Carbon Tetrachloride-induced Hepatotoxicity Research Articles

Effects of Ethyl Acetate Fraction of Mangifera haden Seeds on Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats

The present study investigated the effects of ethyl acetate fraction of Mangifera haden seeds on carbon tetrachloride-induced liver damage in wistar albino rats. The phytochemical compositions and acute toxicity studies of crude extract and Mangifera haden seed fraction were determined using standard methods. Albino rats (60) randomly grouped into twelve of five rats each were used for this study. Determination of total bilirubin and protein, lipid peroxidation, liver enzymes marker, antioxidant enzymes, glutathione, lipid profile analysis and histological examination were carried out using standard methods. Phytochemical constituents of crude extract and ethyl acetate fraction of Mangifera haden seed showed that they contain relative amount of flavonoids, phenolics, saponins, tannins, terpenoids, triterpenes, alkaloids and coumarins. Liver injury was induced with carbon tetrachloride (CCl4) at a dose of 1.0 ml/kg body weight of the animals. All the CCl4 intoxicated rats displayed hyperlipidemia as shown by their elevated levels of serum total cholesterol (TC), triacylglycerol (TAG), low density lipoprotein (LDL), and reduction in high density lipoprotein (HDL) levels. The administration of ethyl acetate fraction of Mangifera haden seeds significantly (P = 0.05) lowered the levels of serum TC, TAG, LDL, and increased HDL levels. The level of serum malondialdehyde (MDA) significantly (P = 0.05) increased in the CCl4 group as compared to the normal and treated groups. The elevated level of serum MDA decreased (P = 0.05) significantly at the treatment of rats with 200, 400 and 600 mg/kg of ethyl acetate fraction. The rats treated with CCl4 produced significant (P = 0.05) increase in serum ALT, AST and ALP when compared to the normal group. Animals treated with varying doses of ethyl acetate fraction produced significant (P = 0.05) reduction of serum ALT, AST and ALP activities when compared to the CCl4-untreated group. The activities of hepatic antioxidant enzymes (SOD, CAT and GPx) and glutathione concentration significantly (P = 0.05) decreased in CCl4­-untreated group compared to the normal group. The decreased activities of the antioxidant enzymes and glutathione concentration in CCl4 intoxicated rats were ameliorated/modulated more effectively in rats treated with 200, 400 and 600 mg/kg ethyl acetate fraction of Mangifera haden seed. Total bilirubin (TB) concentrations significantly (P = 0.05) increased in CCl4-untreated group when compared to the normal group. Oral treatment of rats with varying doses (200, 400, 600 mg/kg) of ethyl acetate fraction caused a significant (P = 0.05) decrease in the serum TB levels. Administration of CCl4 showed a reduction in serum total proteins. Treatment of the animals with 200, 400 and 600 mg/kg of ethyl acetate fraction caused significant (P = 0.05) increase in serum total potein. Histological examination showed hepatoprotective properties of plant’s fractions. The compounds found in the different fractions (ethyl acetate and n-hexane) of Mangifera haden seeds are 9-Octadecenoic acid (Z)-, methyl ester, (Z) –Oleic acid and so on. Therefore the medicinal importance of the plant is been established.

Dietary Importance of Lycopene Against Carbon Tetrachloride Induced Hepatotoxicity in Rats

Dietary Importance of Lycopene Against Carbon Tetrachloride Induced Hepatotoxicity in Rats

Protective effect of Helianthus annuus seeds extract against CCl4-induced hepatocellular damage

Carbon tetrachloride (CCl4) is a hepatotoxin that causes toxicity in animals on its exposure. Hepatotoxins lead to hepatic demage that is treated by generating antioxidant effect. Synthetic and as well as natural drugs are available for this purpose but phyto-based herbal medicines got paramount importance against drug induced hepatotoxicity Current research was conducted to inspect the protective effect of aqueous extract of Helianthus annuus seeds pre-treatment on the carbon tetrachloride-induced hepatotoxicity in Balb C mice. Study covered the valuation of the enzymatic activity such as alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), alkaline phosphatase (ALP) and Lactate dehydrogenase (LDH) and other biochemical components like bilirubin, total protein, catalase, glutathione (GSH), malondialdehyde bis-(dimethyl acetal) tetra ammonium (MDA). The induction of carbon tetrachloride (CCl4) caused rise in plasma ALAT, ASAT, ALP and LDH. Helianthus annuus seeds extract (HA extract) pre-treatment obliterated CCl4-induced deviations in the activities of these enzymes significantly. Bilirubin level increased whereas total protein contents decreased after the induction of CCl4 this effect was reversed by HA extract. Induction of CCl4 caused increased in MDA level while decrease in GSH and catalase. Helianthus annuus seeds extract also abolished these changes. Helianthus annuus seeds extract pre-treatment also prevented CCl4-induced changes in bilirubin and total protein contents. Carbon tetrachloride treatment resulted in huge hepatic damage. This was prevented by Helianthus annuus seeds extract. These results show that Helianthus annuus seeds extract pre-treatment prevented the mice from CCl4-induced hepatic damage, which visibly shows its defensive effects against hepatic damage.

Evaluation of the ameliorative role of ginger (Zingiber officinale) extract against carbon tetrachloride-induced hepatotoxicity in male albino rats

Evaluation of the ameliorative role of ginger (Zingiber officinale) extract against carbon tetrachloride-induced hepatotoxicity in male albino rats

Investigating the Anti-inflammatory Effects of Rutin in Carbon Tetrachloride-induced Hepatotoxicity: Role of TLR4/MyD88/NFκB Signaling Pathway Modulation

Objectives Rutin protects and stabilizes hepatocytes and is used to treat hepatitis, liver cirrhosis, and other diseases. However, there is little evidence to suggest that Rutin is associated with CCl4-induced hepatotoxicity. In this study, we investigated the effects of Rutin on CCl4-induced liver inflammation and discussed in vivo and in vitro mechanisms. Materials and Methods CCl4 was used to induce liver inflammation, and Rutin was used for intervention in mice. Then the body weight, liver weight, and liver inflammation of all mice were measured. Western blotting and RT-PCR were used to assess TLR4/MyD88/NFκB inflammation signaling pathways and inflammatory gene expression. Finally, TLR4 was activated in primary hepatocytes to verify the above signal pathways. Findings CCl4 mice developed liver function damage and liver inflammation. Further investigations showed that the inhibitory effects of Si on inflammation were mediated by TLR4/MyD88/NFκB inflammation signaling pathways inhibition. Primary hepatocyte studies also confirmed the participation of these signaling pathways and proteins. Significance Rutin improved CCl4-induced liver inflammation. Such mechanisms may be related to TLR4/MyD88/NFκB inflammation signaling pathways.

Deciphering Molecular Mechanisms of Carbon TetrachlorideInduced Hepatotoxicity (Fibrosis): A Brief Systematic Review.

The liver plays a critical role in metabolic processes, making it vulnerable to injury. Researchers often study carbon tetrachloride (CCl4)-induced hepatotoxicity in model organisms because it closely resembles human liver damage. This toxicity occurs due to the activation of various cytochromes, including CYP2E1, CYP2B1, CYP2B2, and possibly CYP3A, which produce the trichloromethyl radical (CCl3*). CCl3* can attach to biological molecules such as lipids, proteins, and nucleic acids, impairing lipid metabolism and leading to fatty degeneration. It can also combine with DNA to initiate hepatic carcinogenesis. When exposed to oxygen, CCl3* generates more reactive CCl3OO*, which leads to lipid peroxidation and membrane damage. At the molecular level, CCl4 induces the release of several inflammatory cytokines, including TNF-α and NO, which can either help or harm hepatotoxicity through cellular apoptosis. TGF-β contributes to fibrogenesis, while IL-6 and IL-10 aid in recovery by minimizing anti-apoptotic activity and directing cells toward regeneration. To prevent liver damage, different interventions can be employed, such as antioxidants, mitogenic agents, and the maintenance of calcium sequestration. Drugs that prevent CCl4- induced cytotoxicity and proliferation or enhance CYP450 activity may offer a protective response against hepatic carcinoma.

Hepatoprotective and in vivo antioxidant effects of granulometric classes and decoction of Ficus dicranostyla Mildbread leaves powders against carbon tetrachloride-induced hepatotoxicity in Wistar rats.

Ficus dicranostyla is a plant from the Moraceae family commonly used in African countries for its nutritional value and its believed medicinal properties. Its antioxidant in vitro capacity and its richness in phenolic compounds have been previously demonstrated. This work aimed at evaluating the hepatoprotective and in vivo antioxidant activities of different granulometric fractions of the F. dicranostyla leaves against carbon tetrachloride-induced hepatotoxicity in rats. Powdery fractions (<125, 250-125, and ≥250 μm), and the unsieved powder, obtained from the F. dicranostyla leaves were water-dissolved and given orally to rats at the same dose (250 mg/kg body weight) before administering carbon tetrachloride intraperitoneally (1 mL/Kg bw). The lipid status parameters (total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol), hepatic toxicity through aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in blood plasma, and antioxidant status by measuring the malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) in liver homogenate were performed. The activities of all parameters registered a significant (p < .05) alteration in CCl4-treated rats, which were significantly recovered toward an almost normal level in coadministered with Ficus dicranostyla leaf powder samples in a particle size-dependent manner. Results suggest that the smaller particle size of the powder fraction, as well as the decoction powder of Ficus dicranostyla, may be used as hepatoprotective and antioxidant agents.

Phytochemical and Hepatoprotective Activity of Prosopis juliflora Barks on Different Models

Liver injury is a common disorder where natural remedies are practiced from ancient time from plant source which shows alternative treatment in a safe manner. The Hepatoprotective activity of methanolic extract of Prosopis juiliflora bark part was taken for evaluation in screening. The model chosen for the study is carbon tetrachloride (0.1ml/kg) and the standard drug silymarin of 20mg/kg was used for the study for 21 days. The hepatoprotective effect of the methanolic extract against the carbon tetrachloride-induced hepatotoxicity in wistar rats has been demonstrated by the substantial and severe reduction of enzymes in the serum.

To study the Hepatoprotective Activity of the Fruit of Exogenous Plant of Xanthophyceae family Against Carbon Tetrachloride Induced Hepatotoxicity in Albino Rats.

The Hepatic is midst the best industrious and pennon organs in the feasible body. Hepatotoxicity is a symbol intermediary of morbidity and lenity, and its extent is leave off increment appointment by steady old-fashioned in the industrialized nations. Hepatotoxicity is characterized by atomic pyknosis and eosinophilic cytoplasm, followed by copious rash hepatic poison, pudginess changes, lipid peroxidation leads to hepatic centrilobular necrosis. Paracetamol, reluctant tubercular drugs, demon rum, and azathioprine are meditate on to be the tricky venture factors implicated in the progression of hepatotoxicity. Unusual signaling mechanisms, such as activation of transmissible represent encode alike Kupffer cells, simple hew to pieces cells, incendiary mediators, intracellular Ca2 concentration and reactive oxygen species are involved in the pathogenesis of hepatotoxicity. At realistic, helter-skelter is petite aglow panacea is at hand to squeamish patients give hepatotoxicity becoming to deficiency of colleague of signaling culprits involved in the pathogenesis of hepatotoxicity. Gross models are zoological seasoned to reform esteem the plague pathogenesis and develop drugs for hepatotoxicity. In the physical study, we take on submit discrete extremist models for hepatotoxicity, which may frankly vistas for developing new drugs to treat hepatotoxicity.

Profile of 5-HT2A receptor involved in signaling cascades associated to intracellular inflammation and apoptosis in hepatocytes and its role in carbon tetrachloride-induced hepatotoxicity

Previously, we found that the 5-HT2A receptor plays a key role in cell injury. However, the mechanism by which the 5-HT2A receptor mediates intracellular processes remains unclear. In this study, we aimed to clarify this intracellular process in hepatocyte LO2 cells and evaluate its role in CCl4-induced hepatotoxicity in mice. In vitro, both the agonist and overexpression of 5-HT2A receptor could promote 5-HT degradation by upregulating the expression of 5-HT synthases and monoamine oxidase-A (MAO-A) to cause overproduction of ROS in mitochondria. We refer to this as the activation of the 5-HT degradation system (5DS) axis, which leads to the phosphorylation of JNK, p38 MAPK, STAT3, and NF-κB; upregulation of Bax, cleaved-caspase3, and cleaved-caspase9; and downregulation of Bcl-2, followed by apoptosis and oversecretion of TNF-α and IL-1β in cells. This phenomenon could be markedly blocked by the 5-HT2A receptor antagonist, MAO-A inhibitor, or gene-silencing MAO-A. Through protein kinases C epsilon (PKCε) agonist treatment and gene silencing of the PKCε and 5-HT2A receptor, we demonstrated that the 5-HT2A receptor controls 5-HT synthases and MAO-A expression via the PKCε pathway in cells. Unexpectedly, we discovered that PKCε-mediated phosphorylation of the AKT/mTOR pathway is also a consequence of the activation of the 5DS axis. Furthermore, we confirmed that the inhibition of the 5DS axis using the 5-HT2A receptor antagonist could prevent hepatotoxicity induced by CCl4 both in vitro and in vivo, inhibiting the aforementioned signaling cascades, inflammation, and apoptosis, and that the 5DS activation area overlapped the necrotic area of mouse liver. Taken together, we revealed a 5DS axis in hepatocytes that controls the signaling cascades associated with inflammation and apoptosis and confirmed its role in CCl4-induced hepatotoxicity.

Vernonia amygdalina leaf extract protects against carbon tetrachloride-induced hepatotoxicity and nephrotoxicity: a possible potential in the management of liver and kidney diseases

The rising prevalence of liver and kidney diseases is worrisome and constitutes a major threat to public health. The present study investigates the medicinal potentials of Vernonia amygdalina leaves in the management of liver and kidney diseases. Albino rats were randomly divided into five groups each containing 5 animals. In all groups, except group I (control), animals were exposed to 3 ml/kg bw of CCl4 and then administered further different treatments. Groups III, IV, and V each were treated with 50 mg/kg bw, 100 mg/kg bw of bitter leaf extract, and 100 mg/kg bw of silymarin, respectively. Group II animals were left untreated after exposure to toxicant. Activities of creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), as well as the level of urea, uric acid, and bilirubin were determined in the serum and tissue homogenates. Lipid profile as well as activities of superoxide dismutase (SOD) and catalase (CAT) were also determined. Exposure to CCl4 resulted in a significant increase in CK, AST, ALP, and ALT levels as well as bilirubin, urea, and uric acid when compared to the control. Lipid profile was disrupted, activities of SOD and CAT were markedly inhibited and the level of GSH was significantly depleted. However, treatment with V. amygdalina reversed the toxic trend in a dose-dependent manner comparable to animals treated with silymarin. In conclusion, V. amygdalina leaf extract restored deranged lipid profile, distorted histoarchitecture as well as liver and kidney function markers. Hence, the plant is a potential candidate for the management of liver and kidney diseases.

Hepatoprotective Activity of Merremia tridentata against Carbon Tetrachloride Induced Hepatotoxicity in Rats

Objectives: Liver performs a variety of function including storage and purification of blood, secretion of bile, synthesis of plasma proteins and drug detoxification. In an attempt to study the biochemical and connective tissue metabolism during the progression of hepatic fibrosis and to gain more insight into the mechanisms leading to the altered metabolic processes in human hepatic fibrosis, an experimental animal model was developed using administration of carbon tetrachloride (CCl4). Methods: The present study evaluates the hepatoprotective activity of Merremia tridentate plant extract against CCl4 induced liver damage in Wistar albino rats. CCl4 caused a rise in liver and serum AST, ALT, ALP, ACP and total Bilirubin content. Pretreatment and post treatment of rats with ethanolic and aqueous extracts (50,100 & 200 mg/kg b.wt) significantly reduced these serum parameters and antioxidant enzymes levels compared to CCl4 induced rats. The post-treatment had better activity than the pre-treatment groups. Findings: Preliminary phytochemical analysis showed the presence of tannins, saponins, flavonoid, alkaloid, anthocyanin, quinones, glycosides, cardiac glycosides, terpinoids, phenol, coumarin and reducing sugar which may be responsible for the hepatoprotective activity. The liver stabilization activity is due to the presence of bioactive compounds in the Merremia tridentate extracts. Conclusions: Thus, Merremia tridenta extracts ameliorated the liver damage caused by the CCl4and raised the liver and serum enzymes to normal levels: Keywords: Liver; Detoxification; Carbon Tetrachloride; Merremia trident; Hepatotoxins

Prophylactic and curative effects of Carica papaya Linn. pulp extract against carbon tetrachloride-induced hepatotoxicity in male rats

Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances’ metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl4-induced rat hepatotoxicity. Five groups of rats were created, control, PE, CCl4, (PE-CCl4): The rats were administered with PE pre and during CCl4 injection, and (PE-CCl4-PE): The rats were administered with PE pre, during, and after CCl4. The markers of oxidative stress (“OS”: oxidant and antioxidants), inflammation [nuclear factor-κB, tumor necrosis factor-α, and interleukin-6], fibrosis [transforming growth factor-β], and apoptosis [tumor suppressor gene (p53)] were evaluated. Additionally, liver functions, liver histology, and kidney functions were measured. Also, PE characterization was studied. The results showed that PE, in vitro, has a high antioxidant capacity because of the existence of phenolics, flavonoids, tannins, terpenoids, and minerals. Otherwise, the PE administration [groups (PE-CCl4) and (PE-CCl4-PE)] exhibited its prophylactic and therapeutic role versus the hepatotoxicity induced by CCl4 where PE treatment improved liver functions, liver histopathology, and renal functions by decreasing oxidative stress, inflammation, fibrosis, and apoptosis induced by CCl4. Our study elucidated that PE contains high amounts of phenolics, flavonoids, tannins, terpenoids, and ascorbic acid. So, PE exerted significant prophylactic and curative effects against hepatotoxicity induced by CCl4. These were done by enhancing the markers of antioxidants and drug-metabolizing enzymes with reductions in lipid peroxidation, inflammation, fibrosis, and apoptosis. PE administration for healthful rats for 12 weeks had no negative impacts. Consequently, PE is a promising agent for the prohibition and therapy of the toxicity caused by xenobiotics.

Comparative efficacy of ternary Cu (II) complex and Zn (II)-complex in amelioration of carbon tetrachloride-induced hepatotoxicity in vivo

Cu (II) and Zn (II) are two of the most favored metals in synthesis chemistry, encompassing their therapeutic potentials. The present study aims to evaluate the comparative ameliorative potential of a group B carcinogen, CCl4-induced hepatotoxicity, by our recently synthesized and characterized ternary Cu and Zn-based complexes in vivo. Three groups of rats were treated with CCl4 alone and with the combination of Cu (II) complex and Zn (II) complex beside the control negative group without any treatment. After completion of the treatment, the samples were subjected to biochemical and histological analysis. The analysis demonstrated extensive alteration in redox status, liver markers, and hepatotoxicity markers in the CCl4, treated group compared to the control group. However, the Cu (II) complex showed significant improvement in most of the parameters under the study. Also, histopathological evaluation and comet assay further consolidated the findings. Hence, this investigation reveals that Cu (II) complex has more substantial ameliorative potential in ceasing CCl4-induced hepatotoxic insults. Therefore, the ternary Cu (II) complex act as a more potent chemotherapeutic agent in cancer treatment with milder side effects than the Zn (II) complex.

Effects of Hydroalcoholic Extract of Lepidium Sativum L. on Carbon Tetrachloride-Induced Hepatotoxicity in Mice

Background: Carbon tetrachloride (CCl4 ) as an organic solvent causes symptoms of acute and chronic liver injury, including necrosis, fat changes, liver cancer, and cirrhosis. Lepidium sativum contains flavonoids, alkaloids, and antioxidant components.&#x0D; Objectives: This study aims to investigate the hepatic protection of L. Sativum Extract (LSE) on CCl4 -induced hepatotoxicity in mice. &#x0D; Methods: A total of 25 male mice were randomly divided into five groups (n=5): control (olive oil), CCl4 , and 3 LSE groups. Except for the control group, all the mice received CCl4 (50%, 0.5 mL/kg) intraperitoneally twice a week for 4 weeks. The mice in the LSE groups were treated daily with LSE (200, 400, and 600 mg/kg) via IP injection. The animals were sacrificed 24 h after the last dose, and liver function parameters, such as Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), and Glutathione (GSH) were determined. Furthermore, 0.1 g of liver tissue was removed for histochemical analysis.&#x0D; Results: Significant differences were observed in GSH, ALP, AST, and ALT levels between the CCI4 and the control groups. Compared to the CCl4 group, LSE treatment significantly decreased plasma ALT (P&lt;0.05), AST in all doses (P&lt;0.001), and ALP in 600 mg/kg (P&lt;0.001). In addition, LSE treatment significantly increased GSH in 400 mg/kg (P&lt;0.01) and 600 mg/kg (P&lt;0.001).&#x0D; Conclusion: LSE has hepatic protective activity against CCl4 -induced injuries. The possible anti-hepatotoxic mechanisms may be related to the presence of flavonoids, triterpenes, alkaloids, tannin, and coumarins in the LSE by inhibiting the free radicals mediated damage.&#x0D;

ANTIULCER, ANALGESIC AND HEPATOPROTECTIVE ACTIVITIES OF HYDROALCOHOLIC ROOT EXTRACT OF JURINEA DOLOMIAEA BOISS

The herb Jurinea Dolomiaea Boiss, which is a member of the Astraceae family, has long been used in Ayurveda to treat liver diseases and as an anticancer, antioxidant, and anti-diabetic. The antiulcer, analgesic, and hepatoprotective effects of Jurinea dolomiaea Boiss aqueous and hydroalcoholic root extracts against carbon tetrachloride-induced hepatotoxicity in albino wistar rats were investigated in this work. The experimental rats were given Jurinea dolomiaea root hydroalcoholic extract (100 mg/kg and 200 mg/kg p.o.) daily for seven days. By measuring SGOT, SGPT, ALP, and total bilirubin, the hydroalcoholic extract of Jurinea dolomiaea roots was examined for its hepatoprotective properties. The toxic effect of carbon tetrachloride was greatly reduced in the rats treated with the hydroalcoholic extract of Jurinea dolomiaea roots by restoring the elevated levels of SGOT, SGPT, ALP, and total bilirubin compared to the toxicant control. Jurinea dolomiaea root hydroalcoholic extract shown notable hepatoprotective effects.

Ameliorating Potential of Marketed Formulations Containing Prebiotics And Probiotics Against Carbon Tetrachloride-Induced Hepatotoxicity in rats

In the present work, two marketed formulations VELGUT® (combination of prebiotic and probiotics) and VIZYLAC® (probiotic only) were assessed for a protective effect against carbon tetrachloride-induced chronic liver injury model in rats. Rats were randomly divided into four groups. Normal Control (treated with normal saline) and CCl4 treated group (treated with 1 ml/kg intraperitoneal injection of CCl4 once daily for 10 days followed by twice a week up to 49 days). Test groups composed of the oral treatment of VELGUT (1 mg kg-1) along with CCl4 (T1) and oral treatment of VIZYLAC (4 mg kg-1) along with CCl4. CCl4 treatment in the test group was similar to group 2. At the end of the treatment, various serum biochemical parameters like Alanine aminotransferase (ALT), Aspartate Aminotransferase, (AST), Alkaline Phosphatase (ALP), direct bilirubin, total protein, and albumin levels were measured. Serum cholesterol, glucose and malondialdehyde (MDA) levels were also measured. A small piece of the liver was collected to perform histopathological studies. Serum AST, ALT, ALP, and direct bilirubin were found to be significantly lower as compared to CCl4 intoxicated rats. The level of total protein and albumin was improved. The level of MDA, glucose and cholesterol was improved as compared to CCl4 treated group.

Protective effect of Euphorbia thymifolia and Euphorbia hirta against carbon tetrachloride-induced hepatotoxicity in Wistar rats

Objectives The present study aims to investigate the protective effect of Euphorbia thymifolia and Euphorbia hirta extracts on in vitro antioxidant activity and in vivo analysis on hepatic marker enzyme levels and histopathological changes in the liver of carbon tetrachloride (CCl4) induced hepatotoxicity rats. Materials and methods This study includes 42 adult male Albino Wistar rats randomly divided into seven treatment groups, including control (basal diet, G1), CCl4-induced single dose (1.5 ml/kg, i.p.) as the negative control (G2), G1 supplemented with 300 mg/kg of ethanol extract of E. thymifolia (G3) and E. hirta (G4), G2 supplemented with 300 mg/kg of ethanol extract of E. thymifolia (G5), E. hirta (G6), and silymarin (25 mg/kg b.w.) used as a standard drug (G7) for 21-days experimental period. Results The ethanolic extracts of E. thymifolia and E. hirta exhibited potential in vitro antioxidant activity in a dose-dependent manner (25 μg/ml, 50 μg/ml, 100 μg/ml, 200 μg/ml and 250 μg/ml). Oxidative stress caused by CCl4-induced the liver damage, including changes in liver marker enzymes (aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase), enzymatic (superoxide dismutase and catalase), non-enzymatic antioxidants (lipid peroxides and glutathione) and hepatocellular alterations such as hydropic degeneration, irregular hepatocytes, and distention of the vein. Administration of E. thymifolia and E. hirta significantly (p < 0.05) restored the enzyme activity along with the histology of the liver. Conclusion The results from the current study demonstrate that E. thymifolia and E. hirta have the property of restoring hepatic redox capacity and antioxidant activities against CCl4-induced acute liver damage.

Ameliorative effect of montelukast against carbon tetrachloride-induced hepatotoxicity: Targeting NLRP3 inflammasome pathway

AimsMontelukast, a selective antagonist of type 1 cysteinyl-leukotriene receptors, has antioxidant and anti-inflammatory abilities. This study aimed to explore its hepatoprotective impact against CCl4-induced hepatotoxicity compared to a standard hepatoprotective agent, silymarin. Main methodsTwenty-four albino mice were used in this study, CCl4 (1 mL/kg of 1:1 v/v CCl4:olive oil) was singly injected in mice, and montelukast was administered in a dose of 10 mg/kg. Key findingsResults revealed that montelukast significantly improved CCl4-induced alterations in both structure and function of the liver, verified respectively through histopathology and by the reduced levels of ALT, AST, ALP, and GGT upon comparison with CCl4. Also, montelukast prevented the induction of oxidative stress via decreasing hepatic MDA content and enhancing GSH levels. Moreover, montelukast produced a profound decrease in the levels of hepatic NLRP3 and its adaptor protein, ASC, and a reduction in the pro-inflammatory markers, NF-κB, IL-1β, TNF-α, and IL-6. In addition, montelukast markedly reduced liver fibrosis, as illustrated by Masson Trichrome, and the decreased hepatic levels of TGF-β and α-SMA. Furthermore, montelukast efficiently decreased apoptosis as manifested by the decreased hepatic level of Caspase 3. SignificanceMontelukast protected against CCl4-induced hepatotoxicity via exerting antioxidant, anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.

Hepatoprotective Activity of Methanolic Extract of Leaves Parts of Chenopodium Album Linn on Carbon Tetrachloride Induced Hepatotoxicity in Waster Rats.

The liver is among the most complex and important organ in the human body. Its primary function is to control the flow and safety of substances absorbed from the digestive system before distribution of these substances to the systemic circulatory system. Carbon tetra chloride is well- known hepatotoxin which is widely used to induce hepatotoxicity in laboratory animals. Chenopodium album Linn also known as frost Bilte, Pigweed (Canada), found to have antipruritic and antinociceptic, sperm immoblizing agent, cryptomeridiol and 8- alpha-acetoxycryryptomeridiol as growth promoting activity, (patak and pandey) Chenopodium album has reported hepatoprotective activity, antifungal, antihelminitic, contraceptive, antipyretic and antinoceipetive activity. The present study was aimed to investigate hepatoprotective activity of alcoholic extract of leaves parts of Chenopodium album Linn on carbon tetrachloride induced hepatotoxicity in waster rats. The leaves of plant was dried under shed and then powdered. The Powder was packed into a Soxhlet apparatus, extract was concentrated in steam bath till the complete evaporation of the solvent. Administration of Carbon tetra chloride subcutanously (SC) in the lower abdomen, in a suspension of liq. paraffin (LP, 1:1 v\v) at the dose of 1ml\kg B.W. on alternate days of week showed significant increase in SGOT and SGPT. Methanol extract of Chenopodium album Linn. at dose of 200mg\kg B.W. P.O. (Group III) in a carbon tetra chloride treated groups cause significant decrease in SGOT and SGPT. Result of biochemical parameters of Chenopodium album Linn. (400 mg\kg B.W. P. O.), showed significantly arrestedin in rise of level of SGOT, SGPT was found in group IV. The standard drug Liv2R showed significant reduction in all parameters when compared to CCl4 treated groups. This study concluded that methanolic extract of Chenopodium album Linn. has hepatotprotective effect in CCl4 induced liver damage. This effect is evident especially with high dose of Chenopodium album Linn. (400 mg\kg B.W. p.o) because it caused drastic fall in serum markers as compared to other doses of Doses of Chenopodium Album Linn.&#x0D; Abbreviations- serum glutamate oxaloacetatae transaminase (SGOT) and serum Glutamate Pyruvate Transaminase (SGPT)&#x0D; Keywords- Chenopodium album Linn., methanolic extract, carbon tetrachloride (CCl4), hepatotoxicity