Acetaminophen-induced Hepatic Damage Research Articles

Jasminum elongatum Ameliorates Acetaminophen Induced Hepatotoxicity by Modulating Dysregulated Antioxidant Enzyme System

Objectives To evaluate the hepatoprotective activity of fractions of Jasminum elongatum methanolic extract against acetaminophen-induced hepatic damage. Materials and Methods Fractions obtained from methanolic extract of J. elongatum (petroleum ether, chloroform and hydroalcoholic) were investigated for hepatoprotective activity. Doses of 100 mg/kg and 200 mg/kg of different fractions were administered for 7 days, and acetaminophen toxicity was induced on the eighth day. After 24 hr of toxicity induction, biochemical markers and histological alterations were measured to determine the amount of hepatoprotection. Results The chloroform and hydroalcoholic fractions showed a significant decrease in biochemical parameters when compared to the toxic group, which was confirmed by histopathological changes and antioxidant parameters. Conclusion The results of this study revealed that the chloroform and hydroalcoholic fraction of J. elongatum have significant hepatoprotective activity against acetaminophen-induced toxicity.

Hepatoprotective Potential of Malabar Tamarind (Garcinia gummi-gutta) Fruit-Rind Extract in Acetaminophen-Induced Toxicity Through Modulation of CYP2E1 Gene Expression in Hepatic Cells of Wistar Rats

The present study was aimed to assess the hepatoprotective effect of ethanolic extract of Garcinia gummi-gutta (GGE) fruit rind on acetaminophen-induced toxicity in a rat model and to explore the possible mechanism of action by assessing hepatic histopathology, serum bio­chemical parameters and expression of CYP2E1 gene in hepatic cells. The group I and 11 animals served as normal control and hepatotoxic control group, respectively; while group III, IV and V were administrated with GGE fruit-rind extract @ 50, 100 & 200 mg kg-1 orally, respectively, for 10 days. The group VI (positive control) received drug silymarin @ 100 mg kg-1 day-1 orally for 10 days. Hepatotoxicity was induced by single oral administration of acetaminophen (2 g kg-1) on 8th day. The results revealed that the extract produced dose-dependent hepatoprotective effect against acetaminophen-induced hepatic damage by improving the serum bio­chemical profile towards the normal range. Histopathology of liver showed that pretreatment with fruit-rind extract attenuated the toxicant-induced hepatocellular necrosis and enhanced the regeneration of hepatic cells. The hepatic expression level of CYP2E1 gene was found down-regulated in a dose dependent manner in extract-treated group as compared to the normal control group. The study revealed remarkable hepatoprotective effect of GGE in acetaminophen-induced toxicity in rats through regeneration of hepatic cells and by decreasing the formation of reactive metabolite, NAPQ1 by modulation of CYP2E1 gene expression in liver.

Justicia secunda Vahl leaf fraction protects against acetaminophen-induced liver damage in rats by alleviating oxidative stress and enhancing membrane-bound phosphatase activities

Objective: To investigate the effect of Justicia secunda Vahl leaf fraction against acetaminophen-induced oxidative damage in the liver of rats. Methods: In vitro antioxidant assays were performed on Justicia secunda leaf fractions. Gas chromatography-mass spectrometry analytical method was done. Experimental animals were orally administered with 2 g/kg b.wt. acetaminophen, 100-500 mg/kg b.wt. Justicia secunda ethyl acetate leaf fraction (JSELF), and 100 mg/kg b.wt. silymarin. Blood and liver were collected to measure hepatic, oxidative stress, and membrane-bound phosphatase markers. Results: JSELF had significantly (P Conclusions: JSELF could protect against oxidative stress and improve membrane-bound phosphatase activity in rats with acetaminophen-induced hepatic damage.

Structural characterization, antioxidant and hepatoprotective activities of polysaccharides from Sophorae tonkinensis Radix

In current study we present two polysaccharides, STRP1 and STRP2, purified from Sophorae tonkinensis Radix via column chromatography. Structural analyses indicated that STRP1 and STRP2 were consisted of mannose, rhamnose, glucuronic acid, glucose, galactose and arabinose in a similar molar ratio with main backbones of (1 → 3)-linked-α-d-Gal and (1 → 4)-linked-α-d-Glc, while average molecular weights were 1.30 × 104 and 1.98 × 105 Da, respectively. We observed a strong chelating ability on ferrous ions; substantial radical scavenging activities on DPPH, hydroxyl and superoxide anion radicals in vitro; and significant attenuation on acetaminophen-induced hepatic oxidative damage in mice for STRP1 and STRP2. The promising data on these polysaccharides showcase the need to further develop novel natural antioxidant and liver-protecting drugs.

Hepatoprotective potential of Phyllanthus muellarianus leaf extract: studies on hepatic, oxidative stress and inflammatory biomarkers

Context: Leaves of Phyllanthus muellarianus (Kuntze) Exell. (Euphorbiacea) are widely used in the management of liver disorders in Nigeria. However, no there is no scientific validation to support this use. Objective: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was investigated in acetaminophen-induced liver injury mice. Materials and methods: Hepatoprotective effect of Phyllanthus muellarianus aqueous leaf extract was evaluated in acetaminophen-induced hepatic damage in Swiss albino mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Mice received distilled water, 100, 200, or 400 mg/kg b.w of Phyllanthus muellarianus aqueous leaf extract, respectively, for seven days. Treatment groups were challenged with 300 mg/kg b.w of acetaminophen on the sixth day. Results: Oral administration of Phyllanthus muellarianus aqueous leaf extract significantly (p < 0.05) attenuates acetaminophen-mediated alterations in serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin and total bilirubin by 76.56, 85.41, 89.39, 82.77 and 78.38%. Similarly, acetaminophen-mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase were significantly attenuated in the liver of mice by 85.10, 80.81, 80.45, 76.23 and 95.22%, respectively. Increased levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl, fragmented DNA, tumor necrosis factor-α, interleukin-6 and -8 were significantly lowered by Phyllanthus muellarianus aqueous leaf extract. Conclusion: Overall, results of this study show that Phyllanthus muellarianus halted acetaminophen-mediated hepatotoxicity due to its capability to enhance antioxidant enzymes.

Lophirones B and C Attenuate Acetaminophen-Induced Liver Damage in Mice: Studies on Hepatic, Oxidative Stress and Inflammatory Biomarkers

Lophirones B and C are chalcone dimers with proven chemopreventive activity. This study evaluates the hepatoprotective effect lophirones B and C in acetaminophen-induced hepatic damage in mice using biomarkers of hepatocellular indices, oxidative stress, proinflammatory factors and lipid peroxidation. Oral administrations of lophirones B and C significantly (p < 0.05) attenuated acetaminophen-mediated alterations in serum alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin and total bilirubin. Similarly, acetaminophen-mediated decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose 6- phosphate dehydrogenase were significantly attenuated in the liver of mice. Increased levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl and fragmented DNA were significantly lowered by lophirones B and C. Levels of tumour necrosis factor-α, interleukin-6 and 8 were significantly lowered in serum of acetaminophen treated mice by the chalcone dimers. Overall, results of this study show that lophirones B and C halted acetaminophen-mediated hepatotoxicity.

HEPATOPROTECTIVE AND ANTIOXIDANT EFFECTS OF AZOLLA MICROPHYLLA BASED GOLD NANOPARTICLES AGAINST ACETAMINOPHEN INDUCED TOXICITY IN A FRESH WATER COMMON CARP FISH (CYPRINUS CARPIO L.)

Objective(s): Our present study sought to evaluate hepatoprotective and antioxidant effects of methanol extract of Azolla microphylla phytochemically synthesized gold nanoparticles (GNaP) in acetaminophen (APAP) - induced hepatotoxicity of fresh water common carp fish. Materials and Methods: GNaP were prepared by green synthesis method using methanol extract of Azolla microphylla. Twenty four fishes weighing 146 ± 2.5 g were used in this experiment and these were divided into four experimental groups, each comprising 6 fishes. Group 1 served as control. Group 2 fishes were exposed to APAP (500 mg/kg) for 24 h. Groups 3 and 4 fishes were exposed to APAP (500 mg/kg) + GNaP (2.5 mg/kg) and GNaP (2.5 mg/kg) for 24 h, respectively. The hepatoprotective and antioxidant potentials were assessed by measuring liver damage, biochemical parameters, ions status, and histological alterations. Results: APAP exposed fish showed significant elevated levels of metabolic enzymes (LDH, G6PDH and MDH), hepatotoxic markers (GPT, GOT and ALP), reduced hepatic glycogen, lipids, protein, albumin, globulin, increased levels of bilirubin, creatinine, and oxidative stress markers (TBRAS, LHP and protein carbonyl), altered the tissue enzymes (SOD, CAT, GSH-Px and GST) non-enzyme (GSH), cellular sulfhydryl (T-SH, P-SH and NP-SH) levels, reduced hepatic ions (Ca 2+ , Na + and K + ), and abnormal liver histology. It was observe that GNaP has reversal effects on the levels of above mentioned parameters in APAP hepatotoxicity. Conclusion: Azolla microphylla phytochemically synthesized GNaP protects liver against oxidative damage and tissue damaging enzyme activities and could be used as an effective protector against acetaminophen-induced hepatic damage in fresh water common carp fish.

Preventive Effect of the Korean Traditional Health Drink (Taemyeongcheong) on Acetaminophen-Induced Hepatic Damage in ICR Mice.

This study was to investigate the preventive effect of taemyeongcheong (TMC, a Korean traditional health drink) on acetaminophen (APAP, 800 mg/kg BW)-induced hepatic damage in ICR mice. TMC is prepared from Saururus chinensis, Taraxacum officinale, Zingiber officinale, Cirsium setidens, Salicornia herbacea, and Glycyrrhizae. A high dose of TMC (500 mg/kg BW) was found to decrease APAP-induced increases in serum levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase. TMC pretreatment also increased the hepatic levels of hepatic catalase, superoxide dismutase, glutathione peroxidase, and glutathione, and reduced serum levels of the inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 in mice administered APAP (P<0.05). TMC (500 mg/kg BW) reduced hepatic mRNA levels of TNF-α, IL-1β, IL-6, COX-2, and iNOS by 87%, 84%, 89%, 85%, and 88%, respectively, in mice treated with APAP (P<0.05). Furthermore, histological observations suggested TMC pretreatment dose-dependently prevented APAP-induced hepatocyte damage. These results suggest that TMC could be used as a functional health drink to prevent hepatic damage.

Hepatoprotective and antioxidant activity of Karisalai Karpam, a polyherbal Siddha formulation against acetaminophen-induced hepatic damage in rats.

Background:The usage of Siddha medicine in Tamil Nadu and several parts of Southern India has considerably increased over the past two decades and it is steadily crossing the various geographies owing to its inexpensiveness compared to conventional medicines and has fairly high acceptance rates because of its herbal origin and therefore its nontoxic nature.Aim:This study aims to investigate the anti-hepatotoxic and antioxidant potential of the Karisalai Karpam formulation.Materials and Methods:Karisalai Karpam tablet at 50, 100, and 200 mg/kg/day, p.o. doses were administered orally to rats for three consecutive days. Single dose of acetaminophen (3 g/kg, p.o.) was administered on the 3rd day. Animals were sacrificed 48 h after the administration of acetaminophen, and their serum bilirubin, different hepatic enzymes and in vivo antioxidant activity were estimated.Statistical Analysis:Data were evaluated using analysis of variance, followed by Tukey tests. A level of P < 0.05 was considered statistically significant.Results:Pretreatment with Karisalai Karpam tablet showed dose-dependent hepatoprotective activity. Karisalai Karpam tablet (200 mg/kg) reduces serum glutamic oxaloacetate transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase and total bilirubin, direct bilirubin by 67.8%, 72.3%, 47.6%, 61.3% and 62.9% respectively compared to disease control group. A significant increase (P < 0.001) in antioxidant enzyme level was observed in Karisalai Karpam treated animals. At higher doses, Karisalai Karpam prevented the depletion of glutathione in liver tissue.Conclusion:Results confirmed that Karisalai Karpam tablet could protect the liver against acetaminophen-induced oxidative damage possibly by increasing the antioxidant defence mechanism in rats.

Hepatoprotective Effect of Pretreatment with Rosemary and Ginger Essential Oil in Experimental Model of Acetaminophen-induced Injury

Aims: Liver diseases have become one of the major causes of morbidity and mortality all over the world. This study investigated the hepatoprotective and antioxidant effect of rosemary essential oil (REO) and ginger essential oil (GEO), against paracetamol-induced liver damage. Methodology: The hepatoprotective effects of REO and GEO at doses of 125, 250 and 500 mg/kg, respectively, orally for 7 days were determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity. In vitro antioxidant activity of REO and GEO were evaluated by assessing the free radical 2, 2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging activity and lipid peroxidation. Results: REO and GEO reduced the levels of the serum marker enzymes AST, ALT, and MPO activity. The essentials oils also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. Conclusion: These results suggest that REO and GEO have hepatoprotective effects on acetaminophen-induced hepatic damage in mice probably due to their antioxidant effect.

Essential oils: new perspectives in human health and wellness.

Essential oils: new perspectives in human health and wellness.

Hepatoprotective Effect of Pretreatment with Thymus vulgaris Essential Oil in Experimental Model of Acetaminophen‐Induced Injury

Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO), which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging effects of TEO and TEO-induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen-induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen-induced hepatic damage in mice.

Protective Effect ofAcacia nilotica(L.) against Acetaminophen-Induced Hepatocellular Damage in Wistar Rats

The potential biological functions of A. nilotica have long been described in traditional system of medicine. However, the protective effect of A. nilotica on acetaminophen-induced hepatotoxicity is still unknown. The present study attempted to investigate the protective effect of A. nilotica against acetaminophen-induced hepatic damage in Wistar rats. The biochemical liver functional tests Alanine transaminase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin, total protein, oxidative stress test (Lipid peroxidation), antioxidant parameter glutathione (GSH), and histopathological changes were examined. Our results show that the pretreatment with A. nilotica (250 mg/kg·bw) orally revealed attenuation of serum activities of ALT, AST, ALP, liver weight, and total bilirubin levels that were enhanced by administration of acetaminophen. Further, pretreatment with extract elevated the total protein and GSH level and decreased the level of LPO. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by acetaminophen. The present study undoubtedly provides a proof that hepatoprotective action of A. nilotica extract may rely on its effect on reducing the oxidative stress in acetaminophen-induced hepatic damage in rat model.

The Influence Of Annona Muricata Leaves Extract In Damaging Kidney Cell And Inducing Caspase-9 Activity

Annona muricata leaf extract is used in Indonesia traditional medicine for the treatment of many disease . Work done has demonstrated Annona muricata to be effective in treating carbon tetrachloride-and acetaminophen-induced hepatic damage, In this present study, the efficacy of ethanolic extracts of Annona muricata leaves for its cytotoxicity potential and induction of apoptosis in tubular cells, was investigated. Phytochemical screening verified presence of alkaloids, tannins, flavonoids, saponins, anthraquinones and cardiac glycosides. The present study was undertaken to investigate the leaf extract effects of Annona muricata Linn. on the level of serum creatinine and damage of tubular cell structure that effect of kidney cell functions and caspase-9 expression in glomerulus and tubular cells. The animals (n=20) Were grouped a (control), I, II, AND III (experimental). The experimental animals of group I were administered with 10 mg/kg body weight/ day annona muricata extract in saline for 40 days, group II were administered with 20 mg/kg body weight/ day annona muricata extract in saline for 40 days and III were administered with 40 mg/kg body weight/day annona muricata extract in saline for 40 days and then we see the effect on creatinine serum concentration by ELISA method and glomerulus,tubular cells were fixed and processed to examine the histological changes and caspase-9 expression in glomerulus and tubular cells.

Liver Protective Activity of the Methanol Extract of Crinum jagus Bulb against Acetaminophen-induced Hepatic Damage in Wistar Rats

Liver Protective Activity of the Methanol Extract of Crinum jagus Bulb against Acetaminophen-induced Hepatic Damage in Wistar Rats

Bilirubin Lowering Potential of &lt;i&gt;Annona muricata&lt;/i&gt; (Linn.) In Temporary Jaundiced Rats

Problem statement: Annona muricata is used in Ghanaian traditional medicine for the treatment of jaundice. Work done has demonstrated A. muricata to be effective in treating carbon tetrachloride-and acetaminophen-induced hepatic damage, hepatic jaundice and toxicologically safe up to 1000 mg kg -1 in animals. Current study evaluated the bilirubin- lowering potential of A. muricata aqueous extract in phenylhydrazine-(40 mg kg -1 ) induced jaundice in adult rats. Approach: Jaundice was assessed by measuring the levels of total bilirubin and direct bilirubin in phenylhydrazine-treated an imals with or without drug treatment with curative, proph ylactic study and in animals with reduced liver capacity. Results: Phenylhydrazine induced jaundice in animals from 1.50 �mol L -1 ±0.00 total bilirubin in normal animals up to 29.25 �mol L -1 ±2.21 in animals with reduced liver capacity. The hyperbilirubinaemia were restored close to normal l evels in animals treated with A. muricata aqueous extract at 50 and 400 mg kg -1 . Total bilirubin level was reduced to 6.22 �mol L -1 ± 0.27 at 50 mg, 5.68 �mol L -1 ±0.36 at 400 mg kg -1 and 7.94 �mol L -1 ±0.79 with Silymarin, significantly lower (p<0.001) compared with the vehicle group (16.90 �mol L -1 ±2.21) maintained with distilled water. Conclusion: Therefore, A. muricata aqueous extract can be used to reduce bilirubin co ncentration in jaundiced subjects.

17β-Estradiol protects against acetaminophen-overdose-induced acute oxidative hepatic damage and increases the survival rate in mice

Acetaminophen overdose causes acute liver injury or even death in both humans and experimental animals. We investigated the effect of 17β-estradiol against acetaminophen-induced acute liver injury and mortality in mice. Male mice were given acetaminophen (p-acetamidophenol; 300 mg/kg; orally) to induce acute liver injury. Acetaminophen significantly increased the levels of aspartate transaminase, alanine transaminase, myeloperoxidase, lipid peroxidation, and glutathione reductase, but it decreased superoxide dismutase, catalase, and glutathione. In addition, acetaminophen-induced mortality began 4 h post-treatment, and all mice died within 9 h. 17β-Estradiol (200 μg/kg; i.p.) protected against acetaminophen-induced oxidative hepatic damage by inhibiting neutrophil infiltration and stimulating the antioxidant defense system. However, 17β-estradiol did not affect acetaminophen-induced glutathione depletion or increased glutathione reductase activity. We conclude that 17β-estradiol specifically attenuates acute hepatic damage and decreases mortality in acetaminophen-overdosed male mice.

Protective Effects of Syringic Acid against Acetaminophen-Induced Hepatic Damage in Albino Rats

The protective effect of the phenolic compound syringic acid, one of the major benzoic acid derivatives from edible plants and fruits, was evaluated against acetaminophen (APAP)-induced hepatotoxicity in rats. Toxicity was induced in adult male albino Wistar rats by the administration of APAP (750 mg/kg body weight) intraperitoneally. Rats were treated with syringic acid (25, 50, and 100 mg/kg body weight) by the oral route. We assessed the activity of hepatic markers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Lipid peroxidative markers thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and a decrease in enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and non-enzymatic antioxidants vitamin C, vitamin E and reduced glutathione levels. Liver histology also showed convincing evidence regarding their protective nature against fatty changes induced during APAP intoxication. Syringic acid administered at a dose of 50 mg/kg body weight significantly decreased the activities of hepatic and renal function markers to near normal values when compared with the other two doses. The results suggest that syringic acid could afford a significant protective effect against APAP induced hepatic damage in rats.

Hepatoprotective Effect of Amukkarac curanam in Acetaminophen Intoxicated Rats

Objective: The hepatoprotective action of Amukkarac curanam (AC), a widely used Siddha medicine was evaluated using acetaminophen-induced hepatic damage in rats. Material and methods: AC was administered orally at a dose of 500 mg/kg body weight for 7 days. Serum levels of transaminase (AST, ALT), alkaline phosphate (ALP), bilirubin, Total protein (TP) and albumin (Alb) were used as the biochemical markers of hepatotoxicity. Liver thiobarbituric acid reactive substances and histopathological studies were also done to confirm the biochemical changes. Results and Discussion: The results of the study indicate that pretreatment with AC significantly reversed the increased levels of serum marker enzymes such as AST, ALT, ALP and bilirubin, when compared to acetaminophen-induced group. The level of liver thiobarbituric acid reactive substances was also brought to near normal. AC has protected the liver from acetaminophen-induced damage. Probable mechanism of action is by protection against oxidative damage produced by acetaminophen.

The potential protective role of alpha-lipoic acid against acetaminophen-induced hepatic and renal damage

The potential protective role of alpha-lipoic acid (α-LA) in acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity was investigated in rats. Pretreatment of rats with α-LA (100 mg/kg) orally protected markedly against hepatotoxicity and nephrotoxicity induced by an acute oral toxic dose of APAP (2.5 g/kg) as assessed by biochemical measurements and by histopathological examination. None of α-LA pretreated animals died by the acute toxic dose of APAP. Concomitantly, APAP-induced profound elevation of nitric oxide (NO) production and oxidative stress, as evidenced by increasing of lipid peroxidation level, reducing of glutathione peroxidase (GSH-Px) activity and depleting of intracellular reduced glutathione (GSH) level in liver and kidney, were suppressed by pretreatment with α-LA. Similarly, daily treatment of rats with a smaller dose of α-LA (25 mg/kg) concurrently with a smaller toxic dose of APAP (750 mg/kg) for 1 week protected against APAP-induced hepatotoxicity and nephrotoxicity. This treatment also completely prevented APAP-induced mortality and markedly inhibited APAP-induced NO overproduction and oxidative stress in hepatic and renal tissues. These results provide evidence that inhibition of NO overproduction and maintenance of intracellular antioxidant status may play a pivotal role in the protective effects of α-LA against APAP-induced hepatic and renal damage.