Liver Damage In Rats Research Articles

Hepatoprotective effect of Holothuria leucospilota methanolic extract on dimethyl nitrosamine-induced hepatotoxicity in rats.

Complementary medicine is an interesting field for extracting bioactive compounds from various plant and animal sources. The hepatoprotective effect of the methanolic extract of a species of sea cucumber called Holothuria leucospilota in an animal model of liver cancer caused by dimethyl nitrosamine (DMN) was studied. Wistar female rats were randomly divided into five groups (n = 12): control (intact), positive control (received 1% DMN [10 mg/kg/week, intraperitoneally] for 12 weeks), and three treatment groups (received 50, 100, and 200 mg/kg/day H. leucospilota extract orally for 12 weeks along with intraperitoneal administration of 1% DMN [10 mg/kg/week]). In all groups, ultrasound was performed on the liver every week to check its density. Blood sampling and liver isolation were performed on three occasions, at 4, 8, and 12 weeks, to check liver enzymes and the histopathological condition of the liver tissue (every week, four animals from each group were randomly selected). Liver density changes were evident from the eighth week onward in the positive control group. Histopathological results indicated pathologic changes in the positive control group after 4 weeks. The increase in liver enzymes in the positive control group was significantly different from that in the treatment and control groups. We demonstrated the hepatoprotective effect of H. leucospilota on DMN-induced liver damage in rats using biochemical and histological parameters and ultrasonography. More additional research (in silico or invitro) is needed to find the exact mechanism and the main biological compound in H. leucospilota.

Hepatoprotective potential of sciadopitysin against paraquat induced liver damage in rats

Paraquat (PQ) is among the most widely used herbicides in the agriculture sector worldwide and is extremely noxious to both animals and humans. Paraquat exposure damages various organs in the body, particularly the liver. Sciadopitysin (SCD), a biflavonoid that is reported in Ginko biloba leaves, shows diverse biological potentials such as antioxidant and anti-inflammatory effects. The primary focus of this research was to estimate the effects of SCD against PQ-instigated hepatic toxicity in rats. Forty-eight male albino rats were randomly split into 4 groups: control group, PQ (5 mgkg−1) treated group, PQ (5 mgkg−1) + SCD (2 mgkg−1) co-treated group and SCD (2 mgkg−1) only treated group. After 30 days of experimentation, PQ exposure lowered the expression of Nrf-2 and antioxidants genes, while increasing the expression of Keap-1. The activities of antioxidants, including heme oxygenase-1 (HO-1), catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSR), glutathione peroxidase (GPx), and glutathione (GSH) as well as total protein levels, were reduced following PQ administration. Moreover, malondialdehyde (MDA) and reactive oxygen species (ROS) contents were elevated in PQ exposed rats. PQ intoxication also increased the expressions of Bax and Caspase-3, while down-regulating Bcl-2 expressions. Furthermore, PQ exposure induced morphological alterations in the liver. Nevertheless, SCD treatment reduced all PQ-elicited damages in the liver of rats owing to its free radical scavenging potential.

Astragalin Nanoparticles Ameliorates CCl4 - Induced Liver Fibrosis in Rats

Liver plays a vital role in the elimination of xenobiotics that can induce hepatotoxicity in living organisms. Polymeric nanoparticles have evolved recently as an alternative in various industries and are used for their biomedical applications. Astragalin is a least studied flavonoid that has been used in the traditional medicine of Southeast Asia for its healing properties. Hence, in this study we used carbon tetrachloride as a hepatotoxin to induce liver damage. The protective effects of astragalin loaded polymeric nanoparticles on hepatotoxin-induced liver damage in experimental rats were assessed. The results of the assessment indicate that astragalin nanoparticles were effective in protecting the liver from damages induced by carbon tetrachloride. Astragalin nanoparticles formulation is not available in the market. Among existing literature, this is the first ever approach for hepatoprotective effect of astragalin nanoparticles studied.

A Study on the Protective Impact of Resveratrol on Liver Damage in Rats with Obstructive Jaundice.

Obstructive Jaundice (OJ) is a common clinical condition with potential outcomes, including hepatocyte necrosis, bile duct hyperplasia, significant cholestatic liver fibrosis, and, in severe cases, liver failure. Resveratrol (RES), a polyphenol present in grapes and berries, has demonstrated efficacy in improving OJ. However, the precise mechanism of its action remains unclear. In this study, we employed network pharmacology to investigate the underlying molecular mechanism of RES in the treatment of OJ. The targets of RES were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SuperPred, and SwissTargetPrediction database. The targets related to OJ were gathered from the DisGeNET, GeneCards, DrugBank, and Online Mendelian Inheritance in Man (OMIM) databases, and the intersection of these targets was determined using Venny2.1.0. Subsequently, an active component-target network was constructed using Cytoscape software. The Protein-Protein Interaction (PPI) network was generated using the String database and Cytoscape software. Following this, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the Bioconductor platform. Finally, quantitative Real-Time PCR (qRT-PCR), Western Blotting (WB), and Enzyme-Linked Immunosorbent Assay (ELISA) were employed to assess RNA and protein expression levels in related pathways. The findings revealed a selection of 56 potential targets for RES, and a search through the online database identified 2,742 OJ-related targets with overlapping in 27 targets. In the PPI network, mTOR, CYP2C9, CYP1A1, CYP3A4, AHR, ESR1, and HSD17B1 emerged as core targets. KEGG analyses demonstrated that the primary pathways of RES in treating OJ, particularly those related to lipid metabolism, include linoleic acid metabolism, arachidonic acid metabolism, metabolism of xenobiotics by cytochrome P450, lipid and atherosclerosis, tyrosine metabolism, steroid hormone biosynthesis, and pentose and glucuronate interconversions signaling pathways. Furthermore, in vivo experiments indicated that RES significantly ameliorated liver injury induced by Common Bile Duct Ligation (CBDL) in rats with OJ. It lowered serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, reduced liver tissue MDA levels, increased glutathione (GSH) content, and enhanced activity of superoxide dismutase (SOD), alleviating liver damage. Metabolomics analysis revealed that the therapeutic effect of RES in OJ involved alterations in lipid metabolic pathways, hinting at the potential mechanism of RES in treating OJ. ELISA, qRTPCR, and WB analyses confirmed lower expression levels of mTOR, CYP1A1, and CYP2C9 in the RES group compared to the model group, validating their involvement in the lipid metabolism pathway. In conclusion, RES exhibited a protective effect on liver function in rats with OJ. The underlying mechanism appears to be linked to antioxidant activity and modulation of lipid metabolism pathways.

The hepatoprotective effect of 4-phenyltetrahydroquinolines on carbon tetrachloride induced hepatotoxicity in rats through autophagy inhibition

BackgroundThe liver serves as a metabolic hub within the human body, playing a crucial role in various essential functions, such as detoxification, nutrient metabolism, and hormone regulation. Therefore, protecting the liver against endogenous and exogenous insults has become a primary focus in medical research. Consequently, the potential hepatoprotective properties of multiple 4-phenyltetrahydroquinolines inspired us to thoroughly study the influence of four specially designed and synthesized derivatives on carbon tetrachloride (CCl4)-induced liver injury in rats.Methods and resultsSeventy-seven Wistar albino male rats weighing 140 ± 18 g were divided into eleven groups to investigate both the toxicity profile and the hepatoprotective potential of 4-phenyltetrahydroquinolines. An in-vivo hepatotoxicity model was conducted using CCl4 (1 ml/kg body weight, a 1:1 v/v mixture with corn oil, i.p.) every 72 h for 14 days. The concurrent treatment of rats with our newly synthesized compounds (each at a dose of 25 mg/kg body weight, suspended in 0.5% CMC, p.o.) every 24 h effectively lowered transaminases, preserved liver tissue integrity, and mitigated oxidative stress and inflammation. Moreover, the histopathological examination of liver tissues revealed a significant reduction in liver fibrosis, which was further supported by the immunohistochemical analysis of α-SMA. Additionally, the expression of the apoptotic genes BAX and BCL2 was monitored using real-time PCR, which showed a significant decrease in liver apoptosis. Further investigations unveiled the ability of the compounds to significantly decrease the expression of autophagy-related proteins, Beclin-1 and LC3B, consequently inhibiting autophagy. Finally, our computer-assisted simulation dockingonfirmed the obtained experimental activities.ConclusionOur findings suggest that derivatives of 4-phenyltetrahydroquinoline demonstrate hepatoprotective properties in CCl4-induced liver damage and fibrosis in rats. The potential mechanism of action may be due to the inhibition of autophagy in liver cells.

Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme‑oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Influence of milk phospholipids on microstructural changes in rat liver under tetracycline-induced hepatosis

The growing number of cases of adverse effects of medicines on the liver leads to hepatopathology and the development of complications such as cirrhosis, necrosis, liver failure, and liver carcinoma. Therefore, the purpose of this study was to determine the characteristic structural changes in the liver of rats with tetracycline damage and to find out the corrective effectiveness of milk phospholipids. The study performed histological examination of sections from different parts of the liver in experimental rats, which were stained with haematoxylin and eosin according to the conventional method. It was found that in case of artificial modelling of tetracycline-induced hepatosis in rats, the general architecture of the liver is preserved. At the same time, large-scale damage to hepatocytes and the development of fatty and granular dystrophy were recorded in the affected animals. Some of the damaged cells were destroyed, followed by lysis of fragments of the destroyed cells. The described microscopic changes were most pronounced in the areas of the liver under its capsule. As a result, there was partial or complete disorganisation of the liver lobes in all lobes of the organ. The use of milk phospholipids in the form of a biologically active additive “FLP-MD” as a corrective therapy in sick rats prevented the development of hepatocyte dyscomplexity, contributed to a substantial reduction in the count of destroyed cells in a state of dystrophy with isolated cases of disordered organisation of the liver laminae. This suggests a pronounced stimulatory effect of milk phospholipids on the processes of hepatocyte regeneration and repair in tetracycline-induced liver damage in rats. In case of separate administration of a milk phospholipid-based supplement to clinically healthy animals, the microscopic structure of liver samples did not differ from that of the control group. The findings of this study are of practical value for pathologists, clinicians, and therapists in case of development of drug-induced hepatopathology in animals, especially when using tetracycline antibiotics, and for determining the strategy in the treatment of such patients

Protective effect of cinnamon extract against cobalt-induced multiple organ damage in rats.

The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Experimental animal model. The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Cholinergic anti-inflammatory pathway confers protective effects in septic shock rats

Background: Septic shock can lead to multiple organ dysfunction. The cholinergic anti-inflammatory pathway is known to prevent organ damage from infection by modulating the inflammatory response. However, the modulatory capacity of cholinergic anti-inflammatory pathways in septic shock remains unclear. Methods: Cecal ligation and puncture (CLP) was used to establish a rat model of septic shock. Bilateral cervical vagal nerve isolation, dual cervical vagotomy, and vagus nerve stimulation (VNS) were used to inhibit or activate cholinergic anti-inflammatory pathways. Tacrine and α-bungarotoxin groups were used to mimic the activation and shutdown of cholinergic anti-inflammatory pathways. The survival status, hemodynamic indicators, inflammatory cytokine content, and inflammatory response of liver and kidney tissues of the rats were detected. Results: Dual cervical vagotomy significantly exacerbated the hepatic (p &lt; 0.05) and renal (p &lt; 0.05) impairment in septic shock rats relative to the sham-operated group. Tacrine, a cholinergic potentiator, significantly alleviated liver (p &lt; 0.05) and kidney (p &lt; 0.05) damage in septic shock rats. Dual cervical vagotomy significantly promoted the expression of pro-inflammatory factors caused by septic shock in rat liver and kidney tissues (p &lt; 0.05), while Tacrine treatment inhibited the increase of inflammatory factors (p &lt; 0.05). Conclusions: Activation of the cholinergic anti-inflammatory pathway exerts protective effects on multiple organ dysfunction caused by septic shock. The cholinergic enhancer, Tacrine, and VNS effectively ameliorated liver and kidney damage, improved hemodynamic indicators, and enhanced survival rates in septic shock rats.

Whey protein supplementation reduced the liver damage scores of rats fed with a high fat-high fructose diet.

Different functional foods with bioactive nutrients are being explored for the management of NAFLD. Whey proteins are rich in bioactive peptides and are suggested to show antioxidant and anti-inflammatory effects. We aim to test the hypothesis that the whey protein supplementation following a high fat-high fructose (HFHF) diet would protect against liver damage, inflammation, endotoxemia and steatosis in male Wistar rats. 36 rats were randomized into four groups for 8 weeks as the HFHF diet group, HFHF diet and whey protein isolate (WPI-200mg/kg/day) group (HFHF+WPI), control (C) group, and C+WPI (200mg/kg/day) group. Rats fed with a HFHF diet had higher final body weight compared to C and C+WPI groups (p = 0.002). Thus, WPI showed no significant effects for the body weight of rats with a HFHF diet. On the other hand, the HFHF+WPI group had significantly lower abdominal circumference when compared with the HFHF group (p<0,001). Higher serum CRP levels were observed in the groups with a HFHF diet (p<0,001) and WPI supplementation showed no effects on CRP levels. Whey protein supplementation resulted with lower total liver damage score in HFHF+WPI group compared with the HFHF diet group (p<0,001). Conversely, higher liver damage scores were observed with the C+WPI group compared to C group (p<0,001). HFHF diet resulted with higher expression of TLR-4 in the liver meanwhile WPI supplementation showed no effects on liver TLR-4 expression. We observed higher colon Occludin expression in HFHF+WPI and C+WPI groups compared with HFHF and C groups (p<0,001). Our results showed that, whey protein supplementation might help improve liver damage associated with a high fat-high fructose diet and increase the expression of Occludin in the small intestine and colon.

Protective effect of Enicostemma axillare - Swertiamarin on oxidative stress against nicotine-induced liver damage in SD rats

The current investigation was aimed to determine the hepatoprotective benefits of Swertiamarin (ST) administration against nicotine-induced hepatotoxicity in SD rats. A total of 48 adult male SD rats were allocated into six groups using a fully randomised approach. As a control, group I was given oral (PO) normal saline. For 65days, the animals in groups II, III, IV, V and VI received 2.5mg/kg/day of nicotine intraperitoneally (IP), 100mg/kg/day of ST orally (PO), 200mg/kg/day of ST orally (PO), 2.5mg/kg/day of nicotine (IP)+100mg/kg/day of ST (PO), and 2.5mg/kg/day of nicotine (IP)+200mg/kg/day of ST (PO), respectively. Animals were killed on 66thday, liver tissue was removed and used for histopathological analysis as well as biochemical testing (oxidative stress parameters and liver function enzymes). When compared to control animals, the animals in group II showed a substantial rise in their aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine levels (P˂0.001). Furthermore, compared to control animals, these animals displayed enhanced hepatic oxidative stress as indicated by significantly higher Malondialdehyde (MDA) levels (P˂0.001) and lower levels of Catalase (CAT), Glutathione (GSH), Glutathione peroxidase (GSH-Px) and Superoxide dismutase (SOD) (P˂0.001). Further, more histological anomalies were seen in the liver of nicotine-treated rats compared to control rats, including significant vacuolization, poor tissue architecture, the growth of pycnotic nuclei, and dilated sinusoids. Contrary to nicotine-treated rats, the co-administration of ST and nicotine was observed to prevent the abnormalities caused by nicotine (groups V and VI). The results of the current study show that nicotine can seriously harm liver tissue and that swertiamarin can prevent the harmful effects of nicotine on rat liver. Future research is necessary to delve deeply into the mechanisms behind swertiamarin protective impact against nicotine-induced hepatotoxicity.

Fisetin ameliorates methotrexate induced liver fibrosis.

Methotrexate (MTX), a widely used chemotherapeutic and immunosuppressive agent, is associated with hepatotoxicity, leading to liver fibrosis and cirrhosis. This study explores the regenerative and reparative effects of fisetin, a flavonoid with known antioxidant and anti-inflammatory properties, on MTX-induced liver fibrosis in a rat model. Thirty-six male Wistar albino rats were divided into normal, MTX and saline, and MTX and fisetin. Liver injury was induced in the latter two groups using a single intraperitoneal dose of MTX (20 mg/kg). Fisetin (50 mg/kg/day) or saline was administered intraperitoneally for ten days. After sacrifice, liver tissues were subjected to histopathological evaluation and biochemical analyses, including Transforming Growth Factor-β1 (TGF-beta), sirtuins-1 (SIRT-1), malondialdehyde (MDA), cytokeratin 18, thrombospondin 1, and alanine transaminase (ALT) levels. MTX administration significantly increased liver injury markers, including TGF-beta, MDA, cytokeratin 18, thrombospondin 1, and ALT, while reducing SIRT-1 levels. Fisetin treatment attenuated these effects, demonstrating its potential therapeutic impact. Histopathological analysis confirmed that fisetin mitigated MTX-induced hepatocyte necrosis, fibrosis, and cellular infiltration. This study proves that fisetin administration can alleviate MTX-induced liver damage in rats. The reduction in oxidative stress, inflammation, and apoptosis, along with the histological improvements, suggests fisetin's potential as a therapeutic agent against MTX-induced hepatotoxicity. Further investigations and clinical studies are warranted to validate these findings and assess fisetin's translational potential in human cases of MTX-induced liver damage.

Hepatoprotective effect of jojoba oil against lead-induced toxicity in rats

Background Previous investigations showed that jojoba oil exhibited a protective effect against hepatotoxicity caused by different toxicants, however, to the best of our knowledge, no prior research has been done to determine the effectiveness of jojoba oil in protecting against lead toxicity. Objective This study assessed the hepatoprotective properties of jojoba oil against lead toxicity in rats. Materials and methods The study included four groups, each consisting of six Sprague Dawley male rats, and orally administered jojoba oil (JO group), lead acetate (LA group), and lead acetate plus jojoba oil (protective group) Results and conclusion The results showed that lead acetate-induced hepatotoxic effects were revealed by increased serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities with hepatic histomorphological changes. There was a significant increase in serum total cholesterol, triglycerides, and low-density lipoprotein-cholesterol, while levels of high-density lipoprotein-cholesterol significantly declined compared to normal rats. Additionally, lead acetate triggered oxidative damage of hepatocytes, evidenced by a significant increase of malondialdehyde levels and a decrease of reduced glutathione levels and activities of superoxide dismutase and glutathione S-transferase. Administration of lead was associated with a change in the distribution of cells over different cell cycle phases, characterized by a marked increase in the sub G1 cell population and a significant decrease in the G0/G1 cell population. Supplementation of jojoba oil with lead acetate relieved the toxic impacts of lead acetate with an enhancement of the liver enzyme activities, antioxidant status, lipid profile parameters, and histopathological alterations. In conclusion, jojoba oil might be an effective natural product that offers a promising preventive action towards lead-induced liver damage in rats.

Study of Organ Uptake of the New Hepatotropic Paramagnetic Contrast Agent, the Mn(II) Complex of 2-[2-Carboxymethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoethyl]-Aminoethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoacetic Acid (Mn-DTPA-GDOF), In Vivo in Some Experimental Models of Liver Damage in Rats

Study of Organ Uptake of the New Hepatotropic Paramagnetic Contrast Agent, the Mn(II) Complex of 2-[2-Carboxymethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoethyl]-Aminoethyl-(4-Hexadecyloxyphenylcarbamoylmethyl)-Aminoacetic Acid (Mn-DTPA-GDOF), In Vivo in Some Experimental Models of Liver Damage in Rats

Hepatoprotective Effect of Ethanolic Extract of Cnestis ferruginea Roots on Carbon tetrachloride-Induced Liver Damage in Male Rats

Hepatoprotection or antihepatotoxicity is the ability of an agent or chemical to prevent damage to the liver. These hepatoprotective agents mitigate the liver injury caused by the hepatotoxic agents. Therefore, the objective of this paper was to investigate the hepatoprotective effect of ethanolic extract of Cnestis ferruginea roots on carbon tetrachloride (CCl4)-induced liver damage in male rats using appropriate standard methods. A single dose of CCl4 administration significantly (p&lt;0.05) increased the levels of ALT and AST in the positive control group, compared to the negative control group. Also, a significant (p&lt;0.05) increase in the level of ALP and TB was seen in the positive control group relative to the negative control group. While, pre-treatment with either the extract or the standard drug significantly (p&lt;0.05) reduced the levels of hepatic enzymes of serum (ALT, AST and ALP) and TB, when compared with the positive control group. Similarly, the activity of Glutathione-s-transferase (GST), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the liver of untreated rats (induced with CCl4)was significantly decreased (p&lt;0.05) in comparison with the rats treated with the extracts and the standard drug. Thus, treatment of the CCl4 -induced rats with the extracts for fourteen days resulted in the reversal of the CCl4- induced liver damage in the rats with the high dose (200 mg/kg) giving the best result which was comparable with the standard drug. Therefore the ethanolic extract of C. ferruginea roots protects the liver against CCl4 -induced oxidative stress.

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.

Protective effect of intermittent hypobaric hypoxia against radiation-induced liver damage in Sprague-Dawley rats.

Without timely and effective interventions or treatments, radiation-induced liver damage (RILD) can lead to serious consequences for the patients and their families. To investigate the protective effect of intermittent hypobaric hypoxia preconditioning (IHHP) in RILD. Male adult SD rats were randomly divided into 8 groups including one control group, one only irradiation group and other experimental groups. Blood routine tests and liver function tests were all assessed with abdominal venous blood. Moreover, hematoxylin eosin (HE) staining and immunohistochemistry assay were used to detect the histopathological changes and expressions of transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α) and hypoxia-inducible factor 1α (HIF-1α) in radiated liver sections. Blood routing tests showed that RBC, WBC and Hb were all significantly increased while the differences of these results between different groups with same simulated altitude were approximate. However, liver function in the IHHP plus irradiation at 4000 m group was significantly decreased (P< 0.05) compared to only irradiation groups, and the manifestation of HE and lower positive expression of TNF-α showed improved histopathological changes in the liver section. Furthermore, no significant difference of HIF-1α expression between any two groups treated with IHHP was observed. IHHP at the altitude of 4000 m group could alleviate the radioactive liver damage by downregulating TNF-α and less strong positive expression of TGF-β1. Furthermore, patients exposed to radiation might benefit from this treatment to prevent or reduce the RILD.

Therapeutic potential of caffeic acid and coumarin in modifying aluminum-induced hepatic injury in Wistar rats

Antioxidants and phenolic compounds have always been tested as chemoprotective agents to regulate disease progression related to oxidative stress. Through this study, we investigate the possible corrective effects of caffeic acid and coumarin against aluminum- (Al-) induced stress response and liver damage in rats. Male Wistar rats were divided into four groups (10 rats per group), cotreated with caffeic acid (30 mg kg-1) and coumarin (5 mg kg-1) and exposed to aluminum (60 mg kg-1) for 45 days. Al induced significant alterations in body and liver weight over time. It also led to a marked increase in plasma levels of transaminases (aspartate aminotransferase and alanine aminotransferase), alkaline phosphatase, and lactate dehydrogenase. Additionally, there was a substantial change in the lipid profile, characterized by elevated levels of triglycerides and total cholesterol in both serum and liver. Furthermore, the LDL-c level and the HDL-c/total cholesterol ratio in serum were also affected. In contrast, the levels of HDL-c in serum and phospholipids in liver tissues were reduced. The results of this study also showed increased levels of TBARS, protein carbonyls, nitrates/nitrites, and TNF-α. Conversely, the activity of antioxidant enzymes (catalase, GP-x, and SOD) was reduced. These altered parameters were restored after treating rats with caffeic acid and coumarin. Our study strongly suggests that caffeic acid and coumarin possess antioxidant properties and hepatoprotective capacity by attenuating aluminum toxicity-induced liver damage.

A Comparison of the Protective Effect of Pyridoxine and N-Acetylcysteine in Paracetamol Induced Hepatotoxicity in Rats

Paracetamol is a common over the counter drug. Paracetamol-induced hepatotoxicity results in over 300,000 hospitalizations each year and accounts for up to 42% of all cases of acute liver failure. N-acetylcysteine (NAC) is a potential antidote to manage paracetamol toxicity. Objective: To investigate the effects of pyridoxine, alone and in combination with NAC in repairing paracetamol-induced liver damage in male Wister rats. Methods: A single oral dose of paracetamol (650 mg/kg) was administered to Wistar rats to induce hepatotoxicity. The hepato-protective effects of NAC at a dose 300 mg/kg, and pyridoxine (200 mg/kg) were evaluated using standard liver function tests and histopathological along with serum glutathione levels. Results: The administration of pyridoxine and NAC resulted in a significant decrease in AST, ALT, and total bilirubin levels and the reversal of histopathological changes. Conversely, administering NAC and pyridoxine in combination yielded significant changes except for the glutathione level. Conclusions: The study concluded that pyridoxine may be used as a potential hepatoprotective drug in paracetamol-induced hepatotoxicity. In combination with NAC, it showed protective effects in paracetamol-induced hepatoxicity.