Paracetamol-induced Liver Toxicity Research Articles

Phytochemical Contents, GC-MS Analysis and Hepatoprotective Effect of the Methanol Leaf Extract of Camelliasinensis (L.) Kuntze on Paracetamol-Induced Liver Injury in Wistar Rats

BACKGROUND AND OBJECTIVES: _Camellia sinensis_ is a tree popularly called green tea used as a strong antioxidant and for treating diseases such as cancer. This present study was aimed at assessing the phytochemicals and evaluating the hepatoprotective activity of leaf extract in Wistar rats. METHODS: The phytochemical screening was performed by standard methods, GC-MS analysis was carried out in Agilent 7890 A GC coupled to a MS detector, acute toxicity study was evaluated by the OECD guidelines, and hepatoprotective activity were evaluated in randomly groups of five rats of six rats in paracetamol-induced liver toxicity, while liver biomarkers were evaluated using automated methods. RESULTS: The phytochemical screening of leaf extract revealed the presence of major metabolites. The GC-MS analysis showed 18 bioactive compounds which are mainly fatty acids with retention times between 7.436 and 18.462 min. A high total phenolic content (TPC) of 1425.22 mg GAE/g and a total flavonoid content (TFC) of 802.01 mg QE/g were obtained. The acute toxicity did not produce any sign of toxicity at a dose of 5,000 mg/kg of extract. The extract produced a dose-dependent activity on the liver. These protections were statistically significant (p<0.05) when compared to the standard drug silymarin. There were no elevated values in liver function biomarkers in all the animal groups as well as histopathological damages to the liver after eight weeks of treatment at 200 and 400 mg/kg b.w. of extract doses. CONCLUSION: In conclusion, the study showed that _C. sinensis_ methanol leaf extract contains important phytochemicals that are protective against paracetamol-induced liver injuries, thus, the plant was considered safe for use as ethnomedicinal remedies for liver disease in traditional medicine.

Evaluation of capillary miR-122 as a prognostic biomarker of paracetamol-induced liver toxicity.

Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose. In a paracetamol overdose patient cohort, miR-122 was measured by quantitative polymerase chain reaction in a blood drop obtained by a finger prick at the end of an antidote cycle treatment with N-acetylcysteine treatment (12h). Liver injury was defined as serum alanine aminotransferase (ALT) activity > 100IU/L collected at 10 or 20h after the start of treatment. Pearson's correlation analyses were performed. In patients with paracetamol overdose, capillary miR-122 was positively correlated with ALT measured at 10h and at 20h (r = 0.83, P < 0.0001; r = 0.96, P < 0.0001, respectively). This work supports the potential use of capillary miR-122 as a prognostic biomarker of liver injury throughout clinical management of patients with paracetamol overdose. Capillary miR-122 can be measured in a blood drop collected by a finger prick, a minimally invasive diagnostic test for patient stratification.

The use of Phytochemical, GC-MS Analysis and Hepatoprotective Effect of the Methanol Leaf Extract of Camellia Sinensis (L.) Kuntze on Paracetamol-Induced Liver Injury in Wistar Rats

BACKGROUND AND OBJECTIVES: Camellia sinensis is a tree popularly called green tea used as a strong antioxidant and for treating diseases such as cancer. This present study was aimed at assessing the phytochemicals and evaluating the hepatoprotective activity of leaf extract in Wistar rats. METHODS: The phytochemical screening was performed by standard methods, acute toxicity study and hepatoprotective activity were evaluated in randomly groups of five rats or six rats in paracetamol-induced liver toxicity. RESULTS: The phytochemical screening of leaf extract revealed the presence of major metabolites. The GC-MS analysis showed 18 bioactive compounds which are mainly fatty acids with retention times between 7.436 and 18.462 min. A high total phenolic content (TPC) of 1425.22 mg GAE/g and a total flavonoid content (TFC) of 802.01 mg QE/g were obtained. The acute toxicity did not produce any sign of toxicity at a dose of 5,000 mg/kg of extract. The extract produced a dose-dependent activity on the liver. These protections were statistically significant (p&lt;0.05) when compared to the standard drug silymarin. There were no elevated values in liver function biomarkers in all the animal groups as well as histopathological damages to the liver after eight weeks of treatment at 200 and 400 mg/kg b.w. of extract doses. CONCLUSION: In conclusion, the study showed that C. sinensis methanol leaf extract contains important phytochemicals that are protective against paracetamol-induced liver injuries, thus, the plant was considered safe for use as ethnomedicinal remedies for liver disease in traditional medicine.

Protective effects of jervine purified from Veratrum album on paracetamol-induced liver toxicity in rats

Purpose: Since paracetamol toxicity is a very common type of poisoning, we planned to investigate whether Jervine has an effect on paracetamol toxicity by utilizing its anti-inflammatory effect.&#x0D; Materials and Methods: In our study, 42 Sprague Dawley rats of 8 weeks of age were used. Seven groups were formed with 6 animals in each group. At the 24th hour of the study, all groups underwent laparotomy under anesthesia, and liver dissection was performed. Hematoxylin and Eosin (H&amp;E) staining was performed to evaluate liver histopathology. SOD, CAT, GSH, and MDA levels were analyzed biochemically.&#x0D; Results: Histopathological, while liver tissues were normal in the control group, we observed degeneration areas, inflammation, and hemorrhage in the paracetamol group. Jervine reduced the severity of paracetamol toxicity and prevented liver damage. Jervine significantly increased SOD levels. Paracetamol administration significantly decreased CAT levels. Paracetamol significantly decreased GSH levels compared to the control group. &#x0D; Conclusion: Jervine reduced the adverse effects of paracetamol toxicity on liver tissue, such as degeneration, inflammation, and hemorrhage. Jervine increased antioxidant activity and reduced the harmful effects of NAPQI, the toxic metabolite of paracetamol, on liver tissue.

Taming Food-Drug Interaction Risk: Potential Inhibitory Effects of Citrus Juices on Cytochrome Liver Enzymes Can Safeguard the Liver from Overdose Paracetamol-Induced Hepatotoxicity.

Paracetamol overdose is the leading cause of drug-induced hepatotoxicity worldwide. Because of N-acetyl cysteine's limited therapeutic efficacy and safety, searching for alternative therapeutic substitutes is necessary. This study investigated four citrus juices: Citrus sinensis L. Osbeck var. Pineapple (pineapple sweet orange), Citrus reticulata Blanco × Citrus sinensis L. Osbeck (Murcott mandarin), Citrus paradisi Macfadyen var. Ruby Red (red grapefruit), and Fortunella margarita Swingle (oval kumquat) to improve the herbal therapy against paracetamol-induced liver toxicity. UHPLC-QTOF-MS/MS profiling of the investigated samples resulted in the identification of about 40 metabolites belonging to different phytochemical classes. Phenolic compounds were the most abundant, with the total content ranked from 609.18 to 1093.26 μg gallic acid equivalent (GAE)/mL juice. The multivariate data analysis revealed that phloretin 3',5'-di-C-glucoside, narirutin, naringin, hesperidin, 2-O-rhamnosyl-swertisin, fortunellin (acacetin-7-O-neohesperidoside), sinensetin, nobiletin, and tangeretin represented the crucial discriminatory metabolites that segregated the analyzed samples. Nevertheless, the antioxidant activity of the samples was 1135.91-2913.92 μM Trolox eq/mL juice, 718.95-3749.47 μM Trolox eq/mL juice, and 2304.74-4390.32 μM Trolox eq/mL juice, as revealed from 2,2'-azino-bis-3-ethylbenzthiazoline-6-sulfonic acid, ferric-reducing antioxidant power, and oxygen radical absorbance capacity, respectively. The in vivo paracetamol-induced hepatotoxicity model in rats was established and assessed by measuring the levels of hepatic enzymes and antioxidant biomarkers. Interestingly, the concomitant administration of citrus juices with a toxic dose of paracetamol effectively recovered the liver injury, as confirmed by normal sections of hepatocytes. This action could be due to the interactions between the major identified metabolites (hesperidin, hesperetin, phloretin 3',5'-di-C-glucoside, fortunellin, poncirin, nobiletin, apigenin-6,8-digalactoside, 6',7'-dihydroxybergamottin, naringenin, and naringin) and cytochrome P450 isoforms (CYP3A4, CYP2E1, and CYP1A2), as revealed from the molecular docking study. The most promising compounds in the three docking processes were hesperidin, fortunellin, poncirin, and naringin. Finally, a desirable food-drug interaction was achieved in our research to overcome paracetamol overdose-induced hepatotoxicity.

Hepatoprotective activity of Balsamodendron mukul extract against Paracetamol-induced liver toxicity in rats: In vivo pharmacological and toxicological evaluation

Overuse of the antipyretic agent Paracetamol (PCM) is linked to hepatotoxicity, which limits its clinical use. The goal of this investigation was to find out how well Balsamodendron mukul (B.mukul) extract protects the liver from acute PCM poisoning. B.mukul extract was procured from a standard crude drug supplier in the local market. The PCM-induced hepatotoxicity was screened in experimental animals. Animals that were treated only with excessive PCM (2g/kg) had changes in their serum biomarkers (i.e., serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, and serum total bilirubin), oxidative stress, Tumor Necrosis Factor-α (TNF-α), and Interleukin-1 proteins. B.mukul extracts of 245μg and 332μg revealed 50% of hydroxyl radical scavenging and lipid peroxidation inhibiting, respectively, which was found to be more significant when compared to ascorbic acid treatment. The outcomes confirmed that B.mukul extract has strong antioxidant activity, which leads to the inhibition of reactive oxygen species (ROS). Treatment with B.mukul extract at doses of 300 and 600mg/kg produced a dose-dependent reduction in the PCM-induced rise of the biochemical parameters. Silymarin at 100mg/kg body weight significantly prevented such rise in the study. Finally, the findings confirmed that the B.mukul extract has more potent than silymarin and revealed higher antioxidant and hepatoprotective activity, which could consider a novel approach for the reduction of PCM-induced liver toxicity.

Investigation of hepatoprotective effect of aqueous extract of calliste-mon viminalis (AECV) in paracetamol-induced liver toxicity in male rats

The current study was performed to investigate the hepatoprotective potential of Callistemon viminalis (AECV) on paracetamol –induced liver damage in male rats. Twenty-four male Wister rats (150–200 gm) were divided into 4 groups (6 animals each). Paracetamol was given at a dose of 2g/kg once daily for one week to induce liver injury, while AECV was administered via oral gavage at a dose of 200mg/kg B.W. for 4 weeks. Silymarin was given orally as reference hepatoprotective drug at a dose of 100mg/kg B.W. Liver enzymes such as ALT, AST, ALP, and total bilirubin were used to determine the level of hepatic injury recovery. SOD and CAT were measured as antioxidant enzymes. Both AECV and silymarin were successful in preventing the liver damage caused by paracetamol in male rats. The extract's hepatoprotective properties were demonstrated by a significant decrease in the blood enzymes ALT, AST, ALP, and TB and an increase in the antioxidant enzymes SOD and CAT.

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.

Hepato-Protective Effect of Telfaria occidentalis (Ugwu) Leaves Supplementation in Paracetamol Induced-Toxicity in Rats

The hepato-protective effect of Telfaria occidentalis leaves supplementation on paracetamol induced liver toxicity in wistar rats was investigated. A total of forty Wistar (female and male) rats weighing between 150-250g were selected for the study. The animals were randomly divided into four groups of five animals each. Animals in group 1 and 2 received standard chow only while animals in group 3 and 4 received 5% and 10% T. occidentalis supplementation in their feed respectively for six weeks. Group 2, 3 and 4 were administered 3000 mg/kg bodyweight of paracetamol intraperitoneally after six weeks. The animals were sacrificed after 24hours of induction and the liver was harvested for analysis. Alanine transaminase, Aspartate Transaminase and Alkaline Phosphatase, total protein, total bilirubin and direct bilirubin were measured in the liver homogenate following standard methods. A significant decrease in the level of ALT, AST and ALP, Bilirubin and increased total protein in group 3 and 4 were observed when compared with group 2. This study showed that T. occidentalis leaves possess protective potential on the liver when supplemented in the diet thereby preventing deleterious effects that might arose from paracetamol overdose or overuse. The study concluded that the protective effect of the leaves on the liver is percentage supplementation (dose) dependent.

Morin: a promising nutraceutical therapy for modulation of the NF-kB/NOX-2/IL-6/HO-1 signaling pathways in paracetamol-induced liver toxicity

Introduction: Paracetamol overdose potentially causes liver injury. This study aimed to evaluate the impact of morin against paracetamol overdose-induced hepatotoxicity. Methods: Thirty albino rats weighing 185 ± 5 g were randomly selected from five groups: group I: orally administered with 1% Tween 80; group II: administered with 1 g paracetamol; group III: administered with 1 g paracetamol and 50 mg morin; group IV: administered with 100 mg paracetamol and morin; and group V: administered with 100 mg paracetamol and silymarin, with all treatments administered for 14 days. Results: Morin and silymarin significantly protected the rats against induced alterations in the plasma total cholesterol, triacylglycerol, and HDL-C levels as well as the liver ALT, AST, ALP, LDH, protein thiol, GSH, SOD, CAT, MDA, and tumor necrosis factor-alpha levels. Furthermore, morin significantly inhibited the expression of NF-κB, NADPH oxidase-2, and interleukin-6 and induction of heme oxygenase-1 compared with paracetamol. The histological results indicated that morin protected the liver tissues against the toxic effect of paracetamol. Conclusion: Morin significantly depletes the side effects of paracetamol and protects the liver tissue from the resulting free radicals.

Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress

Ziziphus abyssinica root bark is widely used in folk medicine to manage liver diseases, particularly, jaundice but its effect on paracetamol-induced liver toxicity (PILT) has not yet been validated. This study explored the ameliorative effect of ethanolic root bark extract of Ziziphus abyssinica (ZAE) against PILT in rats. The flavonoid and phenolic content of ZAE was evaluated using Folin-Ciocalteau and aluminium trichloride colorimetric methods, respectively. Antioxidant activity of ZAE was determined in vitro by evaluating its ferrous reducing antioxidant capacity (FRAC) as well as DPPH and nitic oxide (NO) radicals scavenging activities. Sprague-Dawley rats were assigned to six groups (n = 6) and administered with normal saline (10 mL/kg, p.o.), N-acetylcysteine (50 mg/kg, i.p.) and ZAE (30, 100, and 300 mg/kg, p.o.) respectively for seven days after which they received paracetamol (PCM, 3000 mg/kg, p.o.). Animals were sacrificed 48 h after paracetamol administration under light anaesthesia and assessed for liver toxicity and oxidative stress. Total flavonoid and phenolic contents of ZAE were 1313.425 µg/mL quercetin equivalence and 268.31 µg/mL gallic acid equivalence respectively. ZAE exhibited marked FRAC as well as DPPH and NO radical scavenging activities with IC50s of 80.41 ± 1.56, 67.56 ± 1.11 and 7.11 ± 1.48 μg/mL respectively. ZAE and N-acetylcysteine significantly (p < 0.05) reduced the paracetamol-mediated elevation of serum total bilirubin, proteins and activity of liver enzymes (AST, ALP, and ALT). Similarly, ZAE increased hepatic glutathione, total thiols and catalase activity of the paracetamol intoxicated rats. Morphological changes associated with the paracetamol hepatotoxicity were also ameliorated by ZAE. Overall, the hepatoprotective effect of ZAE may be related to its antioxidant property.

Phytochemical Analysis and Hepatoprotective Activity of Elytraria acaulis

Introduction: The emerging of new diseases, resistance to contemporary using drugs and inadequate usage of commonly available drugs leading to different side effects and sometimes to mortality. So, there is need to identify efficient drugs from easily available sources. Traditional medicines from medicinal plants have been using since ancient times to treat different diseases, are easily available herbal formulations and there were still many medicinal plants were unexplored about their therapeutic potentiality. So, the current research is aimed to explore phytochemical constituent and hepatoprotective potentiality of Elytraria acaulis on paracetamol-induced liver toxicity.&#x0D; Methodology: The root parts Elytraria acaulis were used for extraction through maceration procedure using hexane, ethyl acetate and hydro-alcoholic (70% ethanol). The dried extracts used for further for phytochemical analysis using standard procedures and evaluated liver protection on paracetamol-induced liver toxicity by estimating liver bio markable enzymes such as AST (SGOT), ALT (SGPT), ALP and total bilirubin levels.&#x0D; Results: Qualitative phytochemical screening of E. acaulis extracts revealed the presence of different phytochemical constituents like steroids, terpenoids, flavonoids, alkaloids, glycosides, phenols, tannins, saponins and carbohydrates in them. The hydroalcoholic extract has more flavonoid content i.e., 23.84±0.28 (mg/gm) than other two extracts. The tested three extracts of E. acaulis had showed concentration dependent hepatoprotective activity. Among three extracts hydro-alcoholic extract had more potentially compared to other two extracts. The percentage protection produced by the hydro-alcoholic extract on the enhancement of AST(SGOT), ALT (SGPT), ALP and total bilirubin levels were 21.54%, 21.94%, 21.20%, and 20.52%, 36.27%, 38.26%, 37.55% and 36.14%, 67.76%, 70.04%, 69.83% and 68.61% respectively.&#x0D; Conclusion: The Elytraria acaulis root extracts had showed significant biological activities and own different phytochemical constituents. The hydroalcoholic extract possess more phenolic, flavonoid contents and the same had showed more potentiality against liver toxicity. The current results offer vital information about the traditional medicinal value of it. The further research is valuable and is under progress in evaluation of different biological activities and isolation of individual bioactive molecules from E. acaulis.

Hepatoprotective Role of Virgin Coconut Oil and Neem Extract in Acetaminophen Induced Liver Toxicity

Aim: To study the comparative hepatoprotective effect of Virgin Coconut Oil (VCO) and Neem (Azadirachta indica) leaf extract in acetaminophen (Paracetamol) induced liver toxicity. Methods: About 60 mixed population of rats (male/female) of Wistar and Sprague-Dawley species were randomly selected for the proposed study and are segregated into four equal groups. Every group contains 15 animal subjects. Group A was the control group given normal diet. In Group B, the rats were treated with a single dose of 2gm / kg body weight paracetamol, orally. Simultaneously, Group C were given an oral Neem extract of 500mg/kg body weight for 2 weeks days in combination with single dose of Paracetamol, while Group D were provided with 6.7ml/Kg/body weight Virgin Coconut Oil (VCO) for 15 days. Data was analyzed using SPSS Version 20.0 with level of significance being kept at p-value ≤0.05. Results: The mean values of ALT were 23.1, 100.5, 29.85, and 31.09 U/L in Group A, B, C, and D respectively. While, the mean values of AST were 25.6 U/L (Group A), 41 U/L (Group B), 19.3 U/L (Group C), and 15.2 U/L (Group D). The ALP showed maximum response indicated by the mean values of 221 U/L, 444 U/L, 241 U/L, and 243 U/L in Group A, B, C, and D respectively. Group B suggested the paracetamol induced liver toxicity indicated by the increase in hepatic DMEs right after the acetaminophen induction. Conclusion: Azadirachta Indica and Virgin Coconut Oil displayed hepatoprotective effects on the Wistar and Sprague-Dawley rats that were subjected to Paracetamol. Keywords: hepatic, Drug Metabolizing enzymes, Acetaminophen, Virgin coconut oil, Neem extract, Paracetamol, Wistar

Effects of nerol on paracetamol-induced liver damage in Wistar albino rats

Nerol, a monoterpene is evident to possess diverse biological activities, including antioxidant, anti-microbial, anti-spasmodic, anthelmintic, and anti-arrhythmias. This study aims to evaluate its hepatoprotective effect against paracetamol-induced liver toxicity in a rat model. Five groups of rats (n = 7) were orally treated (once daily) with 0.05% tween 80 dissolved in 0.9% NaCl solution (vehicle), paracetamol 640 mg/kg (negative control), 50 mg/kg silymarin (positive control), or nerol (50 and 100 mg/kg) for 14 days, followed by the hepatotoxicity induction using paracetamol (PCM). The blood samples and livers of the animals were collected and subjected to biochemical and microscopical analysis. The histological findings suggest that paracetamol caused lymphocyte infiltration and marked necrosis, whereas maintenance of the normal hepatic structural was observed in group pre-treated with silymarin and nerol. The rats pre-treated with nerol significantly and dose-dependently reduced the hepatotoxic markers in animals. Nerol at 100 mg/kg significantly reversed the paracetamol-induced altered situations, including the liver enzymes, plasma proteins, antioxidant enzymes and serum bilirubin, lipid peroxidation (LPO) and cholesterol [e.g., total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c)] levels in animals. Taken together, nerol exerted significant hepatoprotective activity in rats in a dose-dependent manner. PCM-induced toxicity and nerol induced hepatoprotective effects based on expression of inflammatory and apoptosis factors will be future line of work for establishing the precise mechanism of action of nerol in Wistar albino rats.

Sulfate conjugation may be the key to hepatotoxicity in paracetamol overdose.

Paracetamol-induced hepatotoxicity is the leading cause of acute liver failure in many countries, including North America and the United Kingdom. Among the three dominant paracetamol metabolism pathways (i.e. glucuronidation, sulfation and oxidation), the importance of sulfation is often underestimated because of the general thinking that the sulfation pathway is saturated at therapeutic doses and ultimately accounts for a limited proportion of the fate of a paracetamol dose. We illustrate that insufficient sulfation leads to a shift in biotransformation of paracetamol to toxic oxidation pathways and patients with low sulfate reserves are at higher risk of paracetamol toxicity. Here, we propose that sulfation is of critical importance in understanding the risk of liver toxicity secondary to paracetamol overdose. Serum inorganic sulfate, a measurable substrate on the causal path of paracetamol-induced liver toxicity, should be considered a biomarker for potential toxicity as well as a target for treatment.

In vivo antioxidant and hepatoprotective activity of ethanol leaf extract of Senna hirsuta Mill

Purpose: Liver diseases as a problem all over the world has led to many deaths because the conventional drugs known for the cure are inadequate to effect perfect healing. This study aims to evaluate the in vivo antioxidant and hepatoprotective potentials of ethanol leaf extract of Senna hirsuta using mice model.Methods: After the initial effect of hepatic injury in mice with 1 g/kg body weight of paracetamol in a single dose for three days, 200, 400, 800, 1000 and 2000 mg/kg body weight of extract concentrations were used for treating the mice for five days. Blood and liver tissue samples were collected for analysesResults: The results obtained proved that paracetamol elicited toxicity in the mice. The red blood cells mean count in the negative control (7.67±0.92 million/mm3) was higher than the values obtained from the positive control (4.36±0.12 million/ mm3). The WBC mean values of 3.50±0.18 thousand/mm3 from negative control were lower than the positive control group (9.62±0.39 thousand/ mm3). Also, a higher value above the permissible level (11-19 %) was obtained in the haemoglobin estimation of the positive control (20.11%) than the negative control (11.50%). Values of the positive control and extract treated were higher than the negative control value while lower values were recorded in GSH and CAT in positive control and extract treated. Higher biochemical values were recorded in the positive control, and the extract administered except for albumin and protein. However, the injuries caused that manifested in the mice haematology, biochemical and liver disorders were significantly improved with the 200 – 2000 mg of extract concentrations.Conclusion: Leaf extract of Senna hirsuta proved the hepatoprotective activity of the employed extracts. The observation did by biochemical, hematological indices, and recovery improvement in liver function by histologic findings. Therefore, established that S. hirsuta ethanol leaf extract has hepatoprotective affinity over paracetamol-induced liver toxicity.

Assessment of antioxidant traits and protective action of Egyptian acacia pods extracts against paracetamol-induced liver toxicity in rats.

This study investigates the protective effect of Egyptian acacia pod extracts against overdose of paracetamol-induced liver damage. Egyptian acacia green and brown pods were extracted by mixture of ethanol 80%: HCl (6M) (99:1 v/v). In extracts of green and brown pods, total phenolic content in hydrolyzed ethyl acetate fraction (HEF) at pH 4, was 649.89 and 712.14mg GAE/g while antioxidant activity was 95.55% and 97.35%, both being the highest than any fraction. HEF (pH 4) in brown pods was analyzed by HPLC, there were 22 phenolic compounds rich in ethyl vanillin about 227mg/g and 11 flavonoids rich in catechin 48.70mg/g. A biological experiment was conducted using HEF (pH4) in brown pods against overdose of paracetamol in albino rats induced to hepatotoxicity. Thirty rats were divided into five groups; a control group, a paracetamol group, and the other three received paracetamol plus silymarin or two doses of HEF. Animals were received paracetamol and treated with either silymarin or HEF showed reduced levels of liver (ALT, AST, and ALP) and kidney (urea, creatinine, and uric acid) markers compared with the control group as well as reduction of oxidative stress and increment antioxidant enzyme activity in liver tissue when compared with the paracetamol group. It could be concluded that both HEF and silymarin are considerably high hepatoprotector against paracetamol-induced hepatotoxicity in rats due to their strong antioxidant activity. PRACTICAL APPLICATIONS: Both HEF and silymarin improved liver functions and exerted strong antioxidant activities. This antioxidant activity would have a positive effect against oxidative liver damage caused by parcetamol. Thus, it may be concluded that the liver plasma membranes were protected and the regenerative and reparative capacity of liver by phenolic compound in HEF treatment. The study demonstrated the HEF hepatoprotective activity and recommends using Egyptian acacia pods for treatment of liver disorders.

PHYTOCHEMICAL ANALYSIS, ANTIOXIDANT AND HEPATOPROTECTIVE ACTIVITY OF ACTINIOPTERIS RADIATA

Objective: The medicinal plants have been using to treat ailments since ancient times. The recent advances in science and technology impel humans to evaluate medicinal plants therapeutic efficiency and isolation of bioactive compounds in pure forms before their use in development of new drugs and their derivatives. But even now, abundant medicinal plants unevaluated scientifically. The current study was aimed to explore phytochemical constituents, antioxidant and hepatoprotective activities of Actiniopteris radiata root parts.&#x0D; Methods: Standard procedures have been used to perform phytochemical analysis. Antioxidant activity was carried using In vitro methods on superoxide, hydroxyl, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. Hepatoprotective activity was studied by paracetamol-induced liver toxicity on WISTAR albino rats. The parameters assessed were Aspartate aminotransferase (SGOT/AST), Alanine aminotransferase (SGPT/ALT), alkaline phosphatase (ALP) and total bilirubin levels.&#x0D; Results: The tested extracts (hexane, ethyl acetate, and hydro-alcoholic) possess biologically active compounds such as sterols, terpenoids, glycosides, phenolics, alkaloids, flavonoids. The hydro-alcoholic extract has more phenolic contents (24.28±0.3) and flavonoid contents (22.68±0.6). The extracts showed dose dependent activity on tested free radicals and extracts showed more percentage inhibition at 320µg. The hydro-alcoholic extract showed more percentage inhibition i.e. 71.00±2.08 on DPPH free radical, 79.67±1.20 on hydroxyl free radical and 80.33±1.20 on superoxide free radical. As antioxidant activity of hexane and ethyl acetate extracts was less and they also showed less percentage protection on liver toxicity, hydro-alcoholic extract showed more percentage protection on biomedical enzyme levels of liver toxicity at high concentration i.e., 400 mg/kg b.w. The percentage protection on the enhancement of AST (SGOT), ALT (SGPT), ALP, and total bilirubin levels were 82.24%, 82.14%, 84.18%, and 82.85% are significant (P&lt;0.01) as Liv52 shown percentage protection on the enhancement of Aspartate aminotransferase (SGOT), alanine aminotransferase (SGPT), Alkaline phosphatase (ALP) and total bilirubin levels were 93.58%, 92.83%, 94.67% and 93.57%.&#x0D; Conclusion: The current study was aimed to explore phytochemical constituents, antioxidant and hepatoprotective activities of Actiniopteris radiata root parts extracts. The outcome of the current research results provides scientific evidence of the traditional usage of Actiniopteris radiata.

A systems toxicology paracetamol overdose framework: accounting for high-risk individuals

The most commonly prescribed painkiller worldwide, paracetamol (acetaminophen, APAP) is also the predominant cause of acute liver failure (ALF), and therefore paracetamol-induced liver toxicity remains an important clinical problem. The standard clinical treatment framework for paracetamol overdose currently allows for antidote therapy decisions to be made based on a nomogram treatment line. This treatment threshold is lowered for patients adjudged to be highly susceptible to liver injury due to risk factors such as anorexia nervosa or bulimia. Additionally, both the original and adjusted clinical frameworks are highly dependent on knowledge from the patient regarding time since ingestion and initial dose amount, both of which are often highly unpredictable. We have recently developed a pre-clinical framework for predicting time since ingestion, initial dose amount and subsequent probability of liver injury based on novel biomarker concentrations. Here, we use identifiability analysis as a tool to increase confidence in our model parameter estimates and extend the framework to make predictions for both healthy and high-risk populations. Through pharmacokinetic-pharmacodynamic model refinement, we identify thresholds that determine whether necrosis or apoptosis is the dominant form of cell death, which can be essential for effective ALF interventions. Using a single blood test, rather than the multiple tests required in the current clinical frameworks, our model provides overdose identification information applicable for healthy and high-risk individuals as well as quantitative measures of estimated liver injury probability.

Cytotoxic, hepatoprotective and antioxidant activities of Silybum marianum variety albiflorum growing in Egypt

Silymarin prepared from the fruits of Silybum marianum (L.) Gaertn. (Asteraceae) has long been used for the treatment of liver disorders. This study was carried out to evaluate the protective effect of the fruit extract of white-flowered S. marianum variety albiflorum Eig. (WSE) against paracetamol–induced liver toxicity in rats. Silyhermin, isosilandrins A/B were identified as the major flavonolignans in WSE. Cytotoxic activities of WSE and isolated flavonolignans compared to silymarin were carried out using sulforhodamine B assay. WSE, silyhermin and isosilandrins had no obvious harmful effect on normal human cell line compared to silymarin with IC50 values 78.95, 84.34, 72.14 and 16.83 µg/ml, respectively. The hepatoprotective activity of WSE at dose 50 mg/kg was comparable to silymarin (100 mg/kg). These data were supplemented with histopathological studies on liver sections. The hepatoprotective effects of WSE on oxidative stress induced by administration of paracetamol are probably associated with its antioxidant properties.