treated control. The amount of peroxynitrite measured by rhodamine assay was significantly reduced by SMT, as compared with APAP-treated control group. SMT treatment (30mg/kg) has significantly reduced the lipid peroxidation and protein carbonyl levels, increased SOD and catalase, and reduced glutathione and total thiol levels significantly as compared with APAP-treated control. SMT 30mg/kg dose has protected animals from APAP-induced hypotension and reduced iNOS gene expression. Hepatocytes were isolated from animals, and effect of SMT on apoptosis, MTP, and ROS generation was studied, and their increased value in APAP intoxicated group was found to be significantly decreased by SMT (30mg/kg) at 24 and 48h. In conclusion, nitric oxide produced from iNOS plays important role in toxicity at late hours (24 to 48h), and SMT inhibits iNOS and reduces oxidative and nitrosative stress.

Hepatoprotective and antioxidant effects of Monochoria vaginalis against acetaminophen-induced hepatotoxicity in rats

The present study was aimed to investigate the hepatoprotective and antioxidant activities of ethanol extract from Monochoria vaginalis (250 mg/kg and 500 mg/kg B/W) on acetaminophen (APAP) induced rat hepatic injury. Monochoria vaginalis is a traditional medicinal plant that is commonly used to treat and improve liver conditions in India and other Asian countries. The development of hepatotoxicity induced by APAP is promoted by oxidative stress. APAP treated group significantly (P < 0.01) elevated the serum enzymatic levels like glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, alkaline phosphatase (SALP), total bilirubin and malondialdehyde (MDA), which were restored towards normalization significantly (P < 0.01) thanol extract of yonochoria vagin is (EEMV). In addition, the EEMV significantly (P < 0.01) elevated the decreased level of total protein and antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione-s-transferase and reduced glutathione. Apart from these, histopathological changes also showed the protective nature of the EEMV against APAP induced hepatic damage in liver tissues. The activity of EEMV at 500 mg/kg B/W was comparable to the standard drug silymarin (25 mg/kg B/W). In conclusion, these data suggest that the EEMV possess hepatoprotective and antioxidant effects against APAP-induced hepatotoxicity and oxidative stress in rats.

Knockdown of superoxide dismutase 2 enhances acetaminophen-induced hepatotoxicity in rat

Drug-induced hepatotoxicity is a major problem in drug development, and oxidative stress is known as one of the causes. Superoxide dismutases (SODs) are important antioxidant enzymes against reactive oxygen species (ROS). Mitochondria are the major source of superoxide production, and SOD2 is mainly localized in mitochondria and, with other SODs, plays an important role in scavenging superoxide. Previously, we reported the establishment of an adenovirus vector with short hairpin RNA against rat SOD2 (AdSOD2-shRNA), and applied this to evaluate drug-induced cytotoxicity. In this study, infection of AdSOD2-shRNA to Fisher 344 rats resulted in a significant decrease of SOD2 mRNA, protein expression, and SOD2 enzyme activity to 28%, 35%, and 39%, respectively, 7 days after infection. Serum AST and ALT were significantly increased by single oral administration of acetaminophen (1000 mg/kg) to these SOD2-knockdown rats without fasting compared with the control adenovirus infected groups. Heme oxygenase-1 protein, known to be induced by oxidative stress, was detected in SOD2-knockdown rats administered acetaminophen. In addition, protein carbonyl and lipid peroxidation, also known to be induced by oxidative stress, were significantly increased in SOD2 knockdown rats. This is the first report of a SOD2-knockdown rat model that could be useful to evaluate the drug-induced hepatotoxicity with high sensitivity.

Hepatoprotective and Antioxidant Effect of Andrographis echioides N. against Acetaminophen Induced Hepatotoxicity in Rats

Hepatoprotective and Antioxidant Effect of Andrographis echioides N. against Acetaminophen Induced Hepatotoxicity in Rats

Studies on preventive effects of diphenyl diselenide on acetaminophen-induced hepatotoxicity in rats

Organoselenium are compounds with important antioxidant activity and with many biological activities interesting from pharmacological point of view. The aim of this study was to evaluate the protective effect of diphenyl diselenide (PhSe) 2 on hepatotoxicity caused by administration of acetaminophen (AA) in rats. Rats received (PhSe) 2 orally (31 mg/kg, dissolved in canola oil) for 2 days. After the second day of treatment, rats received AA orally (2 g/kg) in unique dose. Twenty-four hours after the last administration of AA, plasma was used for biochemical assays aspartate (AST) and alanine aminotransferases (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), γ-glutamyl transferase (γ-GT) activities. Glutathione- S-transferase (GST), δ-aminolevulinic dehydratase (δ-ALA-D) and catalase activities as well as ascorbic acid and TBARS levels were determined in the liver of rats. (PhSe) 2 protected against the increase in AST, ALT, ALP, LDH and γ-GT activities induced by AA exposure to rats. The histological data showed that sections of liver from AA-exposed rats presented intense cellular necrosis, characterized by the presence of Kupffer cells and other infiltrating cells, mainly around of the centrilobular vein. (PhSe) 2 significantly attenuated AA-induced hepatic histopathological alterations. Administration of (PhSe) 2 protected against the increase in TBARS levels and the decrease in δ-ALA-D and GST activities as well as ascorbic acid content induced by AA exposure in rats. Catalase activity remained unaltered in all treated groups. The protective effect of (PhSe) 2 against hepatotoxicity caused by AA exposure in rats was demonstrated.

Effects of Erdosteine on Acetaminophen-induced Hepatotoxicity in Rats

We investigated the effects of erdosteine on acetaminophen (APAP)-induced hepatotoxicity in rats. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), AST (aspartate aminotransferase), and ALT (alanine transaminase) activities, and malonyldialdehyde (MDA) and nitric oxide levels as oxidant/antioxidant biochemical parameters were investigated with light microscopic evaluation in adult female Wistar Albino rats. APAP administration produced a decrease in hepatic SOD, CAT, and GSH-Px activities, and coadministration of erdosteine (150 and 300 mg/kg) resulted in increases in the activities. MDA and NO levels increased in the APAP group, and erdosteine treatments prevented these increases. Significant elevations in serum AST and ALT levels were observed in the APAP group, and when erdosteine and APAP were coadministered, their serum levels were close to those in the control group. Light microscopic evaluation of livers showed that there were remarkable centrilobular (zone III) hepatic necrosis and mild to moderate sinusoidal congestion in the APAP group, whereas in the erdosteine group, cellular necrosis was minimal and the hepatocytes maintained a better morphology when compared to the APAP group. Erdosteine prevented APAP-induced liver injury and toxic side effects probably through the antioxidant and radical scavenging effects of erdosteine.

Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats

Cuscuta chinensis is a commonly used traditional Chinese medicine to nourish the liver and kidney. Due to the poor water solubility of its major constituents such as flavonoids and lignans, its absorption upon oral administration could be limited. The purpose of the present study was to use the nanosuspension method to prepare C. chinensis nanoparticles (CN), and to compare the hepatoprotective and antioxidant effects of C. chinensis ethanolic extract (CE) and CN on acetaminophen-induced hepatotoxicity in rats. An oral dose of CE at 125 and 250mg/kg and CN at 25 and 50mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. These biochemical assessments were supported by rat hepatic biopsy examinations. In addition, the antioxidant activities of CE and CN both significantly increased superoxide dismutase, catalase, glutathione peroxidase, and reduced malondialdehyde (P<0.05). Moreover, the results also indicated that the hepatoprotective and antioxidant effects of 50mg/kg CN was effectively better than 125mg/kg CE (P<0.05), and an oral dose of CN that is five times as less as CE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other water poorly soluble herbal medicines and furthermore to decrease the treatment dosage.

Hepatoprotective and antioxidant effects of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats

Tu-Si-Zi, the seeds of Cuscuta chinensis Lam. (Convolvulaceae), is a traditional Chinese medicine that is commonly used to nourish and improve the liver and kidney conditions in China and other Asian countries. As oxidative stress promotes the development of acetaminophen (APAP)-induced hepatotoxicity, the aim of the present study was to evaluate and compare the hepatoprotective effect and antioxidant activities of the aqueous and ethanolic extracts of C chinensis on APAP-induced hepatotoxicity in rats. The C chinensis ethanolic extract at an oral dose of both 125 and 250 mg/kg showed a significant hepatoprotective effect relatively to the same extent ( P < 0.05) by reducing levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), and alkaline phosphatase (ALP). In addition, the same ethanolic extract prevented the hepatotoxicity induced by APAP-intoxicated treatment as observed when assessing the liver histopathology. Regarding the antioxidant activity, C chinensis ethanolic extract exhibited a significant effect ( P < 0.05) by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and by reducing malondialdehyde (MDA) levels. In contrast, the same doses of the aqueous extract of C chinensis did not present any hepatoprotective effect as seen in the ethanolic extract, and resulted in further liver deterioration. In conclusion, these data suggest that the ethanolic extract of Cuscuta chinensis can prevent hepatic injuries from APAP-induced hepatotoxicity in rats and this is likely mediated through its antioxidant activities.

Evaluation of the hepatoprotective effect of Ocimum lamiifolium methanolic extract on acetaminophen-induced hepatotoxicity in rats – precision cut liver slices

Evaluation of the hepatoprotective effect of Ocimum lamiifolium methanolic extract on acetaminophen-induced hepatotoxicity in rats – precision cut liver slices

キャピラリー電気泳動・質量分析計（CE/MS）を用いたacetaminophen誘発ラット肝毒性に関するメタボノミクス検討

キャピラリー電気泳動・質量分析計（CE/MS）を用いたacetaminophen誘発ラット肝毒性に関するメタボノミクス検討