Paracetamol-induced Liver Injury Research Articles

Paracetamol-induced Liver Injury in An Experimental Rat Model: Noninvasive Assessment using DKI and the Effect of Gadoxetate on DKI Parameters.

To explore the potential of diffusion kurtosis imaging (DKI) for assessing the degree of liver injury in a paracetamol-induced rat model and to simultaneously investigate the effect of intravenous gadoxetate on DKI parameters. Paracetamol was used to induce hepatoxicity in 39 rats. The rats were pathologically classified into 3 groups: normal (n=11), mild necrosis (n=18), and moderate necrosis (n=10). DKI was performed before and, 15 min, 25 min, and 45 min after gadoxetate administration. Repeated-measures ANOVA with Tukey's multiple comparison test was used to investigate the effect of gadoxetate on mean diffusivity (MD) and mean diffusion kurtosis (MK) and to assess the differences in MD and MK among the three groups. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic accuracy of the MD values when discriminating between the necrotic groups. Gadoxetate had no significant effect on either the MD or the MK, and the effect size was small. The MD in the moderate necrosis group was significantly lower than that in the other two groups (F = 13.502, p < 0.001; η2 = 0.428 [95% CI: 0.082-0.637]), while the MK did not significantly differ among the three groups (F = 2.702, p = 0.081; η2 = 0.131 [95% CI: 0.001-0.4003]). The AUCs of MD for discriminating the moderate necrosis or normal group from the other groups were 0.921 (95% CI: 0.832-1.000) and 0.831 (95% CI: 0.701-0.961), respectively. It would be better to measure the MD and MK before gadoxetate injection. MD showed potential for assessing the degree of liver necrosis in a paracetamol-induced liver injury rat model.

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.

Cardioprotective and Hepatoprotective Potential of Silymarin in Paracetamol-Induced Oxidative Stress.

Silymarin, derived from Silybum marianum, has been used in traditional medicine for various ailments. In this study, the cardioprotective and hepatoprotective effects of silymarin against paracetamol-induced oxidative stress were examined in 28 male Swiss Webster mice, divided into four groups and treated for 7 days (via the oral route) with (a) saline 1 mL/kg (control group), (b) saline 1 mL/kg + single dose of paracetamol 110 mg/kg on the 7th day; (c) silymarin 50 mg/kg; and (d) silymarin 50 mg/kg + single dose of paracetamol 110 mg/kg on the 7th day. In vitro and in vivo antioxidant activity together with liver enzyme activity were evaluated. Histopathological and immunohistochemical assessment was performed. Silymarin mitigated paracetamol-induced liver injury by reducing oxidative stress markers such as lipid peroxidation and restoring antioxidant enzyme activity. Silymarin treatment resulted in a significant decrease in liver enzyme levels. Reduced necrosis and inflammatory infiltrate in liver tissues of silymarin-treated groups were detected as well. Immunohistochemical analysis demonstrated reduced expression of inflammatory markers (COX2, iNOS) and oxidative stress marker (SOD2) in the liver tissues of the silymarin-treated groups. Similar trends were observed in cardiac tissue. These results suggest that silymarin exerts potent hepatoprotective and cardioprotective effects against paracetamol-induced oxidative stress, making it a promising therapeutic agent for liver and heart diseases associated with oxidative 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.

Hippocratea africana Root Extract and Fractions Ameliorates Paracetamol (PCM)-Induced Oxidative Stress and Liver Injuries in Rats

Aim: The antidotal potential of Hippocratea africana root, which is used locally to cure poisoning, was studied in rats.&#x0D; Methodology: The hepatoprotective activity of the root extract (200-600 mg/kg), fractions (dichloromethane (DCM) and aqueous, 400 mg/kg) and Silymarin (100 mg/kg), were investigated against paracetamol-induced liver injury in rats. Assay of liver function parameters, markers of antioxidative stress in addition to liver histological analysis were employed to evaluate the hepatoprotective potential of root extract and fractions.&#x0D; Results: Administration of the root extract (200-600 mg/kg) caused significant (P &lt; .05-.001) increases in the blood levels of total protein and decreases in direct and total bilirubin, and the liver biomarker enzymes ALT, AST, and ALP caused by paracetamol administration. Most of the time, the effects were dose-dependent. When compared to the negative control group of animals (organotoxic-treated animals), the histology of the liver sections from animals treated with extract, fractions, and silymarin revealed a decrease in pathological characteristics. These histological observations suggest significant hepatoprotective potentials which were in line with the chemical pathological alterations.&#x0D; Conclusion: The outcome of the study indicated that root extract and fractions of Hippocratea africana have antioxidative stress potentials and hepatoprotective action against harmful substances, maybe as a result of its phytochemical constituents' activity.

Effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury

Objective: Evaluate the effectiveness of resveratrol as a hepatoprotector in a rat model of paracetamol-induced liver injury and its biodistribution to understand its pharmacokinetics. Methodology: As an experimental approach, animals were divided into the test group with 4 subgroups and the control group with 4 subgroups. Animals of the "treated" group were subjected to resveratrol pre-treatment for eight days, followed by intoxication with a high dose of paracetamol on the 8th day. Animals were euthanized to collect the blood and liver tissue samples 24 and 72 h after the last administration. Hepatoprotective activity was evaluated through serum levels of glycogen and hepatic enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), histological and morphometric analysis of the liver tissue. For biodistribution analysis, different organs (organs, kidneys, heart and lungs) were collected and macerated, and resveratrol was quantified using high-performance liquid chromatography. Statistical analyses of morphometry, transaminases and alkaline phosphatase measurements, and biodistribution results were performed using GraphPad Prism® 3.0. Differences between groups were compared using ANOVA, followed by the Bonferroni test. Statistical significance was set at p &lt; 0.05.

Đánh giá tác dụng chống oxy hóa và bảo vệ gan trên thực nghiệm của cây muồng lùn

Antioxidant and hepatoprotective effects of different fractions of extract from Chamaecrista pumila (Lam.) K. Larsen were investigated by employing in vitro and in vivo models, respectively. In vitro antioxidant activity of ethanol extract and its n-hexan, ethyl acetate, chloroform, n-butanol and remained water fraction extracts obtained from C. pumila was assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide radical scavenging assay. In vitro results revealed that the ethanol extract had potential DPPH radical and superoxide radical scavenging activities with an IC50 value of 18.65 (9.91-35.08) µg/ml and 12.33 (5.24-29.02) µg/mL, respectively. Among fractions extracted from ethanol extract, the ethyl acetate fraction possessed highest antioxidant property through DPPH radical scarvenging activity with an IC50value of 9.98 (6.23-16.01) µg/mL and superoxide radical scavenging activity with an IC50 value of 8.38 (6.11-11.50) µg/mL. In vivo hepatoprotective activities of ethanolic extract and ethyl acetate fraction obtained from C. pumila were investigated in mice using a model of paracetamol-induced hepatotoxicity. Ethanol extract of C. pumila at doses of 250 mg/kg and 500 mg/kg decreased levels of serum transaminases ASAT. Ethyl acetate fraction of C. pumila at doses of 250 mg/kg and 500 mg/kg significantly improved the parameters of paracetamol-induced liver injury including ASAT, ALAT and superoxide dismutase (SOD) activities; ethyl acetat fraction of C. pumila at dose of 500 mg/kg also exhibited in vivo antioxidant properties by reducing malondialdehyde (MDA) content and increasing glutathione (GSH) content.

The Effect of Curcumin Nanoparticles on Paracetamol-Induced Liver Injury in Male Wistar Rats.

Curcumin is a naturally occurring compound that has antioxidant properties, acts as a hepatoprotective, and lowers lipid peroxidation. However, curcumin's low solubility and bioavailability are its primary drawbacks and prevent its use as a therapeutic agent. In this study, curcumin nanoparticles will be created using the ultrasonic-assisted extraction method, and their effectiveness against paracetamol-induced changes in ALT, AST, SOD, MDA, and TNF-α will be compared to that of pure curcumin. This study aimed to determine the hepatoprotective effect of curcumin nanoparticles in paracetamol-induced rats as a model for liver injury. Thirty-six male Wistar rats, aged 6 to 8 weeks, with a minimum weight of 120 grams, were used in an experimental laboratory investigation with a post-test-only group design. Rats in each group received 100 mg/kgBW pure curcumin, 100 mg/kgBW curcumin nanoparticles, and 50 mg/kgBW curcumin nanoparticles for 7 days before paracetamol induction. On day 8, 300 mg/kgBW of paracetamol was intraperitoneally injected to cause liver damage. One of the groups received NAC as an antidote 10 hours after paracetamol induction. Detection of ALT and AST using a Chemistry Analyzer. ELISA approach for the detection of SOD, MDA, and TNF-α. The Roenigk score was calculated by two examiners after the liver histopathology preparations were stained using the Hematoxylin-Eosin method. Post hoc analyses were performed after the One Way Annova and Kruskal Wallis tests to examine the data. According to PSA results, the smallest formula that formed curcumin nanoparticles (10.2 nm) was 8 g of curcumin formula mixed with a mixture of Tween 20 4.5 ml, Kolliphor EL 1.5 ml, Propylene Glycol 1.5 ml, and Capryol 90 1 ml for 21 minutes using an ultrasonic process. MDA and TNF-α levels, as well as the liver's histological Roenigk score, were significantly lower in the 100 mg/kgBB pure curcumin group (C100) when compared to the model group (model). The levels of AST, MDA, TNF-α, and the liver histopathology score were significantly lower in the 100 mg/kgBB (NC100) and 50 mg/kgBB (NC50) curcumin nanoparticle groups compared to the model group (model) and pure curcumin group (C100) (p< 0.05). Curcumin nanoparticles showed better hepatoprotective ability than pure curcumin.

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 &amp; 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 ...

Interleukin-35 and Thymoquinone nanoparticle-based intervention for liver protection against paracetamol-induced liver injury in rats

Paracetamol (PAR) is a commonly used antipyretic and analgesic agent, but its excessive usage can induce liver damage and major health consequences. Interleukin-35 (IL-35) is utilized to treat immunological disorders, intestinal illness, arthritis, allergic disease, hepatitis, and cancer. Thymoquinone (THYO) is also effective against a wide range of disorders. Consequently, this study sought out to explore the ameliorative effects of IL-35 and THYO against PAR-induced hepatotoxicity in rats. Sixty male rats were separated into six groups (10 rats/group): I control (0.5 mL NaCl, 0.9%/rat via oral gavage); II (IL-35), and III (TYHO) received intraperitoneal (i.p) injection of IL-35 (200 ng/kg) or THYO (0.5 mg/kg), respectively. Group IV (PAR) received 600 mg/kg of PAR orally; V (PAR + IL-35) and VI (PAR + TYHO); rats received 600 mg/kg of PAR orally and i.p injection of IL-35 (200 ng/kg) or THYO (0.5 mg/kg), respectively. Administration of IL-35 or THYO markedly mitigated the increasing in the levels of liver parameters triggered by PAR and noticeable enhancement of antioxidant and immunological markers were observed. Additionally, IL-35 or THYO decreased TNF-α, NF-κB, IL-10, IL-6 and IFN-γ in contrast to the PAR control group. Moreover, levels of Capase-3, and cytochrome C were significantly reduced by THYO or IL35, while, levels of Bcl-2 were markedly increased. Furthermore, significant downregulation of IL1-β, TNF-α, TGF-β, and Caspas-3 genes, as well as significant upregulation of Bcl-2 and IL-10 expression were detected. In conclusion, IL-35 and THYO insulated liver from PAR toxicity by mitigating oxidative stress, tissue damage, inflammation, and apoptosis.

Liver protective effect of chloroform extract of Bauhinia purpurea leaves is attributed partly to its antioxidant action and the presence of flavonoids

Context Bauhinia purpurea L. (Fabaceae) is used in the Ayurvedic system to treat various oxidative-related ailments (e.g., wounds, ulcers etc.). Therefore, it is believed that the plant also has the potential to alleviate oxidative-related liver damage. Objective This study elucidates the hepatoprotective activity of chloroform extract of B. purpurea leaves (CEBP) in paracetamol (PCM)-induced liver injury (PILI) rats. Materials and methods Male Sprague-Dawley rats (n = 6) were pre-treated once daily (p.o.) with CEBP (50–500 mg/kg) for seven consecutive days before being administered (p.o.) a hepatotoxic agent, 3 g/kg PCM. Liver enzyme levels were determined from the collected blood, while the collected liver was used to determine the activity of endogenous antioxidant enzymes and for histopathological examination. CEBP was also subjected to radical scavenging assays and phytochemical analysis. Results CEBP significantly (p < 0.05) reversed the toxic effect of PCM by increasing the serum levels of AST and ALT, and the activity of endogenous catalase (CAT) and superoxide dismutase (SOD) while reducing the liver weight/body weight (LW/BW) ratio. Other than low TPC value and radical scavenging activity, CEBP had a high antioxidant capacity when evaluated using the oxygen radical absorbance capacity (ORAC) assay. UHPLC-ESI-MS analysis of CEBP showed the presence of flavonoids. Discussion and conclusions CEBP exerts its hepatoprotective activity through a non-free radical scavenging pathway that involves activation of the endogenous enzymatic antioxidant defense system. Further study is needed to identify the responsible bioactive compounds before the plant can be developed as a future alternative hepatoprotective medicament for clinical use.

Pharmacokinetics and safety of prolonged paracetamol treatment in neonates: An interventional cohort study.

To investigate the pharmacokinetics and safety of prolonged paracetamol use (>72 h) for neonatal pain. Neonates were included if they received paracetamol orally or intravenously for pain treatment. A total of 126 samples were collected. Alanine aminotransferase and bilirubin were measured as surrogate liver safety markers. Paracetamol and metabolites were measured in plasma. Pharmacokinetic parameters for the parent compound were estimated with a nonlinear mixed-effects model. Forty-eight neonates were enrolled (38 received paracetamol for >72 h). Median gestational age was 38 weeks (range 25-42), and bodyweight at inclusion was 2954 g (range 713-4750). Neonates received 16 doses (range 4-55) over 4.1days (range 1-13.8). The median (range) dose was 10.1mg/kg (2.9-20.3). The median oxidative metabolite concentration was 14.6μmol/L (range 0.12-113.5) and measurable >30 h after dose. There was no significant difference (P > .05) between alanine aminotransferase and bilirubin measures at <72 h or >72 h of paracetamol treatment or the start and end of the study. Volume of distribution and paracetamol clearance for a 2.81-kg neonate were 2.99 L (% residual standard error = 8, 95% confidence interval 2.44-3.55) and 0.497 L/h (% residual standard error = 7, 95% confidence interval 0.425-0.570), respectively. Median steady-state concentration from the parent model was 50.3μmol/L (range 30.6-92.5), and the half-life was 3.55 h (range 2.41-5.65). Our study did not provide evidence of paracetamol-induced liver injury nor changes in metabolism in prolonged paracetamol administration in neonates.

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.

Sumc (Rhus coriaria L.) fruit ameliorates paracetamol-induced hepatotoxicity

Sumac [Rhus coriaria L. (Anacardiaceae)] is a widely used spice in the Middle East. In this study, the hepatoprotective effects of sumac fruit were evaluated using a rat model of paracetamol-induced liver injury. The experimental design relies on the pretreatment of rats with intraperitoneal sumac extract followed by a toxic dose of paracetamol. Tissue alterations, serum levels of oxidative stress markers, as well as gene expression of immunomarkers were evaluated. Rats pre-treated with sumac displayed attenuated signs of toxicity. Upon paracetamol intoxication, sumac-pretreated animals showed a minimal increase in liver enzyme levels. In parallel, serum albumin and total protein levels were close to normal. Moreover, pretreated sumac animals had preserved hepatocyte morphology, whereas unprotected animals had necrotic deformations. Importantly, these effects were dose-dependent and comparable to the silymarin-treated positive control group. In conclusion, sumac extract offers a potential hepatoprotective regimen against xenobiotic-induced hepatotoxicity and for oxidative stress management.

Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats.

Toxic doses of paracetamol are also known to be close to therapeutic doses. This study aimed to biochemically investigate the protective effect of ATP against paracetamol-induced oxidative liver injury in rats and to examine the tissues histopathologically. We divided the animals into the paracetamol alone (PCT), ATP + paracetamol (PATP), and healthy control (HG) groups. Liver tissues were examined biochemically and histopathologically. Malondialdehyde level, AST and ALT activity in the PCT group were significantly higher than those in the HG and PATP groups (p < 0.001). The glutathione (tGSH) level, superoxide dismutase (SOD) and catalase (CAT) activity in the PCT group was significantly lower than that in the HG and PATP groups (p < 0.001), while animal SOD activity was significantly different between the PATP and HG groups (p < 0.001). The activity of CAT was almost the same. In the group treated with paracetamol alone, lipid deposition, necrosis, fibrosis, and grade 3 hydropic degeneration were observed. No histopathological damage was observed of the ATP-treated group, except for grade 2 edema. We discovered that ATP reduces the oxidative stress caused by paracetamol ingestion and protects against paracetamol-induced liver injury at the macroscopic and histological levels.

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

&#x0D; &#x0D; &#x0D; &#x0D; 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&lt;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&lt;0.05) of these cytokines. Oral omega-7 fatty acid supplementation may help to prevent liver damage caused by paracetamol.&#x0D; &#x0D; &#x0D; &#x0D;

Preliminary phytochemical and hepatoprotective studies of ethanol extract of Desmodium repandum (Vahl) D.C. in paracetamol induced liver injury in guinea pig

Medicinal plants are used worldwide in folk medicine to treat many diseases, including those affecting the liver, but most of those plants are not yet studied. The present study aimed at the in vivo evaluation of the hepatoprotective potential and doing a preliminary phytochemical screening of Desmodium repandum (Vahl) D.C. leaves ethanolic extract, a plant used in many regions of Africa to treat liver diseases. The presence of main phytochemical groups was assessed by using specific reactions of identification. Hepatoprotective activity was evaluated in male guinea pigs; the hepatotoxicity was induced by oral administration of paracetamol (acetaminophen) at the dose of 500 mg/kg. Silymarin was used as the reference drug at the dose of 100 mg/kg, the control group received a solution of carboxymethylcellulose (CMC) 1%, and the experimental groups 100 and 200 mg of the extract per kg of body weight. The results of phytochemical screening revealed the presence of anthocyanin, phenolic compounds, coumarins, flavonoids, quinones, tannins, sterols, and triterpenes. At the dose of 200 mg/kg, the extract reduced significantly (p ˂ 0.05) the blood concentration of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin after intoxication by paracetamol comparatively to the control group. This work demonstrated for the first time the hepatoprotective potential of the ethanolic extract of Desmodium repandum (Vahl) D.C. leaves.

Preliminary phytochemical and hepatoprotective studies of ethanol extract of Desmodium repandum (Vahl) D.C. in paracetamol induced liver injury in guinea pig

Preliminary phytochemical and hepatoprotective studies of ethanol extract of Desmodium repandum (Vahl) D.C. in paracetamol induced liver injury in guinea pig