CCl4-intoxicated Rats Research Articles

Unlocking Synergistic Hepatoprotection: Dapagliflozin and Silymarin Combination Therapy Modulates Nuclear Erythroid 2-Related Factor 2/Heme Oxygenase-1 Pathway in Carbon Tetrachloride-Induced Hepatotoxicity in Wistar Rats.

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.

Hypoglycemic and hepatoprotective activity of Phellinus fastuosus on streptozotocin-induced diabetic rats and carbon tetrachloride-intoxicated rats, respectively

BackgroundPhellinus fastuosus is a wood-eating medicinal fungus from Western Ghats of India. Therefore, we investigated hypoglycemic and hepatoprotective effects of P. fastuosus aqueous extract on streptozotocin-induced diabetic and carbon tetrachloride (CCl4) induced hepatotoxicity in rats, respectively.ResultAs compared to the diabetic control group, a 400 mg/kg dose had significant hypoglycemic effects, including a reduction in blood glucose (24.44%) and gain in body weight. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity reduced by 31.81% and 32.84%, respectively, were also noted, along with decreases in triglycerides (24.32%) and cholesterol (25.89%) levels. The albumin, bilirubin and creatinine levels were also significantly reduced after administration of P. fastuosus extract in diabetic rats. Administration of P. fastuosus extract showed a substantial decrease in the activity of ALT, AST, alkaline phosphatase (ALP), catalase (CAT) and superoxide dismutase (SOD) in addition a decrease in the level of lipid peroxidation (LPO) as compared to CCl4-intoxicated rats. The cumulative effect of CCl4 increased the erythrocyte membrane peroxidation, whereas P. fastuosus extract reduced the cholesterol and increased phospholipid, thus preventing the alteration of membrane fluidity as compared to CCl4-intoxicated rats. FTIR and HR-LC-MS-based metabolic profiling revealed the presence of various functional groups and bioactive metabolites.ConclusionThe extract showed the hypoglycemic and hepatoprotective effects due to the presence of various bioactive metabolites. Exploration of therapeutic potential of P. fastuosus using bioassay-guided fractionation is needed.

Mechanistic insight into the hepatoprotective effect of Moringa oleifera Lam leaf extract and telmisartan against carbon tetrachloride-induced liver fibrosis: plausible roles of TGF-β1/SMAD3/SMAD7 and HDAC2/NF-κB/PPARγ pathways

The increasing prevalence and limited therapeutic options for liver fibrosis necessitates more medical attention. Our study aims to investigate the potential molecular targets by which Moringa oleifera Lam leaf extract (Mor) and/or telmisartan (Telm) alleviate carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Liver fibrosis was induced in male Sprague-Dawley rats by intraperitoneal injection of 50% CCl4 (1 ml/kg) every 72 hours, for 8 weeks. Intoxicated rats with CCl4 were simultaneously orally administrated Mor (400 mg/kg/day for 8 weeks) and/or Telm (10 mg/kg/day for 8 weeks). Treatment of CCl4-intoxicated rats with Mor/Telm significantly reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities compared to CCl4 intoxicated group (P < 0.001). Additionally, Mor/Telm treatment significantly reduced the level of hepatic inflammatory, profibrotic, and apoptotic markers including; nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α), transforming growth factor-βeta1 (TGF-β1), and caspase-3. Interestingly, co-treatment of CCl4-intoxicated rats with Mor/Telm downregulated m-RNA expression of histone deacetylase 2 (HDAC2) (71.8%), and reduced protein expression of mothers against decapentaplegic homolog 3 (p-SMAD3) (70.6%) compared to untreated animals. Mor/Telm regimen also elevated p-SMAD7 protein expression as well as m-RNA expression of peroxisome proliferator-activated receptor γ (PPARγ) (3.6 and 3.1 fold, respectively p < 0.05) compared to CCl4 intoxicated group. Histopathological picture of the liver tissue intoxicated with CCl4 revealed marked improvement by Mor/Telm co-treatment. Conclusively, this study substantiated the hepatoprotective effect of Mor/Telm regimen against CCl4-induced liver fibrosis through suppression of TGF-β1/SMAD3, and HDAC2/NF-κB signaling pathways and up-regulation of SMAD7 and PPARγ expression.

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.

Liver-boosting potential: chicory compound-mediated silver nanoparticles for hepatoprotection-biochemical and histopathological insights.

Background: Liver disease is a serious health concern in today's world, posing a challenge to both healthcare providers and pharmaceutical companies. Most synthetic drugs and chemicals cause liver damage accounting for approximately 10% of acute hepatitis and 50% of acute liver failure. Purpose: The present study aimed to evaluate the hepato-protective activity of an extract of chicory formulation assisted by silver nanoparticles against carbon tetra chloride (CCl4)-induced hepatic damage in rat's liver. Methods: Rats of the Wistar strain (Rattus norvegicus) were used to test the in vivo hepato-protective efficacy at various doses. Rats were randomly divided into nine groups, each containing six rats. The groups were as follows: first group (control), second group (CCl4), third group, silymarin (20mg/kg of body weight), fourth group (CCl4+chicory) (1.75mg/kg of b. wt), fifth group (CCl4 + chicory at the dose of 2.35mg/kg), sixth group (CCl4 + chicory of 3.25mg/kg), seventh group (CCl4 +AgNPs 1.75mg/kg of b. wt.), eighth group (CCl4 + AgNPs 2.35mg/kg of body weight), and ninth group (CCl4 + AgNPs 3.25mg/kg of b. wt.). Blood samples were taken 24h after the last administration (i.e., 30th day). The blood samples were analyzed for different serum enzymes such as ALP (alkaline phosphatase), ALT (alanine transaminase), bilirubin (Blr), triglyceride, and cholesterol. Histology liver sections were performed. Results: Treatment with AgNPs and chicory extract showed significant hepato-protective activity in a dose-dependent manner. In three doses, the chicory extract at a rate of 3.25mg/kg of body weight significantly reduced elevated levels of biochemical markers in comparison to CCl4-intoxicated rats. Histology of the liver sections from CCl4-treated rats revealed inflammation of hepatocytes, necrosis, cytoplasmic degeneration, vacuolization, and a deformed central vein. The chicory formulation extract exhibited a remarkable recovery percentage in the liver architecture that was higher than the drug (i.e., silymarin). While treatment with AgNPs also repaired the degenerative changes and restored the normal form of the liver, chicory formulation extract possessed more hepato-protective potential as compared to AgNPs by regulating biochemical and histo-pathological parameters. Conclusion: This study can be used as confirmation of the hepato-protective potential of chicory compounds for possible use in the development programs of drugs to treat liver diseases.

Decalepis hamiltonii root fraction alleviates CCl4 hepatotoxicity in a rat model

BackgroundDecalepis hamiltonii (D. hamiltonii) is Indian folk medicine in herbal preparations, to reduce appetite, and cures dysentery, bronchitis, uterine hemorrhage, and other ailments. ObjectiveThe current investigation focused on the hepatoprotective effect of D. hamiltonii roots fractions against liver damage. Materials and methodsThe current research discussed the fraction from D. hamiltonii root extracts was used. Male Wistar rats (albino strain) were grouped into 4 distinct groups of six animals each. Group I: plain water and vehicle whereas Group II (CCl4 control): CCl4 (1 ml/kg, 20 % v/v in olive oil) over 7 days and vehicle; Over 7 days, Group III received Silymarin 100 mg/kg/day and tap water with 20 % v/v of CCl4, whereas Group IV (treatment group) received DHE 50 mg/kg/day, 100 mg/kg/day, and water. Assessment of biochemical parameters, Mitochondrial modulation, gene expression analysis, and RT-PCR, was used to estimate the protective action of DHEF in CCl4-intoxicated rats. ResultsThe administration of CCl4 increased levels of total bilirubin (0.63 ± 0.97 mg/dl) plasma amino transferases (110.36 ± 1.13 U/L, 86.56 ± 2.41 U/L and 1.51 ± 1.36 mg/dl respectively) which were mitigated by D. hamiltonii treatment. Activity like Lipid peroxidation and content of nitric oxide also augmented, while the antioxidant action measured by GSH (9.64 ± 0.18 U/mg protein), SOD (3.69 ± 0.22 U/mg protein), and CAT (1.47 ± 0.01 U/mg protein) was reduced. Decalepis hamiltonii root provided substantial restoration of GSH (14.92 ± 0.04 nmol/gm protein), SOD (4.20 ± 0.18 U/mg protein), and CAT (2.71 ± 0.04 U/mg protein) levels. In addition, the acute phase reactants stimulated by CCl4 administration enhanced mRNA expressions of IL-6, IL-10, TNF-a, NF-κβ, and COX-2, which were enhanced by D. hamiltonii treatment. ConclusionsIn summary, DHEF protects the liver against CCl4-induced damage, possibly by mitochondrial modulation mechanism. These findings indicate that D. hamiltonii significantly moderates oxidative stress of CCl4-induced hepatotoxicity.

Effect of silymarin on the relative gene expressions of some inflammatory cytokines in the liver of CCl4-intoxicated male rats

The intensive exposure of the liver cells to any type of noxae, such as viruses, drugs, alcohols, and xenobiotics could induce hepatic inflammation through the upregulation of gene expression of several fibrotic and inflammatory mediators. So, our study assessed the role of silymarin on the inflammatory response induced by carbon tetrachloride (CCl4) as an example of xenobiotics on liver tissues in male rats. Forty-eight Wister male rats (weight: 130 ± 10) were housed for 14 days and then divided randomly into six groups: control, SLY: rats received only silymarin orally for 12 weeks (daily), CO: rats were injected with corn oil for 8 weeks (3 times weekly), CCl4: rats were injected with CCl4 solubilized in corn oil for 8 weeks (day by day), Treated: rats received silymarin for 4 weeks after CCl4 injection, Protected: rats received silymarin for 4 weeks before and 8 weeks during CCl4 injection. When the treatment period for the rats was over, they underwent scarification after anesthesia. Then, the sera were extracted from the collected blood for the determination of irisin levels, liver functions, and lipid profiles. Liver tissues were separated for the histopathological examinations, the determination of oxidative stress (OS) parameters content, and the relative gene expression of inflammatory cytokines; nuclear factor kappa (NF)-κB, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, cyclooxygenase (COX)-2, and transforming growth factor beta (TGF-β). The findings showed that silymarin reduced liver inflammation by overcoming the OS process and inflammatory cytokines production which was stimulated by CCl4. These results were confirmed by histopathology of liver tissues.

Virtual Screening of Nrf2 Dietary-Derived Agonists and Safety by a New Deep-Learning Model and Verified In Vitro and In Vivo.

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is an essential regulatory target of antioxidants, but the lack of Nrf2 active site information has hindered discovery of new Nrf2 agonists from food-derived compounds by large-scale virtual screening. Two deep-learning models were separately trained to screen for Nrf2-agonists and safety. The trained models screened potentially active chemicals from approximately 70,000 dietary compounds within 5 min. Of the 169 potential Nrf2 agonists identified via deep-learning screening, 137 had not been reported before. Six compounds selected from the new Nrf2 agonists significantly increased (p < 0.05) the activity of Nrf2 on carbon tetrachloride (CCl4)-intoxicated HepG2 cells (nicotiflorin (99.44 ± 18.5%), artemetin (97.91 ± 8.22%), daidzin (87.73 ± 3.77%), linonin (74.27 ± 5.73%), sinensetin (72.74 ± 10.41%), and tectoridin (77.78 ± 4.80%)), and their safety were demonstrated by an MTT assay. The safety and Nrf2 agonistic activity of nicotiflorin, artemetin, and daidzin were also reconfirm by a single-dose acute oral toxicity study and CCl4-intoxicated rat assay.

Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways.

Oxidative stress plays a critical role in the development of liver disease, making antioxidants a promising therapeutic approach for the prevention and management of liver injuries. The aim of this study was to investigate the hepatoprotective effects of kaempferol, an antioxidant flavonoid found in various edible vegetables, and its underlying mechanism in male Sprague-Dawley rats with carbon tetrachloride (CCl4)-induced acute liver damage. Oral administration of kaempferol at doses of 5 and 10 mg/kg body weight resulted in the amelioration of CCl4-induced abnormalities in hepatic histology and serum parameters. Additionally, kaempferol decreased the levels of pro-inflammatory mediators, TNF-α and IL-1β, as well as COX-2 and iNOS. Furthermore, kaempferol suppressed nuclear factor-kappa B (NF-κB) p65 activation, as well as the phosphorylation of Akt and mitogen-activated protein kinase members (MAPKs), including extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 in CCl4-intoxicated rats. In addition, kaempferol improved the imbalanced oxidative status, as evidenced by the reduction in reactive oxygen species levels and lipid peroxidation, along with increased glutathione content in the CCl4-treated rat liver. Administering kaempferol also enhanced the activation of nuclear factor-E2-related factor (Nrf2) and heme oxygenase-1 protein, as well as the phosphorylation of AMP-activated protein kinase (AMPK). Overall, these findings suggest that kaempferol exhibits antioxidative, anti-inflammatory, and hepatoprotective effects through inhibiting the MAPK/NF-κB signaling pathway and activating the AMPK/Nrf2 signaling pathway in CCl4-intoxicated rats.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Nephroprotective Effect of Fennel (Foeniculum vulgare) Seeds and Their Sprouts on CCl4-Induced Nephrotoxicity and Oxidative Stress in Rats

Functional and nutritional characteristics of seed sprouts and their association with oxidative stress-related disorders have recently become a focus of scientific investigations. The biological activities of fennel seeds (FS) and fennel seed sprouts (FSS) were investigated in vitro and in vivo. The total phenolic content (TPC), total flavonoids (TF), total flavonols (TFF), and antioxidant activity (AOA) of FS and FSS were examined. HPLC and GC-MS analyses for FS and FSS were carried out. Consequently, the nephroprotective and antioxidative stress potential of FS and FSS extracts at 300 and 600 mg kg-1 on CCl4-induced nephrotoxicity and oxidative stress in rats was investigated. In this context, kidney relative weight, blood glucose level (BGL), lipid profile, kidney function (T. protein, albumin, globulin, creatinine, urea, and blood urea nitrogen (BUN)), and oxidative stress biomarkers (GSH, CAT, MDA, and SOD) in the rat's blood as well as the histopathological alteration in kidney tissues were examined. Results indicated that the sprouting process of FS significantly improved TPC, TF, TFL, and AOA in vitro. HPLC identified nineteen compounds of phenolic acids and their derivatives in FS. Thirteen phenolic compounds in FS and FSS were identified, the highest of which was vanillic acid. Six flavonoids were also identified with a predominance of kaempferol. GC-MS indicated that the trans-anethole (1-methoxy-4-[(E)-prop-1-enyl]benzene) component was predominant in FS and FSS, significantly increasing after sprouting. In in vivo examination, administering FS and FSS extracts ameliorated the BGL, triglycerides (TG), total cholesterol (CHO), and their derivative levels compared to CCl4-intoxicated rats. A notable improvement in FS and FSS with 600 mg kg-1 compared to 300 mg kg-1 was observed. A dose of 600 mg FSS kg-1 reduced the TG, CHO, and LDL-C and increased HDL-C levels by 32.04, 24.62, 63.00, and 67.17% compared to G2, respectively. The atherogenic index (AI) was significantly improved with 600 mg kg-1 of FSS extracts. FS and FSS improved kidney function, reduced malondialdehyde (MDA), and restored the activity of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Both FS and FSS extracts attenuated the histopathological alteration in CCl4-treated rats. Interestingly, FSS extract presented better efficiency as a nephroprotection agent than FS extract. In conclusion, FSS can potentially restore oxidative stability and improve kidney function after acute CCl4 kidney injury better than FS. Therefore, FS and FSS extracts might be used for their promising nephroprotective potential and to help prevent diseases related to oxidative stress. Further research on their application in humans is highly recommended.

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.

Clinicobiochemical effects of Phyllanthus niruri and Plantago major on CCl4 Intoxicated rat model

Clinicobiochemical effects of Phyllanthus niruri and Plantago major on CCl4 Intoxicated rat model

Evaluation of Hepatoprotective Activity of Whole Fruit Extracts of Luffa Acutangula. Var. Amara and Rhizome Extracts of Rheum Emodi in CCl4 - Induced Chronic Hepatotoxicity

To investigate the hepatoprotective activity of whole fruit extracts of Luffa acutangula.var. amara and rhizome extracts of Rheum emodi in CCl4 treated rats. The dried powders of L. amara and R. emodi were extracted successively with petroleum ether, ethanol and distilled water. The hepatoprotective capacity of the extract of the whole fruits of L. amara and the rhizomes of R. emodi was analyzed in liver injured CCl4- treated male rats. The present study explored the possibilities of using low doses of both plant extracts (150mg/kg, and 300mg/kg bw, po route) to treat CCL4 intoxicated albino rats in both acute and chronic models of hepatic damage, evident by increased serum levels of glutamate pyruvate transaminase (SGPT), glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), direct bilirubin, total bilirubin, cholesterol and triglycerides, all being implicated in considerable hepatic damage.&#x0D; Histopathological examination in CCl4 treated rats revealed collapse of liver parenchyma with early fibrosis and chronic inflammatory cell infiltration in patchy areas around central vein (Pic.group-2) when compared to the control group. Histopathological and physical examinations also indicated their effectiveness with their dose tolerability and liver protection.&#x0D; Ethanolic and aqueous extracts of the whole fruits of L. amara and rhizomes of R. emodi were indicative of more hepatoprotective properties when compared to the petroleum ether extracts of both plants against CCl4 induced liver damage as confirmed from hepatic serum marker enzyme activities and histopathological studies.

Lipid profiles, hematological parameters and histopathological analysis of CCl4-intoxicated wistar albino rats treated with n-butanol extract of Ficus glumosa leaves

Abstract. Abu MS, Yakubu OE, Onuche JI, Okpe O. 2022. Lipid profiles, hematological parameters and histopathological analysis of CCl4-intoxicated wistar albino rats treated with n-butanol extract of Ficus glumosa leaves. Cell Biol Dev 6: 6-12. This research critically assessed the effect of the n-butanol fraction of methanol extract of Ficus glumosa Delile leaves on serum lipid profile, hematological parameters, and some organ architecture of experimental albino rats intoxicated with carbon tetrachloride. The crude methanol extract was re-dissolved in 300 mL of distilled water and repeatedly partitioned in a separating funnel with 400 mL of n-hexane with vigorous shaking. This process was repeated using other solvents (ethyl acetate, n-butanol, and distilled water), and the n-butanol was selected based on antioxidant potency. A total of 35 albino rats were used. The rats were divided into 7 groups of 5 animals each. Lipid profile, hematological indices, and histopathological analysis were carried out. With the administration of the extract, triacylglycerol and total cholesterol levels in the Carbon tetrachloride-induced but treated rats were significantly (P&lt;0.05) reduced compared to the normal levels, 1.84±0.27 mmol/L, and 0.54±0.11 mmol/L, respectively. In contrast, high-density lipoprotein was relatively increased compared to the normal level, 1.44±0.43 mg/dL. Similarly, packed cell volume, hemoglobin, and white blood cell levels were significantly (P&lt;0.05) reversed to near normal in the extract-treated rats. On the other hand, the histopathological examinations of a liver section of the normal control group showed normal hepatocellular architecture with distinct hepatic cells with a well-conserved central vein. Carbo tetrachloride-induced control group liver showed intense hepatic necrosis with vascular congestion, kupffer cells hyperplasia, vacuolation, and degeneration of normal hepatic cells (hepatic necrosis). However, the induced but treated groups almost normalized the hepatic cells (moderate hepatic necrosis). The findings showed that the n-butanol fraction of F. glumosa could reverse the deleterious effects of CCl4 on lipid profile and hematological parameters with the restoration of the architectural integrities of the liver and kidney of the treated rats.

Evaluation of Antioxidant and Protective Role of Hawthorn Fruit Lyophilized Extract Against Carbon Tetrachloride Toxicity in Rat

This manuscript has aimed to investigate the nephro-hepato protective potential and antioxidant role of lyophilized extract of hawthorn (Crataegus orientalis L) fruit (LEH) against carbon tetrachloride (CCl4) toxicity. The experimental were conducted as; 0.5 ml/kg CCl4, bw), 100 mg/kg LEH bw, 200 mg/kg LEH bw, CCl4 0.5 ml/kg + 100 mg/kg LEH bw and CCl4 0.5 ml/kg + 200 mg/kg LEH bw treated with the extract for 3 weeks. At the end of the experimental treatment, the nephro-hepato protective potential and antioxidant capacity of the LEH was evaluated measuring by liver and kidney damage serum biomarkers, antioxidant defense systems constituents (ADSCs) and malondialdehyde (MDA) content in the erythrocyte, brain, kidney and liver tissues of rats. According to results; liver damage serum enzymes activities and MDA content of the tissues were significantly higher in CCl4 group compared to normal control (NC) whereas; these parameters were significantly lower in extract supplemented groups compared to CCl4 group. According to the resuls, the study results suggest that the LEH supplementations diet restored most of the parameters towards the NC values with fluctuations in the ADSCs. Therefore, it is thought that the extract of hawthorn has antioxidant capacity and hepatoprotective effects against in CCl4-intoxicated rats.

In- vitro Hepatoprotective Action of the Crude Extracts of Luffa amara (Whole Fruit) and Rheum emodi (Rhizomes) in CCl4 Intoxicated Rat Hepatocytes

Aim: The objective of this in-vitro study involves evaluating the protective action of the extracts of L. amara (LA) (whole fruits including seeds) and R. emodi (RE) (rhizomes) at various concentrations on isolated primary rat hepatocytes.&#x0D; Methods: The pulverised dried whole fruits of L. amara (LA) and rhizomes of R.emodi (RE) were extracted successively with petroleum ether (PE), ethanol (EE) and distilled water (AE) and vacuum dried. These extracts of LA petroleum ether (PE), ethanolic (EE) and aqueous (AE) extracts and RE obtained were subjected to in vitro studies at doses of 25, 75, 100, and 150 µg/ml and silymarin (250 µg/ml) in CCl4 (1%) intoxicated primary hepatocytes monolayer cultures the hepatoprotective action of all the extracts of both plants at different doses was carried out using isolated rat hepatocytes which were subjected to CCl4 intoxication followed by estimating/ measuring the changes in serum biochemical markers – SGPT, SGOT, ALP, Total proteins (TP), total bilirubin (TB), albumin (ALB) and triglycerides (TGL).&#x0D; Results: Hepatoprotective activity against CCl4 was demonstrated in the rat primary monolayer hepatocyte culture using MMT assay with the ethanolic extracts of both plants showing more hepatocyte protective action compared to the aqueous and petroleum ether extracts by reducing the elevated serum marker levels. Alcoholic and aqueous extracts were found to express more protective action towards CCl4 intoxicated isolated primary rat hepatocytes in a dose dependant manner.&#x0D; Conclusion: Based on the result, it is suggested that the extract with the most hepatocyte protective action at a dose of 150µg is LA ethanolic extract (viability=88.24%), followed by LA aqueous extract (viability=84.31%), RE ethanolic extract (viability=88.24%) and RE aqueous extract (viability=88.24%) - which are comparable to the reference silymarin with viability at 92.15%. the petroleum ether extracts of both plants showed least hepatic cell viability with LA pet ether extract at 49.02% and RE pet ether extract at 47.85%

Acacia senegal gum attenuates systemic toxicity in CCl4-intoxicated rats via regulation of the ROS/NF-\u03baB signaling pathway

Acacia senegal (AS) gum (Gum Arabic) is a natural emulsifier exudate from the branches and trunk of Acacia trees and it is recognized by the Food and Drug Administration (FDA) agency as a secure dietary fiber. The present research evaluated the systemic oxidative and necroinflammatory stress induced by CCl4 administration and the alleviating effect of AS gum aqueous extract (ASE, 7.5 g/Kg b.w.). The results demonstrated the presence of certain phenolic compounds in ASE, as well as its in vitro potent scavenging ability against ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), NO, and lipid peroxide radicals. Also, the outcomes revealed an improvement in the CCl4-induced liver, lung, brain, and spleen toxicity by reducing the levels of ROS, lipid peroxidation, NO, and the gene expression of NF-κB and its relevant ROS-mediated inflammatory genes. In contrast, the total antioxidant capacity (TAC), as well as the enzymatic and non-enzymatic antioxidants, were significantly upregulated in these organs after the treatment with ASE. These results were confirmed by improving the morphological features of each organ. Therefore, ASE can ameliorate the systemic toxicity caused by CCl4 via regulation of the ROS/NF-κB signaling pathway in the rat organs, which is owed to its phytochemical composition.

Hepatoprotective and Anti-inflammatory Activities of Hydro-alcoholic Extract of Oxalis debilis Kunth. Leaves

This study aimed to investigate hepatoprotective and anti-inflammatory activities of the hydro-alcoholic extract of Oxalis debilis (ODHE) leaves. Acute oral toxicity evaluated ODHE in graded oral doses (100, 500, 1000, 3000, and 5000 mg/kg body weight) in rats. The hepatoprotective activity was evaluated in CCl4 intoxicated rats at 200 and 400 mg/kg body weight doses of ODHE, while anti-inflammatory activity was determined by carrageenan-induced paw edema in rats at 200, 400, 800 mg/kg body weight doses of ODHE. The ODHE was safe at the highest dose of 5000 mg/kg in experimental rats. In hepatoprotective activity, ODHE significantly reduced the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB) levels as compared to the CCl4control group. On the other hand, ODHE showed an anti-inflammatory effect similar to that of the control group in the carrageenan-induced paw edema model. The histopathological findings showed a significant difference between the ODHE (400 mg/kg) and CCl4 groups. The present experiment showed that ODHE has significant hepatoprotective and anti-inflammatory activities. Results confirm the use of O. debilis in folk medicine in the treatment of hepatotoxicity and inflammation.

Targeting ROS/NF-\u03baB signaling pathway by the seedless black Vitis vinifera polyphenols in CCl4-intoxicated kidney, lung, brain, and spleen in rats

Carbon tetrachloride (CCl4) is an abundant environmental pollutant that can generate free radicals and induce oxidative stress in different human and animal organs like the kidney, lung, brain, and spleen, causing toxicity. The present study evaluated the alleviative mechanism of the isolated polyphenolic fraction from seedless (pulp and skin) black Vitis vinifera (VVPF) on systemic oxidative and necroinflammatory stress in CCl4-intoxicated rats. Here, we found that the administration of VVPF to CCl4-intoxicated rats for ten days was obviously ameliorated the CCl4-induced systemic elevation in ROS, NO and TBARS levels, as well as MPO activity. Also, it upregulated the cellular activities of the enzymatic (SOD, and GPx) and non-enzymatic (TAC and GSH) antioxidants. Furthermore, the gene expression of the ROS-related necroinflammatory mediators (NF-κB, iNOS, COX-2, and TNF-α) in the kidney, brain, and spleen, as well as IL-1β, and IL-8 in the lung were greatly restored. The histopathological studies confirmed these biochemical results and showed a noticeable enhancing effect in the architecture of the studied organs after VVPF intake. Thus, this study indicated that VVPF had an alleviative effect on CCl4-induced necroinflammation and oxidative stress in rat kidney, lung, brain, and spleen via controlling the ROS/NF-κB pathway.