Search Results (37)

Background: Liver diseases are a global health issue with an annual mortality of 80,000 patients, mainly due to complications that arise during disease progression, as effective treatments are lacking. Objectives: This study evaluated the hepatoprotective effects of two derivatives of cinnamic acid, LQM717 and LQM755, in a murine model of acute liver damage induced by carbon tetrachloride (CCl_4, 4 g/kg, single dose p.o.). Methods: Male Wistar rats were pretreated with five doses of LQM717 (20 mg/kg i.p.) or LQM755 (equimolar dose), starting 2 days before inducing hepatotoxic damage with CCl₄. Results: The key parameters of hepatocellular function and damage showed significant increases in ALT, ALP, GGT, and total and direct bilirubin in rats intoxicated with CCl₄, with decreased liver glycogen and serum albumin. Macroscopic and microscopic liver examinations revealed reduced inflammation, necrosis, and steatosis in animals pretreated with LQM717 or LQM755. Hepatomegaly was observed only in the LQM717 + CCl₄ group. LQM755 statistically provided partial protection against increases in ALT and ALP and completely prevented elevations in GGT and total and direct bilirubin. LQM755 completely prevented albumin reduction, while LQM717 only partially prevented it. Both compounds partially prevented glycogen depletion. Bioinformatic analysis identified 32 potential liver protein targets for LQM717 and 36 for LQM755. Conclusions: These findings suggest that LQM717 and LQM755 have significant hepatoprotective effects against CCl₄-induced acute liver injury, providing information for future studies in other acute and chronic models, as well as to elucidate their mechanisms of action. Full article

The transformative effect of nanotechnology is revolutionizing medicine by introducing new therapeutic approaches. This study explores the utilization of aqueous extract from mushroom (Cortinarius sp.) used as a reducing agent to prepare zinc oxide myco-nanoparticles (ZnO-MNPs) in an eco-friendly manner. The synthesis of ZnO-MNPs has been confirmed by various characterization studies, including UV-vis spectroscopy, which revealed an absorption peak at 378 nm; X-ray diffraction (XRD) analysis, which revealed a wurtzite hexagonal structure; and Fourier transform infrared spectra (FTIR), which showed stabilizing agents around the ZnO-MNPs. The effectiveness of ZnO-MNPs as an anti-cancer agent was evaluated by monitoring liver biochemical parameters against hepatotoxicity caused by carbon tetrachloride (CCl₄) in Balb C mice. The results showed that the levels of catalase, glutathione (GSH), and total protein were significantly lower, while alanine aminotransferase (ALT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), melanin dialdehyde (MDA), and total bilirubin (TB) were significantly higher in each of the CCl₄ treatment groups. ZnO-MNP treatment significantly reduced the toxicological effects of CCl₄ but did not completely restore the accumulation. The antimicrobial efficacy of ZnO-MNPs was investigated and showed potential results against common pathogens, including Bacillus subtilis (29.05 ± 0.76), Bacillus meurellus (27.05 ± 0.5), Acetobacter rhizospherensis (23.36 ± 0.5), and Escherichia coli (25.86 ± 0.80), while antifungal activity was relatively lower. Moreover, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that ZnO-MNPs are strong antioxidant agents. Overall, these findings highlight the effectiveness of myco-synthesized ZnO-NPs in combating pathogenic diseases, their promising role in cancer therapy, and their potential as a biomaterial option for future therapeutic applications. Full article

Abroma augustum (L.) L. f. is characterized by its fibrous structure, spiny trichomes, and distinctive leaf formations, which collectively contribute to its unique morphology and potential medicinal applications. This study aims to investigate the phytochemical constituents and elucidate the pharmacognostic and physicochemical characteristics of the stem bark powder, including evaluation of its antioxidant capacity and hepatoprotective effects against carbon tetrachloride (CCl₄)-induced hepatotoxicity in both in vitro and ex vivo experimental models. Comprehensive phytochemical screening identified 50 distinct phytochemicals, including a range of alkaloids, flavonoids, terpenes, phenolics, and coumarins, among others. The extract displayed substantial solubility, with total phenolic and flavonoid content quantified as 12.32 ± 0.01 mg/g and 42.14 ± 3.5 mg/g, respectively. The antioxidant activity revealed IC₅₀ values obtained from 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), measured at 214.007 µg/mL, 132.307 µg/mL, and 45.455 µg/mL, respectively. Additionally, the methanolic extract exhibited significant hepatoprotective properties, with observable reductions in lipid peroxidation and decreased concentrations of liver damage biomarkers (ALT, AST, and LDH) in both HepG2 cells and goat liver homogenate. Future investigations are warranted to elucidate the underlying mechanisms of these effects, including histopathological examinations and biochemical assays, followed by the administration of plant methanolic extracts. Full article

The effect of dark deprivation on the morphofunctional state and rhythmostasis of the liver under CCl₄ toxic exposure has been studied. The relevance of this study is due to the fact that the hepatotoxic effect of carbon tetrachloride on the liver is well studied, but there are very few data on the relationship between CCl₄ intoxication and circadian biorhythms, and most of the studies consider the susceptibility of the organism in general and of the liver in particular to the influence of CCl₄ in some separate periods of the rhythm, but not the influence of this chemical agent on the structure of the whole rhythm. In addition, earlier studies indicate that light disturbance causes certain changes in the morphofunctional state of the liver and the structure of the circadian rhythm of a number of parameters. As a result of this study, we found that the effect of CCl₄ in conditions of prolonged dark deprivation causes more significant structural and functional changes in hepatocytes, as well as leading to significant changes in the circadian rhythms of a number of parameters, which was not observed in the action of CCl₄ as a monofactor. We assume that the severity of structural and functional changes is due to the light-induced deficiency of melatonin, which has hepatoprotective properties. Thus, the mechanisms of CCl₄ action on CRs under conditions of light regime violations leave a large number of questions requiring further study, including the role of melatonin in these processes. Full article

This study was aimed to investigate the hepatoprotective potential of dapagliflozin and silymarin alone and in combination to combat carbon tetrachloride (CCl₄)-induced hepatotoxicity and the anticipated mechanisms. Thirty female Wistar rats were randomly allocated into five different groups. All the experimental animals except the normal control (Group I) were administered CCl₄. Additionally, Groups II, III, IV, and V were treated with gum acacia, silymarin, dapagliflozin, and a combination of dapagliflozin and silymarin, respectively, for 14 days. Dapagliflozin, silymarin alone, and in combination, significantly reduced (p < 0.05) serum levels of ALT, AST, AST:ALT ratio, and total bilirubin compared to CCl₄-intoxicated control rats. There was a notable reduction (p < 0.05) observed in the levels of IL-1beta, IL-6, TNF-alpha, nitrites, and 4-hydroxynonenal, accompanied by an elevation in catalase, superoxide dismutase, glutathione peroxidase, nuclear erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver homogenates of the groups treated with dapagliflozin, silymarin alone, and in combination, as compared to the CCl₄-intoxicated control group. Dapagliflozin in combination with silymarin showed a synergistic hepatoprotective effect. Our study reveals the profound hepatoprotective potential of dapagliflozin alone and in combination with silymarin in CCl₄-intoxicated Wistar rats by modulating the Nrf2 and HO-1 signaling pathways. Full article

An evaluation of the possible hepatotoxicity/hepatoprotective effects of a defatted extract of the above ground parts of Phlomis russeliana was conducted in vitro and in vivo. The extract was tested in vitro on hepatocytes alone and in a carbon tetrachloride (CCl₄)-bioactivation model. The same toxic substance was used for the in vivo evaluation on old Wistar rats. The extract was standardised via high performance liquid chromatography (HPLC) by the quantification of total flavonoids and verbascoside. Gallic acid equivalents were used to express the content of total phenolic compounds. The identification of flavonoids in this species was undertaken for the first time. The extract was not statistically hepatotoxic in vitro on the isolated rat hepatocytes. In the CCl₄-induced hepatotoxicity model, the extract had a hepatoprotective effect, which was concentration-dependant (the highest at 50 µg/mL). An in vivo study on old rats confirmed the observed antioxidant and hepatoprotective effects. The histological findings were favourable for the rats, given the extract and CCl₄ in combination. They had an unchanged organ structure, which is commensurable with these animals, treated with a combination of CCl₄ and silymarin. Full article

Forsythiaside A (FA) is an active constituent isolated from Forsythia suspensa, a beneficial herb used in traditional medicine known for its antioxidant and anti-inflammatory properties. Although various studies have suggested that FA has the protective effects, its impacts on arachidonic acid (AA) plus iron in vitro models and carbon tetrachloride (CCl₄)-induced mouse liver damage in vivo have not been explored. In this study, HepG2 cells were subjected to AA + iron treatment to induce apoptosis and mitochondrial impairment and determine the molecular mechanisms. FA exhibited protective effects by inhibiting cell damage and reactive oxygen species (ROS) production induced by AA + iron, as assessed via immunoblot and flow cytometry analyses. Further molecular investigations revealed that FA resulted in the activation of extracellular-signal-related protein kinase (ERK), which subsequently triggered the activation of AMP-activated protein kinase (AMPK), a critical regulator of cellular oxidative stress. Additionally, FA modulated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is a significant antioxidant transcription factor regulated by the AMPK pathway. For in vivo studies, mice were orally administered FA and then subjected to induction of CCl₄-based hepatotoxicity. The protective effect of FA was confirmed via blood biochemistry and immunohistochemical analyses. In conclusion, our findings demonstrated the protective effects of FA against oxidative stress both in vitro and in vivo, thus indicating that FA is a potential candidate for liver protection. Our study sheds light on the mechanistic pathways involved in the antioxidant effects of FA, highlighting the hepatoprotective potential of naturally occurring compounds in traditional herbs, such as FA. Full article

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. Full article

Abuse with hepatotoxic agents is a major cause of acute liver failure. The search for new criteria indicating the acute or chronic pathological processes is still a challenging issue that requires the selection of effective tools and research models. Multiphoton microscopy with second harmonic generation (SHG) and fluorescence lifetime imaging microscopy (FLIM) are modern label-free methods of optical biomedical imaging for assessing the metabolic state of hepatocytes, therefore reflecting the functional state of the liver tissue. The aim of this work was to identify characteristic changes in the metabolic state of hepatocytes in precision-cut liver slices (PCLSs) under toxic damage by some of the most common toxins: ethanol, carbon tetrachloride (CCl4) and acetaminophen (APAP), commonly known as paracetamol. We have determined characteristic optical criteria for toxic liver damage, and these turn out to be specific for each toxic agent, reflecting the underlying pathological mechanisms of toxicity. The results obtained are consistent with standard methods of molecular and morphological analysis. Thus, our approach, based on optical biomedical imaging, is effective for intravital monitoring of the state of liver tissue in the case of toxic damage or even in cases of acute liver injury. Full article

The continuous death of hepatocytes induced by various etiologies leads to an aberrant tissue healing process and promotes the progression of liver fibrosis and ultimately chronic liver diseases. To date, effective treatments to delay this harmful process remain an unmet clinical need. Cycloastragenol is an active phytochemical substance isolated from Astragalus membranaceus, a plant used in traditional Chinese medicine to protect the liver. Therefore, our study aimed to elucidate the efficacy of cycloastragenol on carbon-tetrachloride (CCl₄)-induced liver fibrosis in mice. We found that cycloastragenol at 200 mg/kg dosage exhibited anti-fibrotic efficacy as demonstrated by a decrease in collagen deposition, downregulation of mRNA expression of collagen type 1, and a reduction in the content of total collagens. In addition, cycloastragenol further augmented the levels of anti-fibrotic matrix metalloproteinases (Mmps), that is, Mmp8, proMmp9, and Mmp12, which play a pivotal role in fibrosis resolution. According to histological analysis and serum markers of hepatotoxicity, cycloastragenol protected the livers from damage and mitigated the increment of serum alanine aminotransferase and bilirubin implicating hepatoprotective efficacy against CCl₄. Moreover, cycloastragenol upregulated the mRNA expression of interleukin 6, a pleiotropic cytokine plays a vital role in the promotion of hepatocyte regeneration. In conclusion, cycloastragenol alleviated the progression of liver fibrosis in CCl₄-treated mice and its anti-fibrotic efficacy was mainly due to the hepatoprotective efficacy. Full article

This study evaluates the hepatoprotective activity of a Tamarix articulata extract against carbon tetrachloride-mediated hepatotoxicity in Wistar rats. Our results demonstrated that the oral administration of Tamarix articulata extract (50 mg/kg b.w.) significantly restored the serum levels of liver enzymes and antioxidant parameters (superoxide dismutase, catalase, glutathione reductase, and thiobarbituric reactive substances). Histopathology analysis revealed that Tamarix articulata extract significantly reduced hepatic fibrosis by inhibiting the necrosis of hepatocytes. Furthermore, serum pro-inflammatory (tumor necrosis factor-alpha, tumor growth factor-beta, and interleukin-6) markers were significantly restored. However, the anti-inflammatory cytokine adiponectin levels increased to normal levels in the group treated with Tamarix articulata extract. Additionally, we observed diminished reactive oxygen species production and the depolarization of mitochondrial membrane potential in hepatocytes extracted from animal livers treated with Tamarix articulata extract. Our findings suggest that Tamarix articulata extract prevents liver fibrosis induced by carbon tetrachloride and decreases the necrotic population of hepatocytes. These events restored the antioxidant enzymatic activity, serum levels of liver enzymes, and pro-inflammatory markers to their normal levels. Full article

This study investigated the druggability, pharmacokinetics and ethyl acetate extract of Teucrium polium (EA T. polium), from Ha'il, and the protective effect against carbon tetrachloride (CCl₄) induced liver cirrhosis in rats. The total antioxidant capacity (TAC) and scavenging activity of the extract were examined. The in vivo protective study was based on the use of an animal model of CCl₄-induced liver cirrhosis. Four groups of rats have been used: Group I: control rats; Group II: received CCl₄ in olive oil (0.5 mL/kg); Group III: received the EA T. polium (25 mg/kg) of pretreatment for seven days by gavage then CCl₄ in olive oil by gavage for 15 days. Group IV: received the EA of T. polium for seven days (25 mg/kg). EA T. polium was found to possess significant antioxidant capacity. CCl₄ caused a hepatotoxicity associated increase in both levels of AST and ALT, which were reduced back to normal values following EA T. polium pretreatment. Hepatotoxicity associated structural modifications of liver tissues and increase in thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD) and carbonyl proteins (CP), associated decreases in several assessed antioxidant enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT). The in vivo findings on the protective effect of T. polium were supported by its druggability, its pharmacokinetic properties and molecular docking assays. These results confirm the modulatory antioxidant and hepatoprotective potential of T. polium in this experimental liver cirrhosis model. T. polium phytochemicals are good candidates for further pharmaceutical explorations and drug design. Full article

Local tribes use the leaves of Ficus lepicarpa B. (Moraceae), a traditional Malaysian medicine, as a vegetable dish, a tonic, and to treat ailments including fever, jaundice and ringworm. The purpose of this study was to look into the possible therapeutic effects of F. lepicarpa leaf extract against carbon tetrachloride (CCl₄)-induced liver damage in rats. The DPPH test was used to measure the antioxidant activity of plants. Gas chromatography-mass spectrometry was used for the phytochemical analysis (GCMS). Six groups of male Sprague-Dawley rats were subjected to the following treatment regimens: control group, CCl₄ alone, F. lepicarpa 400 mg/kg alone, CCl₄ + F. lepicarpa 100 mg/kg, CCl₄ + F. lepicarpa 200 mg/kg and CCl₄ + F. lepicarpa 400 mg/kg. The rats were euthanized after two weeks, and biomarkers of liver function and antioxidant enzyme status were assessed. To assess the extent of liver damage and fibrosis, histopathological and immunohistochemical examinations of liver tissue were undertaken. The total phenolic content and the total flavonoid content in methanol extract of F. lepicarpa leaves were 58.86 ± 0.04 mg GAE/g and 44.31 ± 0.10 mg CAE/g, respectively. F. lepicarpa’s inhibitory concentration (IC₅₀) for free radical scavenging activity was reported to be 3.73 mg/mL. In a dose-related manner, F. lepicarpa was effective in preventing an increase in serum ALT, serum AST and liver MDA. Histopathological alterations revealed that F. lepicarpa protects against the oxidative stress caused by CCl₄. The immunohistochemistry results showed that proinflammatory cytokines (tumour necrosis factor-α, interleukin-6, prostaglandin E₂) were suppressed. The antioxidative, anti-inflammatory, and free-radical scavenging activities of F. lepicarpa can be related to its hepatoprotective benefits. Full article

The protective effects of chlorogenic acid (CGA) against liver injury were evaluated by its reduction in carbon tetrachloride (CCl₄)-induced hepatic damage in ICR mice. The animals were orally given CGA (60, 100, and 200 mg/kg, respectively) or silymairn (200 mg/kg) daily with 0.3% CCl₄ administration (3 mL/kg, dissolved in olive oil) after medicament treatment on the 7th day. Compared with the normal group, CCl₄ caused severe impairment in liver according to the evidence of significant reduction in the level of total albumin and expansion (p < 0.05) of the activities in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), cholesterol, triglyceride (TG), and total albumin in serum, decreased the level of glutathione (GSH), and diminished the activities of catalase, superoxide dismutase (SOD), glutathione reductase (GSH-Rd), and glutathione peroxidase (GSH-Px) in liver while increasing the level of hepatic thiobarbituric acid-reactive substances (TBARS). However, oral administration of CGA or silymarin could significantly (p < 0.05) decrease the serum levels of AST, ALT, cholesterol, TG, and total albumin and elevated the serum total albumin and the activities of GSH, catalase, SOD, GSH-Rd, and GSH-Px while leading to decline the TBARS in liver compared with CCl₄-intoxicated group. Moreover, histopathology displayed that CGA decreased the formation of lesions in liver resulted from CCl₄. The outcomes indicate that CGA shows the efficiency hepatoprotective consequences for CCl₄-incited liver injuries in mice by the elevation of the activities of antioxidant enzymes and hindrance of lipid peroxidation. Full article

The aim of this study was to evaluate the effect of Vernonia amygdalina leaf extract (VALE) on the carbon tetrachloride-induced hepatotoxicity (CCl₄) in broiler chickens. A total of 360-day-old broilers were divided into 4 treatments of 90 birds each consisting of 6 replicates of 15 birds each. The treatments were birds offered 1 mL/kg BW saline (control group), 100 mg/kg BW VALE, 1 mL/kg BW CCl₄ (CCl₄-treated group), and 100 mg/kg BW VALE + 1 mL/kg BW CCl₄ (VALE + CCl₄ group). Blood samples were collected at 42 days of age and analyzed for the liver enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and selected biochemical parameters. The experiment was laid out in a completely randomized design. The results obtained showed that VALE had the potential to mitigate the adverse effects of CCl₄ on protein and lipid metabolism as reflected in the low serum malondialdehyde (MDA) levels, which is a marker of lipid peroxidation. The aqueous extract of Vernonia amygdalina (VA) at a dose of 100 mg/kg body weight showed a moderate hepatoprotective effect by reducing serum AST levels (p < 0.05). The levels of serum AST, ALP, ALT, and GGT were significantly increased in CCl₄-treated birds compared to the control group, reflecting carbon tetrachloride-induced liver damage. The VALE + CCl₄ group showed a significantly higher amount of ALP compared to birds treated with carbon tetrachloride, suggesting a hepatoprotective effect. To conclude, Vernonia amygdalina aqueous extract can be used to confer protection against hepatotoxicity, which can induce severe hepatocellular damage in birds. Full article