Hepatotoxicity In Rat Model Research Articles

Potential therapeutic effect of Thymoquinone on Cisplatin-induced hepatotoxicity in rats

Aim: Cisplatin (CIS), an antineoplastic agent, shows serious side effects such as hepatotoxicity. Thymoquinone (ThQ) is a powerful anti-oxidant with many beneficial effects such as anti-inflammatory, anti-tumoral. The aim of this study was to investigate whether ThQ treatment has hepatoprotective effect in CIS-induced hepatotoxicity model in rats and also to determine how CIS and/or ThQ treatments affect OTULIN levels, one of the deubiquitinases, in liver tissue. Materials and Methods: The 28 rats used in the study control (application not done), CIS (7 mg/kg CIS, first day of experiment, intraperitoneal), CIS+ThQ (7 mg/kg CIS, first day of experiment, intraperitoneal + 10 mg/kg/day ThQ, oral gavage) and ThQ (10 mg/kg/day ThQ, oral gavage) were divided into four equal groups (n=7). The experiment was terminated upon completion of all applications (day 15). The effects of CIS and\or ThQ apps on liver tissues were examined biochemically, histopathologically and immunohistochemically. Results: CIS application increased liver enzyme levels, histopathological changes, inflammation, oxidative stress and apoptosis in liver tissue and caused a decrease in OTULIN level. However, ThQ administration showed a positive regulatory effect on CIS-induced changes in liver tissue. Conclusion: ThQ supplementation has a hepatoprotective effect against CIS-induced liver tissue damage.

"Insights From a Rat Model of Paracetamol-Induced Hepatotoxicity into the Molecular Mechanisms of Silymarin and Resveratrol Combination Therapy for Protecting Liver Function"

"Insights From a Rat Model of Paracetamol-Induced Hepatotoxicity into the Molecular Mechanisms of Silymarin and Resveratrol Combination Therapy for Protecting Liver Function"

Dapagliflozin alleviates arsenic trioxide-induced hepatic injury in rats via modulating PI3K/AkT/mTOR, STAT3/SOCS3/p53/MDM2 signaling pathways and miRNA-21, miRNA-122 expression

Dapagliflozin (DPG) is a sodium-glucose co-transporter 2 inhibitor that is commonly used in the treatment of type 2 diabetes. However, studies have shown that DPG has a protective effect under a variety of experimental conditions through its antioxidative and anti-inflammatory properties. DPG's effect on experimental hepatotoxicity caused by arsenic trioxide (ATO) has yet to be investigated. The purpose of this study was to investigate the protective effect of DPG in preventing hepatic damage caused by ATO and discover the underlying mechanisms. The effect of DPG (1 mg/kg, orally) on ATO (5 mg/kg, i.p.)-induced hepatic injury was evaluated in rats. Serum liver function parameters, as well as oxidative stress biomarkers and inflammatory cytokine levels were assessed. Histopathological changes in the liver were detected using H&E staining. Using Western blotting and PCR techniques, the molecular mechanisms of DPG in ameliorating hepatic injury were investigated. DPG improved liver function by inhibiting histopathological changes, decreasing levels of hepatic function and toxicity parameters measured in both serum and tissues, and exhibiting antioxidant and anti-inflammatory effects, according to the findings. Consistent with the PCR results, DPG also decreased the expression of LC3-II, micro-RNA-122, and micro-RNA-21 while increased the expression of SOCS3. Furthermore, according to western blotting results, DPG was able to reduce the protein expression of AKT, mTOR, PI3K, and STAT3. Although further clinical research is necessary, this study highlights the potential of DPG in preventing liver damage in a rat model of hepatotoxicity induced by ATO.

The possible protective role of platelet-rich plasma against cisplatin-induced hepatotoxicity in rat model

The possible protective role of platelet-rich plasma against cisplatin-induced hepatotoxicity in rat model

Hepatoprotective effects of almond shells against carbon tetrachloride induced liver injury in albino rats

Liver injury is a prevalent pathological process that can give rise to conditions such as fatty liver, cirrhosis, fibrosis, and even cancer. It has been observed that plants and natural products possess significant protective effects against liver injury. Current study was performed to investigate the efficacy of almonds shell against carbon tetrachloride (CCl4) induced hepatotoxicity in rat model. As almonds shell contain a large variety of phenolic and flavonoid compounds, which are largely associated with antioxidant and hepatoprotective properties. For this purpose, screening of small-scale library of twenty plant extracts was performed for evaluation of antioxidant potential by DPPH assay. The data revealed that almonds shell extract (ASEE) exhibited potent antioxidant activity. This potent extract was further evaluated for hepatoprotective activity in in vivo rat model on 30 rats, divided into 6 groups of 5 rats each. On 29th day all rats were sacrificed and blood serum was collected for further analysis. Liver tissues were also preserved in formalin for histopathology. The results demonstrated that ASEE displayed a protective effect on liver function tests (LFT), renal function tests (RFT), and lipid biomarkers in comparison to the CCl4 group. The histological data also unveiled a substantial safeguarding impact on liver damage, characterized by a reduction in apoptosis, diminished liver hemorrhage, and decreased accumulation of cellular debris. The data indicates that ethanolic extract from almond shells possesses hepatoprotective potential, suggesting its viability as an alternative source for hepatoprotective drug development after pre-clinical research.

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.

In Vitro/In Vivo Hepatoprotective and Antioxidant Effects of Defatted Extract and a Phenolic Fraction Obtained from Phlomis Tuberosa.

An in vitro/in vivo hepatotoxicity and hepatoprotection evaluation of a defatted extract and a phenolic fraction from Phlomis tuberosa, administered alone and in a carbon tetrachloride (CCl4)-induced metabolic bioactivation model, was performed. The extract and the phenolic fraction were analysed by high performance liquid chromatography (HPLC) to determine the total flavonoid content, to identify flavonoids and to quantify verbascoside. In addition, total polyphenolics in the samples were expressed as gallic acid equivalents. Applied alone, the extract and the fraction (5, 10 and 50 µg/mL) did not show a statistically significant hepatotoxic effect on isolated rat hepatocytes in vitro. In a CCl4-induced hepatotoxicity model, the samples exhibited a concentration-dependent, statistically significant hepatoprotective effect, which was most pronounced at 50 µg/mL for both. The phenolic fraction exhibited a more pronounced hepatoprotective effect compared to the extract. Data from the in vitro study on the effects of the extract were also confirmed in the in vivo experiment conducted in a CCl4-induced hepatotoxicity model in rats. A histopathological study showed that the animals treated with CCl4 and the extract had an unaltered histoarchitecture of the liver. The effects of the extract were the same as those of silymarin.

Stabilization of glutathione redox dynamics and CYP2E1 by green synthesized Moringa oleifera-mediated zinc oxide nanoparticles against acrylamide induced hepatotoxicity in rat model: Morphometric and molecular perspectives.

The terrible reality is that acrylamide (AA) is a common food contaminant found in a wide variety of commonly consumed foods. This research involves the advancement of a more dependable technique for the bio-fabrication of zinc oxide nanoparticles (ZNPs) through the green method using Moringa Oleifera extract (MO-ZNPs) as an efficient chelating agent for acrylamide (AA). The effects of AA on glutathione redox dynamics, liver function, lipid profile, and zinc residues in Sprague Dawley rats are investigated. Finally, the microarchitecture and immunohistochemical staining of Caspase-3 and CYP2E1 were determined in the liver tissue of rats. Four separate groups, including control, MO-ZNPs (10mg/kg b. wt), AA (20mg/kg b. wt), and AA+MO-ZNPs for 60 days. The results revealed a suppressed activity of glutathione redox enzymes (GSH, GPX,and GSR) on both molecular and biochemical levels. Also, AA caused elevated liver enzymes, hepatosomatic index, and immunohistochemical staining of caspase-3 and CYP2E1 expression. MO-ZNPs co-treatment, on the other hand, stabilized glutathione-related enzyme gene expression, normalized hepatocellular enzyme levels, and restored hepatic tissue microarchitectures. It could be assumed that MO-ZNPs is a promising hepatoprotective molecule for alleviating AA-induced hepatotoxicity. We witnessed changes in glutathione redox dynamics to be restorative. Glutathione and cytochrome P450 2E1 play crucial roles in AA detoxification, so maintaining a healthy glutathione redox cycle is necessary for disposing of AA toxicity.

Scutellarein regulates the PTEN/AKT/NFκB signaling pathway to reduce pirarubicin related liver inflammation.

The side effects of chemotherapy drugs have been hindering the progress of tumor treatment. The liver is the metabolic site of most drugs, which leads to the frequent occurrence of liver injury. Classical chemotherapy drugs such as pirarubicin (THP) can also cause dose‑dependent hepatotoxicity, and the related mechanism is closely related to liver inflammation. Scutellarein (Sc) is a potential Chinese herbal monomer exhibiting liver protection activity, which can effectively alleviate the liver inflammation caused by obesity. In the present study, THP was used to establish a rat model of hepatotoxicity, and Sc was used for treatment. The experimental methods used included measuring body weight, detecting serum biomarkers, observing liver morphology with H&E staining, observing cell apoptosis with TUNEL staining, and detecting the expression of PTEN/AKT/NFκB signaling pathways and inflammatory genes with PCR and western blotting. However, whether Sc can inhibit the liver inflammation induced by THP has not been reported. The experimental results showed that THP led to the upregulation of PTEN and the increase of inflammatory factors in rat liver, while Sc effectively alleviated the aforementioned changes. It was further identified in primary hepatocytes that Sc can effectively inhabited PTEN, regulate AKT/NFκB signaling pathway, inhibit liver inflammation and ultimately protect the liver.

Protective effect of Allium scorodoprasum L. ethanolic extract in cyclophosphamide-induced hepatotoxicity model in rats.

Cyclophosphamide is a chemotherapeutic agent and immunosuppressant drug; however, it damages the liver. This study investigates the protective effect of ethanolic extract of Allium scorodoprasum (ASE) on cyclophosphamide-induced liver injury. Twenty-eight Wistar albino rats were randomly divided into four groups (n = 7 per group): healthy rats, cyclophosphamide (200 mg/kg), cyclophosphamide (200 mg/kg) + ASE (100 mg/kg) and cyclophosphamide (200 mg/kg) + ASE (200 mg/kg). ASE was administered for 14 days, and the rats were euthanized 24 h after cyclophosphamide administration. Cyclophosphamide treatment leads to an increase in serum levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, total cholesterol, triglycerides, low-density lipoprotein and very low-density lipoprotein, as well as an increase in the liver levels of malondialdehyde, tumour necrosis factor, interleukin (IL)-1β and IL-6, while high-density lipoprotein levels decrease. Treatment with cyclophosphamide caused liver necrosis and postnecrotic cell infiltration; however, pathological changes were prevented by ASE. 8-Hydroxy-2'-deoxyguanosine, anti-4-hydroxynenal antibody and anti-dityrosine levels increased in rats treated with cyclophosphamide and decreased in the groups treated with ASE. These changes were dose dependent in the ASE-treated groups. Treatment with cyclophosphamide caused liver damage due to oxidative stress and inflammation. ASE regulated the damage at high doses because it has potent antioxidant and anti-inflammatory ingredients. In future studies, it may be beneficial to administer ASE in higher doses or for longer periods of time.

Hepato-protective effects of Silymarin against methotrexate-induced hepatotoxicity in rat model

Hepato-protective effects of Silymarin against methotrexate-induced hepatotoxicity in rat model

Hepato-protective effects of Montelukast against methotrexate-induced hepatotoxicity in rat model

Hepato-protective effects of Montelukast against methotrexate-induced hepatotoxicity in rat model

Sulforaphane, an Nrf-2 Agonist, Modulates Oxidative Stress and Inflammation in a Rat Model of Cuprizone-Induced Cardiotoxicity and Hepatotoxicity

Cuprizone (CPZ) is a neurotoxic agent that is used to induce demyelination and neurotoxicity in rats. This study aimed to investigate the protective potential of sulforaphane (SF), nuclear factor E2 related factor (Nrf-2) activator, against CPZ-induced cardiotoxicity and hepatotoxicity. Male adult Wistar rats (n = 18) were fed with a regular diet or a CPZ-contained diet (0.2%) for four weeks. The rats were divided into three groups (n = 6): negative control rats, CPZ-exposed rats, and CPZ + SF treated rats. SF was intraperitoneally administrated (2 mg/kg/day) for two weeks. The anti-inflammatory and anti-oxidative functions of SF were investigated biochemically, histologically, and immunohistochemically. CPZ increased serum levels of cardiac troponin 1 (CTn1), aspartate amino transaminase (AST), alanine amino transaminase (ALT), and alkaline phosphatase (ALP). In addition, serum levels of inflammatory interferon-gamma (IFN-γ), and pro-inflammatory interleukin 1β (IL-1β) were significantly elevated. Moreover, CPZ administration provoked oxidative stress as manifested by declined serum levels of total antioxidant capacity (TAC), as well as, stimulated lipid peroxidation and decreased catalase activities in both cardiac and hepatic tissues. SF treatment reversed all these biochemical alterations through exerting anti-oxidative and anti-inflammatory activities, and this was supported by histopathological investigations in both cardiac and hepatic tissues. This SF-triggered modulation of oxidative stress and inflammation is strongly associated with Nrf-2 activation, as evidenced by activated immunoexpression in both cardiac and hepatic tissues. This highlights the cardioprotective and hepatoprotective activities of SF via Nrf-2 activation and enhancing catalase function.

Astragaloside IV Alleviates Atorvastatin-Induced Hepatotoxicity via AMPK/SIRT1 Pathway

Introduction: Atorvastatin (ATO) is often used to reduce blood lipids and prevent atherosclerosis, but excessive use of ATO will lead to hepatotoxicity. This paper investigated the effects of astragaloside IV (AS IV), which has multiple biological functions, on ATO-induced hepatotoxicity and the underlying mechanism. Methods: ATO treatment induced a rat model of hepatotoxicity, followed by AS IV treatment. Colorimetric kits were used to detect rat liver function indexes including aspartate aminotransferase (AST), alanine transaminase (ALT), malondialdehyde (MDA), and reduced glutathione (GSH). Reactive oxygen species (ROS) level was determined by 2′, 7′-Dichlorodihydrofluorescein diacetate kit. The liver fibrosis and F4/80 expression were detected by Sirius red staining and immunochemistry. Mitochondrial electron transport chain complex I and complex IV activities were examined. The level of mitochondrial membrane potential (MMP) was detected by JC-1 staining. The inflammatory factor levels were detected by quantitative real-time polymerase chain reaction. Western blot detected apoptosis-related proteins and AMPK/SIRT1-related proteins. Results: ATO increased ALT, AST, MDA, and ROS levels and decreased GSH content but was subsequently reversed by AS IV. AS IV alleviated liver tissue damage caused by ATO. AS IV elevated complex I and complex IV activity and promoted MMP levels in ATO rats. ATO promoted inflammatory factor release in SD rats but was then suppressed by AS IV. AS IV inhibited Bax, cleaved caspase-3 but up-regulated Bcl-2 in ATO-induced rats. ATO inhibited SIRT1 expression and AMPK phosphorylation, which was subsequently promoted by AS IV. Conclusion: AS IV inhibits ATO-induced hepatotoxicity by activating the AMPK/SIRT1 pathway.

Uroprotective and Hepatoprotective Potential of Anagallis arvensis against the Experimental Animal Model.

Anagallis arvensis (A. arvensis) belonging to the family Primulaceae is traditionally used for liver and kidney diseases. The aim of the study was to evaluate the uroprotective and hepatoprotective potentials of A. arvensis in cyclophosphamide-induced interstitial cystitis and paracetamol-induced hepatotoxicity rat model, respectively. Nociception, bladder weight, vesical vascular permeability, Gray's criteria for edema and hemorrhage, and levels of nitric oxide, catalase, and glutathione were estimated and studied in the cystitis model. Liver function test, lipid profile, and histopathological evaluation were carried out in the hepatoprotective activity. Oral administration of methanol extract of A. arvensis significantly reduced bladder weight, vesical vascular permeability, edema, hemorrhage, nitric oxide, IL-6, and TNF-α, while the level of catalase and glutathione peroxide was increased. In hepatoprotective activity, pretreatment with A. arvensis significantly decreased the level of liver markers (Bilirubin, ALT, AST, and ALP) and lipid profile (cholesterol, TG, LDL, and VLDL). Histopathological studies confirmed the biochemical findings of both studies. GC-MS analysis presented the presence of antioxidant phytoconstituents. Thus, it was concluded that A. arvensis might act as uroprotective and hepatoprotective due to the presence of antioxidant phytochemicals in the rodent model. Isolation and identification of phytochemicals present in the methanol extract of A. arvensis and evaluation of their exact mechanism of action become mandatory in future studies.

Schisandrin B Diet Inhibits Oxidative Stress to Reduce Ferroptosis and Lipid Peroxidation to Prevent Pirarubicin-Induced Hepatotoxicity.

Objective Pirarubicin (THP) is one of anthracycline anticancer drugs. It is widely used in the treatment of various cancers, but its hepatotoxicity cannot be ignored. Schisandrin B (SchB) is a traditional liver-protecting drug, which has the ability to promote mitochondrial function and upregulate cellular antioxidant defense mechanism. However, whether it can resist THP-induced hepatotoxicity has not been reported. The purpose of this study was to observe and explore the effect of SchB on THP-induced hepatotoxicity and its potential mechanism by adding SchB to the diet of rats with THP-induced hepatotoxicity. Methods The rat model of THP-induced hepatotoxicity was established and partly treated with SchB diet. The changes of serum liver function indexes ALT and AST were observed. The histomorphological changes of liver were observed by HE staining. The biomarker levels of oxidative stress in rat serum and liver were measured to observe oxidative stress state. The expressions of ferroptosis-related protein GPX4 and oxidative stress-related protein were detected by Western blot. Primary hepatocytes were prepared and cocultured with THP, SchB, and Fer-1 to detect the production of reactive oxygen species (ROS) and verify the above signal pathways. Results THP rats showed a series of THP-induced hepatotoxicity changes, such as liver function damage, oxidative stress, and ferroptosis. SchB diet effectively alleviated these adverse reactions. Further studies showed that SchB had strong antioxidant and antiferroptosis abilities in THP-induced hepatotoxicity. Conclusion SchB has obvious protective effect on THP-induced hepatotoxicity. The mechanism may be closely related to inhibiting oxidative stress and ferroptosis in the liver.

Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin

Silymarin, a phyto-constituent derived from the plant Silybum marianum, has been widely acknowledged for its hepatoprotective activities. Nevertheless, its clinical utility is adversely hampered by its poor water-solubility and its limited oral bioavailability. The aim of this study was to investigate the efficacy of phospholipid-based phytosomes for enhancing the oral bioavailability of silymarin. The phytosomes were prepared using the solvent evaporation technique and were optimized using a full factorial design. The optimized silymarin phytosomal formulation was then characterized for particle size, surface morphology, aqueous solubility, and in vitro drug release. Furthermore, in vivo antioxidant activity, hepatoprotective activity and oral bioavailability of the optimized formula were investigated in a rat model. The prepared silymarin phytosomes were discrete particles with a porous, nearly smooth surface and were 218.4 ± 2.54 nm in diameter. In addition, the optimized silymarin phytosomal formulation showed a significant improvement in aqueous solubility (~360 µg/mL) compared to pure silymarin and manifested a higher rate and extent of silymarin release from the optimized formula in dissolution studies. The in vivo assessment studies revealed that the optimized silymarin phytosomal formulation efficiently exerted a hepatoprotective effect in a CCl4-induced hepatotoxicity rat model via restoring the normal levels of antioxidant enzymes and ameliorating cellular abnormalities caused by CCl4-intoxication. Most notably, as compared to pure silymarin, the optimized silymarin phytosomal formulation significantly improved silymarin oral bioavailability, as indicated by a 6-fold increase in the systemic bioavailability. Collectively, phytosomes might represent a plausible phospholipid-based nanocarrier for improving the oral bioavailability of phyto-constituents with poor aqueous solubility.

Attenuation of methotrexate induced hepatotoxicity by epigallocatechin 3-gallate

Methotrexate (MTX) is currently used as first-line therapy for autoimmune diseases like rheumatoid arthritis, psoriasis, and systemic lupus erythematous. However, its use is limited by its hepatotoxic potential. Epigallocatechin-3-gallate (EGCG), an abundant catechin present in tea possesses potent antioxidant activity and effectively ameliorates oxidative stress-related disorders. This study aimed to investigate the hepatoprotective influence of EGCG in a MTX-induced rat model of hepatotoxicity. Sprague Dawley rats pretreated with EGCG (40 mg kg−1 b.w., p.o.) were administered a single dose of MTX (20 mg kg−1 b.w., i.p.) and its hepatoprotective efficacy compared with folic acid (1 mg kg−1 b.w., i.p.). On day 10, blood samples were collected to determine plasma levels of aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH), while the livers were examined for histopathogical changes along with levels of oxidative stress measured in terms of myeloperoxidase (MPO) activity, protein carbonylation (PCO), lipid peroxidation (LPO), and activities of cellular enzymatic antioxidants – superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). MTX significantly increased the plasma levels of AST, ALT, ALP, and LDH, which were prevented by pretreatment with EGCG, and was corroborated by histopathology. Additionally, MTX-induced hepatic oxidative stress as measured by increased generation of MPO, enhanced PCO, LPO, and decreased activities of antioxidant enzymes was mitigated by pretreatment with EGCG. The amelioration of MTX-induced hepatotoxicity by EGCG endorsed the inclusion of an anti-oxidant during chronic administration of MTX.

Chenopodium album extract ameliorates carbon tetrachloride induced hepatotoxicity in rat model

Major objective of this study was to explore the protective effect of the methanolic extract of Chenopodium albumagainst carbon tetrachloride induced hepatotoxicity in rats. Chenopodium album has locally been used for multiple medicinal proposes. Methanolic extract of Chenopodium album (whole plant) was prepared with Soxhlet extractor and rotatory evaporator. Antioxidant activity of Chenopodium album was determined by DPPH free radical scavenging assay. Thirty Wister (albino) rats (150–200 g) were divided into six groups for the evaluation of hepatoprotective potential of different concentrations of Chenopodium album against carbon tetrachloride (1:1 CCl4: Olive oil) under the controlled laboratory conditions. Group-I rats were administrated with olive oil (Normal control), Group-II with CCl4 only, Group-III with Silymarin (positive control), Group-IV with Chenopodium album (100 mg/kg), Group-V with Chenopodium album (200 mg/kg) and Group-VI rats with Chenopodium album (300 mg/kg) for the period of 28 days. Serum was taken to determine the levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, cholesterol, triglyceride, creatinine and urea in the blood. Formalin stored tissues were examined for histopathological analysis. DPPH assay showed that Chenopodium album has the potential for reduction of oxidative stress. Chenopodium album minimized the levels of ALT (70 ± 8.68 U/L, 68.75 ± 8.38 U/L & 73.5 ± 10.28 U/L), AST (219.5 ± 19.16 U/L, 140.75 ± 13.35 U/L & 221.25 ± 13.33 U/L) and ALP (289.5 ± 28.21 U/L, 258 ± 11.12 U/L & 248.25 ± 4.03 U/L) at different concentrations (100 mg/kg, 200 mg/kg, 300 mg/kg respectively). Chenopodium album enhanced triglyceride level (64.75 ± 12.66 mg/dl at 200 mg/kg) as compared to CCl4 treated group (33.25 ± 1.26 mg/dl). Carbon tetrachloride elevated urea level (43.25 ± 6.6) was decreased by high dose of Chenopodium album (18 ± 8.17). Moreover, Chenopodium album also improved WBC level (9.69 × 103 /Cu.mr & 10.59 × 103 /Cu.mr at low and medium doses respectively), RBCs level (6.97 × 103 /Cu.mr) and hemoglobin level (13.95 G/dL, 13.467 G/dL & 14.05 G/dL at low, medium and high doses). In vivo study of Chenopodium album methanolic extract demonstrates the potential for protection of liver and after pre-clinical studies the plant can be used as a safe alternative of commercially available hepatoprotective medicines.

Ameliorative effect of ethanolic extract of Limnophila rugosa (Scrophulariaceae) in paracetamol- and carbon tetrachloride-induced hepatotoxicity in rats

BackgroundLimnophila rugosa (Scrophulariaceae) is a perennial aquatic plant used as a diuretic and digestive tonic as well as in the treatment of diarrhea, dysentery, dyspepsia and urinary ailments. Genus Limnophila has been reported as hepatoprotective. The present study was undertaken to evaluate the hepatoprotective activity of the ethanolic extract of L. rugosa aerial part in paracetamol- and carbon tetrachloride-induced (CCl4) hepatotoxicity in albino Wistar rats. Ethanolic extract was subjected to high-performance liquid chromatography (HPLC) analysis for the estimation of phenolic and flavonoid compounds and gas chromatography–mass spectrometry (GC–MS) analysis for phytochemical analysis. The in vitro antioxidant activity was carried out by 2,2-diphenyl-1-picrylhydrazyl, nitric oxide radical and hydrogen peroxide assay. Hepatoprotective potential of L. rugosa was studied in paracetamol (750 mg/mg)- and CCl4 (1.25 ml/kg)-induced liver damage in albino rats at dose 200 and 300 mg/kg using silymarin (100 mg/kg) as standard. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) were determined in liver tissue homogenate. Serum biochemical and histopathological examination was performed. Molecular docking analysis was performed to understand the molecular mechanism of hepatoprotective activity.ResultsHPLC analysis revealed predominance of rutin. GC–MS analysis revealed camphor as principal component. Ethanolic extract exhibited significant concentration-dependent scavenging efficacy. The altered biochemical chemical parameters: aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, albumin, globulin and total protein, were significantly improved at 200 and 300 mg/kg in experimental rats. Extract signified hepatoprotective by decreasing lipid peroxidation and upregulating SOD, CAT and GSH. The findings were well supported by histological analysis. 2-Butyl-2, 7-octadien-1-ol (-5.8) and camphor (-4.8) gave the highest docking score on the transforming growth factor-β1.ConclusionsThe ameliorative effect of L. rugosa in the rat model of hepatotoxicity could be attributed to its antioxidant potential and bioactive principles such as betulin, 5-hydroxy-6,7,4′-trimethoxyflavone (salvigenin), betulinic acid, ursolic acid, 3-octanol, acetophenone, anisylacetone, caryophyllene, cis-anethole and the compounds camphor and 2-butyl-2,7-octadien-1-ol identified from GC–MS analysis.