Paracetamol-induced Liver Damage Research Articles

Hepatocellular Changes on Paracetamol Induced Liver Damage in Long Evans Male Rats upon Green Tea Administration

Background: The liver is a vital organ that serves a number of purposes in our body. It may be harmed by pollutants, substances with toxic effects, and long-term, unchecked drug use. Green tea is a well-liked beverage that has gained popularity recently and may have hepatoprotective properties. Objective: To observe the effect of green tea (Camellia sinensis) on paracetamol induced liver damage in Long Evans male rats. Methods: From July 1st, 2018, to June 30th, 2019, this study was conducted in the Department of Physiology at Sir Salimullah Medical College (SSMC), Dhaka. For the purpose of the study, thirty (30) male Long Evans rats, weighing between 150 and 200 grams and 90 to 120 days old, appeared to be in good health. They were split into two groups after 14 days of acclimatization: Group A, which served as the control group, and Group B, which served as the experimental group (green tea pretreatment and paracetamol treated). Group A1 (baseline control group) and group A2 (paracetamol treated control group) comprised the subdivided control group. There were ten rats in each of these groups. For 28 days, the rats were all fed a baseline diet. The baseline control group was given normal saline (20 ml/kg/day) orally every day for 28 days in addition to their basal diet. For the final three days of the study—the 26th and 28th—the paracetamol-treated control group was given oral paracetamol at a dose of 1.5 g/kg/day. During the final three days of the study period (the 26th and 28th days), the experimental group was given oral paracetamol (1.5g/kg/day) and an ethanolic extract of green tea (500 mg/kg/day) for a total of 28 days. On day 29, every rat was sacrificed. Following the sacrifice, liver samples were taken. Hepatic contents of malondialdehyde (MDA) were measured by using standard laboratory method. Histopathology of liver was also done by using standard laboratory procedure in the department of pathology, SSMC. Version 22 of the Statistical Package of Social Science (SPSS) for Windows was used to do the statistical analysis. The data were displayed as mean±SD. To compare the results, one-way ANOVA, post hoc Bonferroni, and Chi-square tests were used, where appropriate. A p value of less than 0.05 was regarded as significant. Result: When compared to the baseline control group, the mean malondialdehyde concentration in the liver was significantly (p) greater in the green tea pretreatment, paracetamol treated, and control groups who received paracetamol treatment. Once more, the groups treated with green tea and paracetamol had mean malondialdehyde concentrations in their livers that were significantly (p) lower than those of the paracetamol group. Additionally, 0% of the rats in the baseline control group, 100% of the rats in the paracetamol-treated group, and 30% of the rats in the green tea-pretreated and paracetamol-treated group had abnormal histological findings of the liver. Conclusion: This study revealed that green tea has hepatoprotective effect against paracetamol induced liver damage in Long Evans male rats. Bangladesh Crit Care J September 2024; 12 (2): 145-152

Hepatoprotective Activity of Patra Swarasa of Guduchi (Tinospora Cordifolia) Against- Paracetamol Induced

Guduchi (Tinospora cordifolia (Willd.) Miers], Menispermaceae family, it is important medicinal plant is widely distributed through India. It is categorized as "Rasayana" and the whole plant is used medicinally. The aim of the present study is to evaluate the protective effect of Guduchi patra swaras against paracetamol induced liver damage in Wister albino rats. Material & Methods: Wistar Albino rats (140-250g) will be divided into 6 group and each group 6 rats, into control group, paracetamol control, standard group, test group. The test drug Guduchi patra swarasa was administered orally for 10 consecutive days and two dose of the toxicant (paracetamol) were administered orally to each group, on two alternate days i.e., 7th and 9th day, 1hr after test drug administration. After 48 hours of toxicant paracetamol, and standard group. The blood was collected in EDTA tube and sent for biochemistry laboratory for biochemical investigations. Result: The analysis of serum biochemical parameters shows that administration of paracetamol leads to significant change in majority of the parameters. The overall activity profile indicated reversal of important parameters like SGOT, SGPT, total bilirubin, total protein, blood sugar level, serum globulin, serum albumin, serum total cholesterol and serum triglycerides. All three test groups of Guduchi patra Swarasa administered are found to be effective heapto-protective especially based on histo-pathological study. Among the three groups, the double dose group and therapeutic group has shown good results in comparison with the other two groups. Conclusion: In the present study, the overall activity profile of Guduchi patra Swarasa administered are found to be effective hepatoprotective among the three groups therapeutic double dose shows good results in comparison with the other group.

Mitigating of Paracetamol-induced Hepatotoxicity in Albino Mice Using Boerhaavia diffusa Extracts

Boerhaavia diffusa, renowned for its therapeutic efficacy in chronic liver diseases, operates through multifaceted mechanisms to uphold internal homeostasis. Its pivotal roles encompass modulation of intermediary metabolism of macromolecules, synthesis of crucial plasma proteins, enzymatic activities, and bile excretion.In this investigation, we aimed to evaluate the hepatoprotective potential of Boerhaavia diffusa against paracetamol-induced hepatotoxicity in rats. Our study revealed promising outcomes as the extracts obtained from Boerhaavia diffusa demonstrated a significant hepatoprotective role in albino rats subjected to hepatotoxicity induced by paracetamol administration. During the study, the animals were administered doses of 1g/kg b.wt and 2 g/kg b.wt of the plant extracts. Following paracetamol administration, conspicuous changes were observed in hepatocyte biochemical markers, indicative of hepatotoxicity. However, treatment with Boerhaavia diffusa extracts ameliorated these alterations, underscoring their potential to mitigate paracetamol-induced liver injury. These findings underscore the significant hepatoprotective properties inherent in the plant extracts derived from Boerhaavia diffusa. which can be utilized as a potential therapeutic avenue for the management of paracetamol-induced liver damage. These findings hold promise for the development of novel therapeutic interventions aimed at safeguarding liver health and mitigating the adverse effects of hepatotoxic insults.

Investigating the hepatoprotective properties of thymol against paracetamol-induced hepatotoxicity

The current research investigates thymol, a compound known for its antioxidant, antimicrobial, antifungal, antidiabetic, and analgesic properties, to assess its potential to protect the liver and determine how it might mitigate liver damage induced by paracetamol. For this study, the experimental animals were divided into five different groups, including a vehicle control group, a negative control group with paracetamol-induced liver damage, a positive control group treated with silymarin, and two groups treated with thymol in addition to paracetamol exposure. Liver function tests, histopathological analysis, and assessment of the activities of antioxidant enzymes were performed to assess the hepatoprotective effects of thymol treatment. Results revealed that treatment with thymol significantly restored the liver function markers to their normal values, including serum enzyme levels and lipid profiles, in paracetamol-induced liver damage. The histopathological examination demonstrated enhanced structural integrity of hepatocytes, decreased instances of necrotic cell death, and reduced infiltrated inflammatory cells in the groups treated with thymol. Furthermore, thymol treatment effectively increased superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) quantities in liver tissues. Overall, these results suggest that thymol has significant protective effects against paracetamol-induced liver toxicity through multiple mechanisms, including restoration of liver function, attenuation of oxidative stress, and preservation of hepatocyte integrity.

A Comparison of the Protective Effect of Pyridoxine and N-Acetylcysteine in Paracetamol Induced Hepatotoxicity in Rats

Paracetamol is a common over the counter drug. Paracetamol-induced hepatotoxicity results in over 300,000 hospitalizations each year and accounts for up to 42% of all cases of acute liver failure. N-acetylcysteine (NAC) is a potential antidote to manage paracetamol toxicity. Objective: To investigate the effects of pyridoxine, alone and in combination with NAC in repairing paracetamol-induced liver damage in male Wister rats. Methods: A single oral dose of paracetamol (650 mg/kg) was administered to Wistar rats to induce hepatotoxicity. The hepato-protective effects of NAC at a dose 300 mg/kg, and pyridoxine (200 mg/kg) were evaluated using standard liver function tests and histopathological along with serum glutathione levels. Results: The administration of pyridoxine and NAC resulted in a significant decrease in AST, ALT, and total bilirubin levels and the reversal of histopathological changes. Conversely, administering NAC and pyridoxine in combination yielded significant changes except for the glutathione level. Conclusions: The study concluded that pyridoxine may be used as a potential hepatoprotective drug in paracetamol-induced hepatotoxicity. In combination with NAC, it showed protective effects in paracetamol-induced hepatoxicity.

Histopathological and Immunohistochemical Evaluation of the Protective Effect of the Flavonoid Fustin in a Rat Model of Paracetamol-induced Acute Liver Damage

Histopathological and Immunohistochemical Evaluation of the Protective Effect of the Flavonoid Fustin in a Rat Model of Paracetamol-induced Acute Liver Damage

Investigation of catalytic properties of glutathione reductase obtained by chromatographic methods from the liver of rats with paracetamol-induced liver damage upon administration of 6-hydroxy-2,2,2,4-trimethyl-1,2-dihydroquinoline

The aim of the present study was to analyze some catalytic and regulatory properties of the enzyme preparation of glutathione reductase (GR, EC 1.6.4.2.) obtained from rat liver using gel filtration and ion exchange chromatography under conditions of paracetamol-induced liver injury (PILI) and administration of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (DHQ). Laboratory animals (Rattus norvegicus rats of the Wistar line) were divided into 3 groups. The animals of the control group were orally administered vaseline oil. The second group consisted of rats with PILI induced by a single oral administration of paracetamol at a dose of 1000 mg/kg body weight dissolved in 1 cm3 of vaseline oil. Animals of the third group were modeled by PILI and orally administered with DHQ at a dose of 50 mg per 1 kg body weight dissolved in 1 cm3 of 1% starch, 1 hour and 12 hours after paracetamol administration. Liver and serum were collected 24 hours after paracetamol administration. GR activity was measured on a spectrophotometer at 340 nm wavelength. The enzyme was purified from rat liver by ammonium sulfate fractionation, gel filtration through Sephadex G-25, and ion exchange chromatography on DEAE-cellulose. The total amount of protein in the samples was measured using the BCA protein assay kit. GR was obtained from the liver of rats treated with DHQ on the background of PILI with a 32-fold purification degree. Using the method of double inverse Lineweaver-Burk coordinates it was shown that administration of DHQ to rats was accompanied by a decrease in the affinity of the enzyme for NADPH, as compared to the indicators at pathology. The introduction of isocitrate into the spectrophotometric medium resulted in a less pronounced increase in the activity of GR from the liver of animals treated with DHQ on the background of PILI, compared to the second group of rats. The enzyme from the liver of animals of the third group was characterized by a more significant decrease in activity when glucose-6-phosphate was introduced into the reaction medium. Citrate had a less pronounced regulatory effect on GR from the liver of rats treated with DHQ on the background of pathology, relative to the indicators of animals with PILI. The changes in enzyme properties demonstrated may be due to conformational changes in the molecule resulting from the inhibition effect of DHQ on the intensity of free radical-induced oxidation, which develops against the background of the toxic effect of paracetamol metabolites.

Hepatoprotective effect of the flavonoid fustin in a rat model of paracetamol-induced acute liver damage

Paracetamol (PCM)-induced toxicity is a well-established pharmacological model. Cotinus coggygria is a medicinal plant rich in polyphenols, including the flavonoid fustin. The aim of the present study was to evaluate the effects of the flavonoid fustin isolated from Cotinus coggygria heartwood in a model of PCM-induced liver damage. Male Wistar rats (n=48) were allocated to four groups: Control, PCM, F5+PCM, F10+PCM. The rodents were treated daily orally for nine consecutive days as follows: groups F5+PCM and F10+PCM – with fustin (suspended in a vehicle) at doses of 5 and 10 mg/kg, respectively; groups Control and PCM – with the vehicle. PCM was injected intraperitoneally (1.0 g/kg) on day 7. At the end of the experiment, serum and liver samples were prepared. PCM caused a severe liver damage confirmed by histopathological, immunohistochemical and biochemical indices. Compared to PCM group, in F5+PCM and F10+PCM groups, the hepatic necrosis, steatosis, ballooning degeneration, inflammation and expression of NF-κB were significantly reduced. Fustin treatment resulted in a significant reduction of serum activities of alanine aminotransferase and gamma-glutamyl transferase to levels that did not differ from the control values. The present study demonstrated a hepatoprotective effect of the flavonoid fustin in a rat model of acute paracetamol-induced toxicity.

Ethanolic Extract of Citrus Sinensis Peel Markedly Mitigate Paracetamol-Induced Hepatotoxicity in Rats

Background: Herbal medicines have historically been crucial for enhancing human health. Previous studies have highlighted the antioxidant properties of various parts of Citrus sinensis. In light of widespread reliance on plant-based remedies, this study focuses on a particular herbal medicine, Citrus sinensis, known for its rich content of vitamin C, pectins, phenolic compounds, and flavonoids. Objective: This research aims to investigate the hepatoprotective potential of the ethanolic extract of Citrus sinensis peel in vivo, particularly focusing on its antioxidant capabilities. Methods: The study utilized biochemical parameters including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and total proteins to assess the hepatoprotective action of the Citrus sinensis peel extract in serum of Wistar albino rats. The rats were divided into five groups, with varying treatments including a control group, a paracetamol-induced hepatotoxicity group, and groups receiving different doses of the Citrus sinensis extract. Results: Treatment with the ethanolic extract of Citrus sinensis peel at doses of 200 mg/kg and 400 mg/kg significantly mitigated the paracetamol-induced elevation of serum levels of AST, ALT, ALP, bilirubin, and total proteins. These improvements were comparable to those observed with the standard drug, silymarin. Conclusion: The study confirms the hepatoprotective effects of Citrus sinensis peel extract against paracetamol-induced liver damage. This protection was evident both biochemically and histopathologically, suggesting the potential therapeutic utility of Citrus sinensis in liver disorders.

Assessment of the hepatoprotective effect of Moringa oleifera leaves ex-tract (MOLE) on paracetamol-induced hepatotoxicity in Albino Wistar rats

The current study aimed to investigate the hepatoprotective efficacy of Moringa oleifera (MOLE) against liver damage in male rats caused by paracetamol. Four groups of twenty-four male Wister rats, weighing between 150 and 200 gm each, were created. To cause liver damage, a dose of 2g/kg of paracetamol was given once a day for a week, and a dose of 300mg/kg B.W. of MOLE was given orally via gavage for four weeks. As an example hepatoprotective medication, silymarin was administered orally at a rate of 100 mg/kg body weight. Enzyme levels in the liver including total bilirubin, ALT, AST, and ALP were utilized to gauge the extent of recovery after hepatic damage. As antioxidant enzymes, SOD and CAT were evaluated. In male rats, paracetamol-induced liver damage was successfully avoided by silymarin and MOLE. The hepatoprotective effects of the extract were evidenced by a noteworthy reduction in the levels of blood enzymes include TB, ALT, AST, and ALP, along with a decline in tumour necrosis factor alpha (TNF-α). Additionally, there was a rise in the levels of antioxidant enzymes SOD and CAT, as well as interleukin 6 (IL-6).

Impact of α-Tocopherol and Ascorbic Acid Pre-Treatment on Paracetamol Induced Liver Injury in Wistar Albino Male Rats

Background: Liver injury may occur by toxic dose of paracetamol administration where liver function markers are elevated and centrilobular hepatic necrosis is visible under a microscopic observation in hepatic lobule configuration. α-tocopherol and ascorbic acid are known antioxidant and they may have hepatoprotective effect against paracetamol induced liver damage. Aim of the study: The aim of this study was to evaluate the effects of α-tocopherol and ascorbic acid on paracetamol induced liver damage in Wistar albino male Rats. Methods: This was an animal model experimental study which was conducted in the Department of Physiology, Sir Salimullah Medical College, Dhaka, Bangladesh from 1st January to 31st December, 2017. Although primarily healthy Wister albino male rats, 90-120 days old, weighing from 160 to 200g were selected for this study, finally data were analyzed on 30 rats. Finalized 30 samples were divided into three groups Group I (baseline control group, n=10), Group II (paracetamol treated control group, n=10) and Group III (combined α-tocopherol with ascorbic acid pretreated & paracetamol treated group n=10). The dose of α-tocopherol 100 mg/kg Body weight and ascorbic acid 200 mg/kg Body weight per day orally were selected as pre-exposure prophylaxis. The statistical analyses were done by one-way ANOVA and Bonferroni test, paired ‘t’ test and Fisher’s Exact test as applicable. Results: The mean serum total bilirubin, ALT and AST were significantly increased in group II and III in comparison to that of group I except the serum levels of total bilirubin and ALT of group III which were increased than that of group I but it was not statistically significant. Again, the mean MDA concentration in liver was significantly increased in group II in comparison to that of group I whereas though this level was increased in group III than that of group I but it was statistically not significant. Furthermore, the mean serum levels of total bilirubin, ALT, AST and ...

Boric acid is associated with the suppression of apoptosis and endoplasmic reticulum stress in rat model of paracetamol -induced hepatotoxicity

Paracetamol (also known as acetaminophen or APAP) is an analgesic and antipyretic drug that is widely used all over the world. Boron is an element proven by many studies that it has indispensable effects on human health. In light of the information expressed about boron, we investigated whether there are any effects of boron on paracetamol-induced liver damage. We analyzed the 8-hydroxyguanosine (8-OHG), ALT, AST, glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and nitric oxide (NO) levels in serum or erythrocyte and liver tissue. At the same time, TNF-α, IL-1β, IL-18 levels were examined in liver tissues to determine the effect of boron on inflammation caused by paracetamol in serum and liver tissue. In this study to determine the effect of ER stress-mediated apoptosis, signal transducers that lead the cell to ER stress-mediated apoptosis, IRE1, ATF6 and PERK, caspase 1, 3, 8, 9 and 12, which play a role in the apoptotic process, antiapoptotic factors bcl2, bcl-xL mRNA gene expressions were determined and the effect level of boron on ER stress-mediated apoptosis was determined by immunohistochemical methods. This study demonstrate that boric acid protects against paracetamol-induced liver damage in association with the augmentation of biomarkers of oxidative and nitrosative stress, inflammation and the ER stress / apoptosis axis in rats.

UHPLC-QTOF-MS Metabolic Profiling of Marchantia polymorpha and Evaluation of Its Hepatoprotective Activity Using Paracetamol-Induced Liver Injury in Mice.

Marchantia species were traditionally used to treat liver failure. Marchantia polymorpha chloroform extract showed a marked hepatoprotective activity in a dose-dependent manner in paracetamol-induced extensive liver damage in mice. At a dose of 500 mg/kg (MP-500), it resulted in a reduction in aspartate transaminase by 49.44%, alanine transaminase by 44.11%, and alkaline phosphatase by 24.4% with significant elevation in total proteins by 58.69% with respect to the diseased group. It showed significant reductions in total bilirubin, total cholesterol, triglycerides, low density lipoprotein (LDL), very LDL, total lipids, and to high density lipoprotein ratio (CH/HDL) by 53.42, 30.14, 35.02, 45.79, 34.74, 41.45, and 49.52%, respectively, together with a 37.69% increase in HDL with respect to the diseased group. It also showed an elevation of superoxide dismutase by 28.09% and in glutathione peroxidase by 81.83% in addition to the reduction of lipid peroxidation by 17.95% as compared to the paracetamol only treated group. This was further supported by histopathological examination that showed normal liver architecture and a normal sinusoidal gap. Metabolic profiling by ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF/MS) led to the tentative identification of 28 compounds belonging to phenols, quinolones, phenylpropanoid, acylaminosugars, terpenoids, lipids, and fatty acids to which the activity was attributed. Four compounds were detected in the negative ionization mode which are neoacrimarine J, marchantin A, chitobiose, and phellodensin F, while the rest were detected in the positive mode. Thus, it can be concluded that this plant could serve as a valuable choice for the treatment of hepatotoxicity that further consolidated its traditional use.

Hepatoprotective Effect of Herbal Medicinal Plant Extract against Paracetamol Induced Liver Injury in Rats

The purpose of this study was to examine the hepatoprotective efficacy of Whole plant extract of Adiantum capillus against Paracetamol induced liver damage in rats. Wistar albino rats were orally fed 500 mg/kg of body weight of Methanolic and Acetonic extract of Adiantum capillus Whole plant, with Silymarin serving as the reference. By restoring functional parameters, physical parameters, biochemical parameters, and decreasing blood enzymes alkaline phosphatase (ALP) and total bilirubin (TBL) in the selected animal, the methanolic and Acetonic extracts exhibited a potent hepatoprotective effect. The plant's chemical composition includes, among others, alkaloids, flavonoids, glycosides, steroids, terpenoids, phenolics, and saponins. The overall experimental data suggest that bioactive phytoconstituents, such as flavonoids and alkaloids, present in the Methanolic and Acetonic extracts of Adiantum capillus plant may be responsible for the plant's significant hepatoprotective effect. The results thus support the use of Adiantum capillus plant as a hepatoprotectant.

Hepatoprotective activity of lycopene in experimental paracetamol-induced liver injury in rats

Aim: To evaluate the hepatoprotective effects of lycopene pretreatment in paracetamol-induced liver damage (PILD). Methods: Wistar rats were administered oral lycopene (4 mg/kg/day) by gastric lavage for 8 days. Subsequently, 3 g/kg paracetamol was administered on day 8. After 24 and 72 h, animals were euthanized, and intracardiac blood samples were collected to measure levels of aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transferase, and alkaline phosphatase (ALP). In addition, the liver was harvested for histological analyses. Results: Negative and positive control groups (treated with saline or paracetamol on day 8, respectively) were compared with lycopene- and lycopene-paracetamol-treated (lycopene+paracetamol on day 8) groups. Notably, we observed that 24 h after PILD, lycopene treatment significantly reduced serum transaminase (ALT/AST) levels when compared with those in the saline-treated group. Conclusion: Lycopene improved liver recovery following PILD. Although lycopene exhibits antioxidant action and has been indicated for liver diseases, its use must be cautiously undertaken, especially considering the liver patholog y involved, as results may vary for each underlying factor.

Comparative Effects of α-Tocopherol and Ascorbic Acid Pre-Treatment on Paracetamol-Induced Liver Damage in Wistar Albino Rats

Comparative Effects of α-Tocopherol and Ascorbic Acid Pre-Treatment on Paracetamol-Induced Liver Damage in Wistar Albino Rats

Effects of <i>Sarcocephalus latifolius</i> Fruits Extract on Paracetamol-Induced Liver Damage in Wistar Rats

Background and Aim: Sarcocephalus latifolius is a medicinal plant commonly used in traditional medicine to treat various diseases. The aim of the present study is to evaluate the hepatoprotective activity of Sarcocephalus latifolius fruits aqueous extract against paracetamol-induced liver damage in rats. Material and Methods: Aqueous extract of Sarcocephalus latifolius fruits at doses of 100, 250 and 500 mg/kg were administered orally to rats with paracetamol-induced hepatotoxicity (1 g/kg). The treatment with the extract and paracetamol lasted 7 days. Silymarin (50 mg/kg) was given as reference control. All tested drugs were administered orally. Results: Our results show that the Sarcocephalus latifolius fruits extract induced a significant reduction (p Conclusion: Aqueous extract of Sarcocephalus latifolius fruits has hepatoprotective activity against paracetamol-induced hepatotoxicity in rats. But it would be important to evaluate the activity of aqueous extract of Sarcocephalus latifolius fruits on oxidative stress parameters in vivo in rats.

The Prophylactic Anti-Inflammatory Effect of Omega-7 Against Paracetamol-Induced Liver Injury in Rats


 
 
 
 Paracetamol poisoning, whether intentionally or accidentally, is one of the main public health problems since the prevalence of its toxicity increased significantly in many countries. Currently, paracetamol is one of the primary causes of acute liver failure worldwide. The aim of this study was to investigate the potential prophylactic effect of omega-7 fatty acid in protecting male rats' livers from paracetamol-induced liver damage. Thirty albino male rats were divided randomly and equally into five groups and then treated as follows: Group 1 (negative control) rats were orally given liquid paraffin for seven consecutive days. Group 2 (positive control) rats were orally given liquid paraffin for seven consecutive days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. Group 3 rats were orally given omega-7 (300 mg/kg) for seven consecutive days. Group 4 rats were orally given a single dose of omega-7 (100 mg/kg/day) for 7 days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. Group 5 rats were orally given a single dose of omega-7 (300 mg/kg/day) for 7 days and a single injection of paracetamol (500 mg/kg) intraperitoneally on day eight of the experiment. After 24 h of the endpoint of treatment (on day 9), blood samples were collected, and serum was prepared for the evaluation of tumor necrosis factor-alpha (TNF-α) and interleukin-10 (IL-10). This study found that rats given paracetamol had a significant (P<0.05) increase in serum levels of TNF-α and IL-10, whereas rats previously given oral administration of omega-7 fatty acid before injection of paracetamol resulted in a significant decrease (P<0.05) of these cytokines. Oral omega-7 fatty acid supplementation may help to prevent liver damage caused by paracetamol.
 
 
 

Evaluation of Hepatoprotective Activity of Aqueous Extract of Nyctanthes Arbortristis Bark against Paracetamol-Induced Liver Damage

Herbal drugs aimed to determine the hepatoprotective activity of aqueous extract of Nyctanthes arbortristis bark (AQENA) against paracetamol-induced liver damage (PILD) in rat models. Four groups of rats (n=6) were givens one daily administration of 1gm/kg (negative control), 25mg/kg silymarin (positive control) and AQENA (500mg/kg) for 7 days fallowed by induction of hepatotoxicity using of paracetamol. Various parameters, such as physical parameters, biochemical parameters and microscopic analysis ware used to evaluate the hepatoprotective activity. Results indicate that bark extract would a significant (p<0.05) hepatoprotective activity against inducers. These observations were supported by the histological finding. Conclusions: Findings indicate that AQENA possesses a potent hepatoprotective activity against paracetamol.

GC–MS analysis, and evaluation of protective effect of Piper chaba stem bark against paracetamol-induced liver damage in Sprague-Dawley rats: Possible defensive mechanism by targeting CYP2E1 enzyme through in silico study

The present study attempted to scrutinize the protective effect of the methanolic extract of P. chaba stem bark against paracetamol-induced hepatotoxicity in Sprague−Dawley rats, along with the gas chromatography–mass spectrometry (GC–MS) analysis to identify phytochemicals, which were further docked in the catalytic site of CYP2E1 and the MD simulation for system that plays a major role in the bio-activation of toxic substances that produce reactive metabolites, leading to hepatotoxicity. P. chaba stem methanol extract (250 and 500 mg/kg) were treated orally with the negative control and the negative control silymarin (50 mg/kg) groups. Phytochemical profiling was conducted using GC–MS. In in-silico studies, PyRx software was used for docking analysis and the stability of the binding mode in the target active sites was evaluated through a set of standard MD-simulation protocols using the Charmm 27 force field and Swiss PARAM. Co-administration of P. chaba at both doses with APAP significantly reduced the APAP-augmented liver marker enzymes ALT, AST, ALP, and LDH, along with serum albumin, globulin, hepatic enzymes, histopathological architecture, lipid profiles, total protein, and total bilirubin, and elevated the levels of MDA. The GC–MS analysis indicated that P. chaba extract is enriched in fatty acid methyl esters (46.23 %) and alkaloids (10.91 %) and piperine is represented as a main phytochemical. Among all the identified phytochemicals, piperine (−8.0 kcal/mol) was found to be more interacting and stable with the binding site of CYP2E1. Therefore, all of our findings may conclude that the P. chaba stem extract and its main compound, piperine, are able to neutralize APAP-induced hepatic damage.