Acetaminophen-induced Hepatotoxicity In Rats Research Articles

Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats

Abstract This research aimed to explore the protective and therapeutic properties of safranal in mitigating inflammation and oxidative stress induced by elevated acetaminophen (APAP) doses in a rat model. The protective and therapeutic effects of safranal were determined by histopathologically and examining some biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), glutathione, glutathione peroxidase, catalase, malondialdehyde, interleukin-6, tumor necrosis factor-α, and interleukin-1β. Male Wistar–Albino rats were subject to random allocation, forming five groups, each comprising seven rats (n = 7) in the study. Group 1 was the control group. APAP was administered in Group 2 to induce hepatotoxicity. Rats in Groups 3, 4, and 5 received intraperitoneal injections of safranal at doses of 0.025, 0.05, and 0.1 mL/kg/day for 14 days, respectively. On the 15th day, to induce APAP-induced hepatotoxicity, four groups (Groups 2, 3, 4, and 5) acquired a single intraperitoneal injection of 600 mg/kg APAP. The presence of APAP-induced hepatotoxic effect was proven by elevated AST and ALT levels, which are typical biomarkers of liver function in addition to the demonstration of histopathological changes. The findings suggest that pre-treatment with safranal may offer a protective effect against hepatotoxicity by attenuating oxidative stress and the inflammatory response.

Safety and Hepatoprotective Assessments of Polyherbal Formulation in Lead and Acetaminophen-induced Hepatotoxicity in Rats

Safety and Hepatoprotective Assessments of Polyherbal Formulation in Lead and Acetaminophen-induced Hepatotoxicity in Rats

Galium aparine L. protects against acetaminophen-induced hepatotoxicity in rats

The toxicity of acetaminophen (N-acetyl-para-aminophenol (APAP)) is the most frequent cause of drug-induced liver damage. Galium aparine L. (GA) is traditionally used to treat jaundice. We aimed to investigate the hepatoprotective potential of GA in the APAP-induced hepatic encephalopathy (HE) rat model. Qualitative phytochemical characterization of GA was performed by LC/Q-TOF/MS analysis. Wistar rats were pretreated with GA (250 and 500 mg/kg b.wt. per oral) for five days. On the 6th day, the rats were exposed to APAP (1500 mg/kg b.wt. oral gavage) and behavioral tests (open field and passive avoidance tests) were applied on the 7th and 8th days. The animals were killed, and biochemical and histopathological parameters were assessed in blood and hepatic specimens. GA pretreated rats exhibited a significant reduction in APAP-induced liver damage, evidenced by the reduction in liver necrosis and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin (BIL). GA demonstrated an anxiolytic effect, as seen in the acquisition trial and grooming behavior. The short-term memory performances of animals were not changed in all groups, suggesting that APAP intoxication did not affect hippocampal function. These results show that GA extract markedly exerts hepatoprotective activity, while its effect on hepatic encephalopathy was limited.

The regenerative effect of stem cells on acetaminophen-induced hepatotoxicity in male albino rats

BackgroundAcetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. We aimed at studying the therapeutic potential of bone marrow mesenchymal stem cells (MSCs) in accelerating healing of acetaminophen-induced hepatotoxicity.ResultsThis prospective study included 50 male albino rats divided into 2 groups: hepatotoxic group and non-hepatotoxic group. Hepatotoxicity was induced in experimental rats by acetaminophen and then stem cells were transplanted into the rats and their effects on the liver cells were assessed. After injection of BM MSCs, the cells reached the targeted tissues. They were established in the central veins and blood sinusoids in the liver tissue. The hepatotoxic liver showed degeneration and loss of normal hepatic architecture as well as necrotic areas and congestion mainly in the portal tract vessels, dilation of blood sinusoids, and infiltration by inflammatory cells around the central veins. In addition, there were abnormal nuclei either irregular in shape or showing loss of open face compared to the normal control group. The liver tissue in BM MSC-treated group showed restoration of normal architecture of the liver tissue.ConclusionAdministration of MSCs has hepato-therapeutic effect on acetaminophen-induced hepatotoxicity in rats. The mechanism of this hepatoprotective effect may be through anti-inflammatory, anti-apoptotic, and immunomodulatory actions of MSCs.

Antioxidant and hepatoprotective potential of sweet basil (Ocimum basilicum L.) extract in acetaminophen-induced hepatotoxicity in rats

This research aimed to examine the effects of pre-treatment with basil extract, prepared as an infusion, on acetaminophen-induced acute liver injury in rats. In vitro analysis of total phenolic, flavonoid content, and antioxidant activity was performed by spectrophotometric methods. Effects of basil extract on oxidative stress parameters, biochemical markers of liver injury, and liver morphology were determined in an in vivo model of acetaminophen-induced liver injury in Wistar rats. Total phenolic content was 52.61 ± 1.35 mg GAE/g of DE, and flavonoid content was 0.5 ± 0.2 mg QE/g of DE. IC50 values ranged from 0.22 to 45.76 μg/ml for DPPH radical, OH radical, H2O2 and lipid peroxidation. Ascorbic acid was used as a positive control. The extract lowered the intensity of lipid peroxidation and potentiated the activity of antioxidant enzymes. In addition, serum levels of aspartate aminotransferase and alanine aminotransferase were significantly lower in basil extract-treated animals in comparison to respective controls.

Protective effect of Nectaroscordum tripedale extract and its bioactive component tetramethylpyrazine against acetaminophen-induced hepatotoxicity in rats

Hepatoxicity is a common complication of acetaminophen. This study was to evaluate the effects of Nectaroscordum tripedale extract (NTE) and its bioactive component tetramethylpyrazine (TMP) on acetaminophen-induced liver failure. The presence of TMP in NTE was determined by HPLC. The hepatoprotective effect of NTE and TMP (50, 100 and 200 mg/kg, respectively) was evaluated by the assay of liver function parameters; total bilirubin, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase activities (ALP) and superoxide dismutase (SOD). Results revealed that TMP was 1.24 mg/g in NTE. LD50 of the NTE and TMP was 3800 mg/kg and 2700 mg/kg, respectively. NTE and TMP (100 and 200 mg/kg) decreased the ALT, AST, ALP, and bilirubin but the SOD increased in a dose-dependent manner in acetaminophen-induced liver failure rats. In conclusion, NTE and its fraction TMP may be a protecting liver candidate against acetaminophen-induced hepatotoxicity.

Chrysin Effect in Prevention of Acetaminophen-Induced Hepatotoxicity in Rat.

Acetaminophen is a commonly used analgesic drug that induces hepatotoxicity at high doses and produces the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) through oxidase isoenzyme system. The antioxidant and anti-inflammatory activity of flavonoid chrysin has been reported in different studies. The present study was conducted to investigate the protective effect of chrysin on acute acetaminophen-induced hepatotoxicity. The cytotoxicity of chrysin on fibroblast cells was evaluated using MTT assay, and then, 54 rats were divided into nine groups of six, and acetaminophen (1500 mg/kg) was administered in all groups except for the control group, second and the seventh groups (40 mg/kg), and all groups were treated with chrysin for 14 days. Liver enzymes, inflammatory factors TNF-α and IL-2, and total antioxidant activity were measured in serum while liver tissue was histopathologically examined. Based on the MTT assay results, 31.25, 62.5, 125, 250, and 500 μg/mL chrysin had no adverse effects on healthy fibroblast cells (P < 0.05). Chrysin decreased the level of liver enzymes (ALT, AST, and ALP), which were previously increased after the use of acetaminophen (p < 0.05). The hepatoprotective effect and total antioxidant capacity increased in a dose-dependent manner and the effect of the highest concentration of chrysin was equal to the effect of silymarin (P < 0.05). TNF-α in groups 4 to 6 decreased in a dose-dependent manner (P = 0.04), and chrysin did not show any significant reducing effect on IL-2 compared to silymarin. Chrysin prevents the necrosis and injury of acute acetaminophen-induced hepatotoxicity by decreasing liver enzymes and TNF-α and increasing total antioxidant capacity and protecting the liver tissue.

Hepatoprotective and antioxidant activity of watercress extract on acetaminophen-induced hepatotoxicity in rats

IntroductionAcetaminophen (APAP) as an analgesic and antipyretic drug can result to liver damages while using more than 4 g/day. Therefore, APAP toxicity causes the liver to dysfunction. This study aims to investigate the hepatoprotective and antioxidant activity of hydroalcoholic extract of watercress (WC) in APAP-induced hepatotoxicity in rats. Materials and methodsRandomly, twenty-four Wistar rats were divided into four groups of six each. Groups named as control, APAP, APAP + WC and APAP + S for group 1, 2, 3, and 4, respectively. Group 1 received distilled water 1 ml/kg for 7 days. In group 2, 3, and 4, rats pretreated by receiving distilled water (1 ml/kg), WC extract (500 mg/kg), silymarin extract (mg/kg) for 7 days, respectively. Of note, to induce acute hepatotoxicity in groups 2, 3, and 4, rats posttreated by orally intoxicated with single dose of APAP (2 g/kg) on the sixth day. The animals were sacrificed on the seventh day. Alanine amino transferase (ALT), aspartate amino transferase (AST), ferric reducing ability of plasma (FRAP), protein carbonyl (PCO), total thiol (T-SH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were measured in plasma. It should be noted that the chemical composition of WC extract was identified by GC-MS analysis. ResultsThe results have shown that there was a significant increase in AST, ALT, FRAP and PCO content in APAP group in comparison to control. Also, there was a significant reduction in T-SH levels and GPx activity in APAP group compared to control. However, administration of WC extract and silymarin not only causes a significant decrease in AST activity, but they markedly increased T-SH content and GPx activity compared to APAP group. GC-MS analysis showed the major compositions were found to be benzenepropanenitrile (48.30 %), Phytol (10.10 %), α-cadinene (9.50%) and linolenic acid (8.0). ConclusionsIt is concluded that the WC extract reduces APAP-induced toxicity through its hepatoprotective and antioxidant activity in rats.

Amelioration of Acetaminophen-Induced Hepatotoxicity in Rat by Co-Administration of Quercetin and Resveratrol in Rats

Amelioration of Acetaminophen-Induced Hepatotoxicity in Rat by Co-Administration of Quercetin and Resveratrol in Rats

The Preventive Effects of Standardized Extract of Zataria multiflora and Carvacrol on Acetaminophen-Induced Hepatotoxicity in Rat: - Zataria multiflora and Carvacrol and Hepatotoxicity.

ObjectivesThe hepatotoxicity induced by Acetaminophen (AAP) mostly mediated by effect on oxidative stress parameters. The Zataria multiflora (Z.M) is an herbal medicine with well-known antioxidant effect. The aim of this study is investigation of preventive effects of Z.M and Carvacrol (CAR) on AAP-induced hepatotoxicity in rats.MethodsRats were randomly divided into four groups including: 1) Control, 2) Acetaminophen (AAP), 3) and 4) CAR. The saline, Z.M (200 mg/kg) and CAR (20 mg/kg) were administrated orally for 6 days, after that AAP (600 mg/kg) was administrated in the 7th day. Blood sampling was performed on the first and last days. Also, the liver tissue was removed for evaluation of Malondyaldehide (MDA), Thiol content, Superoxide dismutase (SOD) and Catalase (CAT). Total Protein (tPro), Glutamic Oxaloacetic Transaminase (GOT), Glutamic Pyruvic Transaminase (GPT) and Alkaline Phosphatase (ALP) in liver tissue were evaluated. The changes (Δ) of enzymes activities were presented.ResultsThe Δ GOT, Δ GPT and Δ ALP in CAR group significantly decreased compared to AAP group (P < 0.01 to P < 0.001) and Δ GPT in Z.M group was significantly reduced in comparison with AAP group (P < 0.05). Also, MDA, Thiol, SOD and CAT levels in treated groups were attenuated compared to AAP group (P < 0.05 to P < 0.001).ConclusionZ.M and CAR have a powerful hepatoprotective effect. CAR is more effective than Z.M. Based on the results. Z.M and CAR could be potent supplementary agents against hepatotoxicity of AAP in patients.

Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.

Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven-day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen-treated group compared with control, whereas concomitant administration of PYC in a dose of 50mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen-intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50mg/kg. Protective effect of PYC on acetaminophen-induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.

Antioxidative stress effects of vitamins C, E, and B12, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats.

BackgroundSeveral vitamins, including C, E, and B12, have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats.Materials and methodsAn in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT). The isolated hepatocytes were treated with vitamin C, vitamin E, vitamin B12 and their combination, with and without further addition of toxic concentrations of APAP. In addition, an in vivo experiment was carried out on Sprague Dawley rats treated intraperitoneally for 8 days with emulsions of the vitamins or their combination prior to injecting them with APAP.ResultsIn vitro results showed that vitamins C and B and the combination preparation significantly increased the percentage of hepatocyte mitochondrial activity, both with and without the addition of APAP (P<0.01). The mitochondrial activity in the isolated cultured hepatocytes was further enhanced with APAP addition. In vivo, the vitamins and their combination effectively reduced APAP-induced serum liver enzymes levels, namely ALT, AST, and ALP, and also attenuated oxidative stress and lipids peroxidation confirmed by the results of glutathione, superoxide dismutase, and maloondialdehyde.ConclusionPretreatment with vitamins C, E, B12, or their combination was found to be beneficial in preventing in vivo hepatic oxidative stress induced by APAP overdose. Vitamin C on its own showed superior protection against APAP-induced liver injury in rats compared to the other vitamins. The proliferation of APAP-intoxicated liver cells in vitro was highest when protected with the vitamins’ combination.

Acetaminophen-induced hepatotoxicity in rats is correlated with the accumulation of bile acids: an underlying mechanism

Acetaminophen-induced hepatotoxicity in rats is correlated with the accumulation of bile acids: an underlying mechanism

Resveratrol reduces light and electron microscopic changes in acetaminophen-induced hepatotoxicity in rats: Role of iNOS expression

ABSTRACTIntroduction: Hepatotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory properties. Objectives: In this study, the beneficial effects of RSV on APAP-induced hepatotoxicity was investigated in rats. Materials and methods: Group 1: Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000 mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP). The rats were sacrificed 24 h after administration of APAP. Light and electron microscopic changes were evaluated. Levels of malondialdehyde (MDA) and glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were determined in liver tissue. Results: Rats of the ethanol, saline, and RSV groups did not present any histopathological alterations. In the APAP group, we observed vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of glycogen content. In the APAP+RSV group, these changes were markedly reduced. iNOS immunostaining showed very weak positive stained hepatocytes the sections of control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group, intensity of iNOS immunostaining decreased. A significant increase in MDA and decreases in GSH level, CAT, and SOD activity indicated that APAP-induced hepatotoxicity was mediated through oxidative stress. Significant beneficial changes were noted in tissue oxidative stress indicators in rats treated with RSV. Conclusion: These biochemical, histopathological, and ultrastructural findings revealed that RSV reduced the severity of APAP-induced alterations in liver.

Hepatoprotective Potential of Green Tea Extract against Experimental Hepatotoxicity in Rats

An experimental study was conducted to evaluate the hepatoprotective effect of aqueous extract of Camellia sinensis or green tea extract and N-acetyl-L-cysteine in acetaminophen-induced hepatotoxicity in rats. Male Wistar rats (n=24) of 3 mon age were equally divided into 4 groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with oral administration of 500 mg/kg of acetaminophen from day 1 to day 3. Groups 2, 3 and 4 were subsequently administered orally with distilled water, 300 mg/kg of N-acetyl-L-cysteine and 100 mg/kg green tea extract, respectively for 11 days. Mean body weights and biomarkers of hepatotoxicity were estimated on days 0, 4 (confirmation of toxicity) 15 (at the end of treatment). Hematological parameters were evaluated on 4 and 15 d. Antioxidant profile and ATPase enzymes were assessed at the end of the experiment. Livers were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. Antioxidant profile, ATPase, hematological and serobiochemical parameters were significantly altered and histopathological changes were noticed in liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with N-acetyl-L-cysteine and green tea extract, respectively. The results of the present investigation enunciated that green tea extract has potent hepatoprotective activity, though N-acetyl-L-cysteine was found superior in restoring the pathological alterations in acetaminophen-induced hepatotoxicity in Wistar rats.

Protective activity of an anthocyanin-rich extract from bilberries and blackcurrants on acute acetaminophen-induced hepatotoxicity in rats

Acetaminophen (N-acetyl-p-aminophenol, APAP) overdosage can produce fatal centrilobular hepatic necrosis in humans. The present study attempted to investigate the protective effect of an anthocyanin-rich extract from bilberries and blackcurrants (AE) against APAP-induced acute hepatic damage in rats. Treatment with AE normalised blood activities of glutamate oxaloacetate and glutamate pyruvate transaminase and prevented APAP-induced plasmatic and tissutal alterations in biomarkers of oxidative stress, probably due to various bioproperties of the components of the extract.

Assessment of Organ Damage Markers in Acetaminophen-induced Hepatotoxicity in Rats Pre-treated with Quail Eggs

Assessment of Organ Damage Markers in Acetaminophen-induced Hepatotoxicity in Rats Pre-treated with Quail Eggs

Effect of Quail Egg Pretreatment on the Lipid Profile and Histomorphology of the Liver of Acetaminophen-Induced Hepatotoxicity in Rats

Quail eggs contain lots of vitamins and minerals that help fight some diseases in the body. Overdose of paracetamol® (acetaminophen) is considered one of the major causes of damages to liver cells. This study was conducted to assess the effect of graded doses of quail egg pretreatment on lipid profile and liver histomorphology of acetaminophen-induced hepatotoxicity in rats. Thirty (30) albino rats were assigned into 5 groups of 6 rats per group. Rats in groups 2-4 were pretreated with 30 mg/kg, 15 mg/kg, 7.5 mg/kg respectively of quail egg solution for 7 days before intoxication with 2000 mg/kg paracetamol® orally. Rats in group 5 were intoxicated but pretreated with distilled water (DW) at 10 ml/kg to serve as negative control while rats in group 1 were not intoxicated but pretreated with DW (10 ml/kg) (positive control). Fourty eight (48 h) hours post intoxication, blood was collected for lipid profile analysis. Thereafter, 2 rats per group were humanely sacrificed and the liver collected for histomorphological examination. The results obtained showed that 30 mg/kg quail egg-pretreated rats (Group 2 rats) had significantly (P

Therapeutic potential of alpha-ketoglutarate against acetaminophen-induced hepatotoxicity in rats.

Objective:Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats.Materials and Methods:Animals were divided into three groups of six animals each. Group I (Vehicle control): Normal Saline, Group II (APAP): A single intraperitoneal injection of 0.6 g/kg, Group III (APAP + α-KG): APAP as in Group II with α-KG treatment at a dose of 2 g/kg, orally for 5 days. Then the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) with oxidative stress markers including malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and histopathology were analyzed.Results:The results indicate that APAP caused significant elevations in ALT, AST, ALP, and MDA levels, while GSH, SOD, and CAT were significantly depleted while co-administration of α-KG showed a significant (P < 0.05) reduction in the severity of these damages. Histologically, the liver showed inflammation and necrosis after APAP treatment, which were significantly restored with co-administration of α-KG.Conclusion:These results indicate the possible therapeutic potential of α-KG in protecting liver damage by APAP in rats.

Modulatory potentials of aqueous leaf and unripe fruit extracts of Carica papaya Linn. (Caricaceae) against carbon tetrachloride and acetaminophen-induced hepatotoxicity in rats.

Introduction:Carica papaya Linn is used in a traditional medicine for hepatobiliary disorders. This study investigated the hepatomodulatory effects of aqueous extracts of C. papaya leaf (CPL) and unripe fruit (CPF) at doses of 100 and 300 mg/kg on carbon tetrachloride (CCl4) and acetaminophen (ACM)-induced liver toxicities in rats.Materials and Methods:Rats were administered CCl4 (3 ml/kg in olive oil, i.p.) followed by oral administration of CPL and CPF at 2, 6 and 10 h intervals. The ACM model proceeded with the same method but inclusive of animals treated with N-acetyl cysteine (3 ml/kg i.p). At the end of the study, serum levels of liver biomarkers and antioxidant enzymes were assessed and histology of the liver tissues determined.Results:There was a significant (P < 0.05) reduction in CCl4 and ACM-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and direct bilirubin at 100 and 300 mg/kg, respectively. The levels of catalase (CAT), superoxide dismutase and reduced GSH were decreased in both models with corresponding significantly (P < 0.05) elevated level of malondialdehyde. However, these antioxidant enzymes were significantly (P < 0.05) increased in CPL and CPF-treated rats. Histopathological assessment of the liver confirmed the protective effects of CPL and CPF on CCl4 and ACM-induced hepatic damage evidenced by the normal presentation of liver tissue architecture.Conclusion:These results indicate that aqueous extracts of C. papaya may be useful in preventing CCl4 and ACM-induced liver toxicities.