Liver Damage In Rats Research Articles

Carvacrol prevents acrylamide-induced oxidative and inflammatory liver damage and dysfunction in rats.

Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1β, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.

BORİK ASİT SIÇANLARDA SİKLOFOSFAMİDİN NEDEN OLDUĞU KARACİĞER HASARINI İYİLEŞTİRİR

Introduction: The aim of the current study was to look into any potential ameliorative benefits of boric acid on liver damage in rats caused by cyclophosphamide (CTX). 
 Materials and Methods: Four groups; control, boric acid, CTX, and boric acid + CTX, were created. Female Wistar albino rats were given daily injections of CTX (75 mg/kg) to create the liver damage model. Cyclophosphamide (75 mg/kg) was administered intraperitoneally, and boron (1.3 g/rat/day) was administered by gavage every day for two weeks in the boric acid+CTX group. The histopathological changes were evaluated in ovarian tissue staining with hematoxylin and eosin, masson tricrom, and periodic acid Schiff. We assessed ovarian tissue enzyme activity as malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). 
 Results: Images in the boric acid+CTX group had lower histological evaluations than those in the CTX group under the light microscope. According to the findings, boric acid reduced the levels of malondialdehyde (MDA) in the liver tissues. Additionally, boric acid improved the actions of oxidative stress indicators to reduce oxidative stress brought on by CTX and upregulated antioxidant parameters.
 Conclusion: In conclusion, our study have demonstrated that CTX- induced liver injury can be alleviated by reducing the tissue MDA levels, increasing the liver’s SOD, GSH-Px, and CAT activities. In order to reduce the liver damage caused by CTX, boric acid may be administered as a dietary supplement or functional food.

Hepatoprotective Effect of Herbal Medicinal Plant Extract against Paracetamol Induced Liver Injury in Rats

The purpose of this study was to examine the hepatoprotective efficacy of Whole plant extract of Adiantum capillus against Paracetamol induced liver damage in rats. Wistar albino rats were orally fed 500 mg/kg of body weight of Methanolic and Acetonic extract of Adiantum capillus Whole plant, with Silymarin serving as the reference. By restoring functional parameters, physical parameters, biochemical parameters, and decreasing blood enzymes alkaline phosphatase (ALP) and total bilirubin (TBL) in the selected animal, the methanolic and Acetonic extracts exhibited a potent hepatoprotective effect. The plant's chemical composition includes, among others, alkaloids, flavonoids, glycosides, steroids, terpenoids, phenolics, and saponins. The overall experimental data suggest that bioactive phytoconstituents, such as flavonoids and alkaloids, present in the Methanolic and Acetonic extracts of Adiantum capillus plant may be responsible for the plant's significant hepatoprotective effect. The results thus support the use of Adiantum capillus plant as a hepatoprotectant.

Hepatoprotective effect of methanol extract of Agave americana leaves on paracetamol induced hepatotoxicity in Wistar albino rats

BackgroundEthiopians locally treat liver illnesses with A. Americana. Available literature demonstrates this. However, there are few in-vivo investigations that provide supporting data. The aim of this study was to evaluate the hepatoprotective effects of methanolic extract of Agave americana leaves on rat liver damage caused by paracetamol.MethodsThe acute oral toxicity test was conducted in accordance with OECD-425 recommendations. The approach outlined by Eesha et al. (Asian Pac J Trop Biomed 4:466-469, 2011) was used to test the hepatoprotective activity. Wistar male rats weighing between 180 and 200 g were used, and six groups with seven animals each were formed. Group I received treatment with gum acacia (2%) at a dose of 2 ml/kg p.o. daily for 7 days. Rats in group II were treated with 2% gum acacia orally daily for seven days along with a single dose of paracetamol (2 mg/kg) p.o. on 7th day. Silymarin (50 mg/kg) was given orally to Group III for 7 days. Plant extract doses of 100 mg/kg, 200 mg/kg, and 400 mg/kg were administered orally to Groups IV -VI for seven days, respectively. All rats in groups III-VI were treated with paracetamol (2 mg/kg) 30 min following extract administration. Blood samples were obtained from the cardiac puncture after paracetamol had been used for 24 h to induce toxicity. Serum biomarkers (AST, ALT, ALP, and total bilirubin) were estimated. A histopathological investigation was also done.ResultsNo toxicity symptoms or animal fatalities were recorded during the acute toxicity study. The values of AST, ALT, ALP, and total bilirubin were all substantially raised by paracetamol. Significant hepatoprotective effects were obtained by pretreatment with A. americana extract. Histopathological examination of the liver tissues of paracetamol control group represented the presence of marked foci of mononuclear infiltration in the hepatic parenchyma tissue, sinusoid, and around central vein, as well as disorganization of hepatic plates, necrosis, and fatty changes of hepatocytes. Pretreatment with A. americana extract reversed these alterations. Results of the methanolic extract of A. americana were comparable to Silymarin.ConclusionThe current investigation supports the hepatoprotective properties of Agave americana methanolic extract.

Arginine vasopressin deficiency and conivaptan (a V1a-V2 receptor antagonist) treatment reverses liver damage and fibrosis in rats with chronic portocaval anastomosis.

Arginine vasopressin (AVP) is a naturally occurring hormone synthesized in the hypothalamus. AVP demonstrates pro-fibrotic effects as it stimulates hepatic stellate cells to secrete transforming growth factor-β (TGF-β) and collagen. Previous work in liver cirrhotic (CCL4 -induced) hamsters demonstrated that AVP deficiency induced by neurointermediate pituitary lobectomy (NIL) can restore liver function. Therefore, we hypothesized that liver fibrosis would decrease in portocaval anastomosis (PCA) rats, which model chronic liver diseases, when they are treated with the V1a-V2 AVP receptor antagonist conivaptan (CV). In this study, changes in liver histology and gene expression were analysed in five experimental groups: control, PCA, NIL, PCA + NIL and PCA + CV, with NIL surgery or CV treatment administered 8 weeks after PCA surgery. Body weight gain was assessed on a weekly basis, and serum liver function, liver weight and liver glycogen content were assessed following euthanasia. Most PCA-induced phenotypes were reverted to normal levels following AVP-modelled deficiency, though hypoglycemia and ammonium levels remained elevated in the PCA + CV group. Liver histopathological findings showed a significant reversal in collagen content, less fibrosis in the triad and liver septa and increased regenerative nodules. Molecular analyses showed that the expression of fibrogenic genes (TGF-β and collagen type I) decreased in the PCA + CV group. Our findings strongly suggest that chronic NIL or CV treatment can induce a favourable microenvironment to decrease liver fibrosis and support CV as an alternative treatment for liver fibrosis.

Investigation of hepatoprotective effect of aqueous extract of calliste-mon viminalis (AECV) in paracetamol-induced liver toxicity in male rats

The current study was performed to investigate the hepatoprotective potential of Callistemon viminalis (AECV) on paracetamol –induced liver damage in male rats. Twenty-four male Wister rats (150–200 gm) were divided into 4 groups (6 animals each). Paracetamol was given at a dose of 2g/kg once daily for one week to induce liver injury, while AECV was administered via oral gavage at a dose of 200mg/kg B.W. for 4 weeks. Silymarin was given orally as reference hepatoprotective drug at a dose of 100mg/kg B.W. Liver enzymes such as ALT, AST, ALP, and total bilirubin were used to determine the level of hepatic injury recovery. SOD and CAT were measured as antioxidant enzymes. Both AECV and silymarin were successful in preventing the liver damage caused by paracetamol in male rats. The extract's hepatoprotective properties were demonstrated by a significant decrease in the blood enzymes ALT, AST, ALP, and TB and an increase in the antioxidant enzymes SOD and CAT.

Phytochemical analysis and in vitro and in vivo antioxidant properties of Plagiorhegma dubia Maxim as a medicinal crop for diabetes treatment

In traditional medicine, Plagiorhegma dubia Maxim (PD) is used to treat diabetes, irritability, insomnia, high fever, and coma. In this study, to identify the components in PD, we first performed three preliminary phytochemical tests, which were all positive for the presence of alkaloids. Next, we evaluated the total alkaloid content and performed 13 different in vitro antioxidant experiments for three solvent extracts of PD. According to the results, the methanol extract was selected for further research. Ultra-performance liquid chromatography with electrospray ionization Orbitrap mass spectrometry was used to identify 41 compounds in the methanol extract. Thirty-eight of these compounds were alkaloids, and the main components were magnoflorine, berberrubine, and betaine. Addition of the methanol extract to cooking oil increased the stability against oxidation and greatly reduced the peroxide value. Cell viability and oral acute toxicity studies in mice indicated that the methanol extract was relatively non-toxic. Histopathological examination and biochemical analysis showed that the methanol extract was protective against liver damage in rats induced by d-galactosamine. The methanol extract also showed a good antidiabetic effect for streptozotocin-induced diabetes in rats, where it lowered blood sugar levels and protected vital organs against damage. Lipid profile parameters and oxidative stress parameters also improved. The therapeutic effects towards diabetes and liver damage were attributed to the ability of the three main components in the methanol extract to resist oxidative stress. Our results show that the alkaloid-rich methanol extract of PD is potential candidate for treatment of diseases associated with oxidative imbalances. This understanding of the hepatoprotective effect and antidiabetic activity of PD provides new insight for its use as a substitute for Coptis chinensis and establishes a foundation for development of PD as an economic crop.

Tempol Alters Antioxidant Enzyme Function, Modulates Multiple Genes Expression, and Ameliorates Hepatic and Renal Impairment in Carbon Tetrachloride (CCl4)-Intoxicated Rats

The purpose of this study was to determine the effect of the superoxide dismutase mimic compound “tempol” on liver and renal damage in Long Evans male rats administered with carbon tetrachloride (CCl4). Methods: The antioxidant enzyme activity and oxidative stress parameters were investigated in the liver, kidney, and plasma tissues. Histological examination of the liver and kidney sections affirmed inflammatory cell infiltration, collagen deposition, and iron deposition. RT-PCR was also employed to evaluate the expression of oxidative stress and inflammatory genes. Results: The CCl4-administered rats exhibited increased plasma activities of ALT, AST, and ALP compared to the control rats. The tempol treatment in the CCl4-administered rats significantly lowered ALT, AST, and ALP enzyme activities compared to the CCl4 group. Oxidative stress parameters, such as the MDA, NO, and APOP levels in various tissues of the CCl4-administered rats, showed increased concentrations, whereas tempol significantly lowered the level of oxidative stress. Moreover, CCl4 administration decreased the antioxidant enzyme activities, which were further significantly restored by the tempol treatment. The control rats that underwent treatment with tempol did not present with any abnormality or toxicity. Furthermore, the tempol treatment in the CCl4-administered rats increased Nrf-2-HO-1-mediated gene expression and enhanced related antioxidant enzyme gene expressions. The tempol treatment in the CCl4-administered rats also decreased anti-inflammatory gene expressions in the liver. In histological sections of the liver, CCl4 increased inflammatory cell infiltration, collagen deposition, and iron deposition, which were reduced significantly due to the tempol treatment. Conclusion: The results of this investigation revealed that tempol could protect against liver and kidney damage in CCl4-administered rats by modulating antioxidant gene expressions and restoring antioxidant defense mechanisms.

The effect of miR-155-5p on M1 polarization of Kupffer cells and immune response during liver transplantation through regulating the expression of KDM5D.

To explore the effect and its specific mechanism of miR-155-5p on M1 polarization of Kupffer cells (KCs) and immune response in liver transplantation (LT) through KDM5D. Primary KCs were isolated from Wistar rats and identified by cell culture, ink-swallowing test and flow cytometry. The cells identified as KCs were induced into LT acute rejection (AR) model cells by LPS/IFN-γ, flow cytometry was used for cell sorting and apoptosis detection. Enzyme-linked immunosorbent assay (ELISA) kit was used to detect the levels of inflammatory factors, macrophages and liver function markers. RT-qPCR detected the expression of miR-155-5p and KDM5D mRNA. The protein expression of KDM5D was detected by Western blot. Dual luciferase reporter gene experiment verified the targeting relationship between miR-155-5p and KDM5D. The separated KCs adhered after being cultured for 24h, had pseudopodia and phagocytosis, and the proportion of F4/80 positive cells was more than 90%. The expression of miR-155-5p was increased in LPS/IFN-γ-induced KCs. And knockdown of miR-155-5p inhibited H3K4me3 and H3K27me3 of TNF-α promoter, M1 polarization of KCs and the immune response of AR model cells by upregulating KDM5D. In animal experiments, knockdown of miR-155-5p was found to inhibit liver damage and immune response in rats with allogeneic orthotopic LT. These results confirmed that miR-155-5p inhibited M1 polarization of KCs induced by LPS/IFN-γ, thereby alleviating AR and liver function impairment after LT by upregulating KDM5D.

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.

Lutein Prevents Liver Injury and Intestinal Barrier Dysfunction in Rats Subjected to Chronic Alcohol Intake

Chronic alcohol intake can affect both liver and intestinal barrier function. The goal of this investigation was to evaluate the function and mechanism of lutein administration on the chronic ethanol-induced liver and intestinal barrier damage in rats. During the 14-week experimental cycle, seventy rats were randomly divided into seven groups, with 10 rats in each group: a normal control group (Co), a control group of lutein interventions (24 mg/kg/day), an ethanol model group (Et, 8-12 mL/kg/day of 56% (v/v) ethanol), three intervention groups with lutein (12, 24 and 48 mg/kg/day) and a positive control group (DG). The results showed that liver index, ALT, AST and TG levels were increased, and SOD and GSH-Px levels were reduced in the Et group. Furthermore, alcohol intake over a long time increased the level of pro-inflammatory cytokines TNF-α and IL-1β, disrupted the intestinal barrier, and stimulated the release of LPS, causing further liver injury. In contrast, lutein interventions prevented alcohol-induced alterations in liver tissue, oxidative stress and inflammation. In addition, the protein expression of Claudin-1 and Occludin in ileal tissues was upregulated by lutein intervention. In conclusion, lutein can improve chronic alcoholic liver injury and intestinal barrier dysfunction in rats.

Heat-Killed Enterococcus faecalis Inhibit FL83B Hepatic Lipid Accumulation and High Fat Diet-Induced Fatty Liver Damage in Rats by Activating Lipolysis through the Regulation the AMPK Signaling Pathway

Continuous consumption of high-calorie meals causes lipid accumulation in the liver and liver damage, leading to non-alcoholic fatty liver disease (NAFLD). A case study of the hepatic lipid accumulation model is needed to identify the mechanisms underlying lipid metabolism in the liver. In this study, the prevention mechanism of lipid accumulation in the liver of Enterococcus faecalis 2001 (EF-2001) was extended using FL83B cells (FL83Bs) and high-fat diet (HFD)-induced hepatic steatosis. EF-2001 treatment inhibited the oleic acid (OA) lipid accumulation in FL83B liver cells. Furthermore, we performed lipid reduction analysis to confirm the underlying mechanism of lipolysis. The results showed that EF-2001 downregulated proteins and upregulated AMP-activated protein kinase (AMPK) phosphorylation in the sterol regulatory element-binding protein 1c (SREBP-1c) and AMPK signaling pathways, respectively. The effect of EF-2001 on OA-induced hepatic lipid accumulation in FL83Bs enhanced the phosphorylation of acetyl-CoA carboxylase and reduced the levels of lipid accumulation proteins SREBP-1c and fatty acid synthase. EF-2001 treatment increased the levels of adipose triglyceride lipase and monoacylglycerol during lipase enzyme activation, which, when increased, contributed to increased liver lipolysis. In conclusion, EF-2001 inhibits OA-induced FL83B hepatic lipid accumulation and HFD-induced hepatic steatosis in rats through the AMPK signaling pathway.

The effect of vitamin C supplementation on favipiravir-induced oxidative stress and proinflammatory damage in livers and kidneys of rats

Background: Favipiravir (FPV), an effective antiviral agent, is a drug used to treat influenza and COVID-19 by inhibiting the RNA-dependent RNA polymerase (RdRp) of RNA viruses. FPV has the potential to increase oxidative stress and organ damage. The purpose of this study was to demonstrate the oxidative stress and inflammation caused by FPV in the liver and kidneys of rats, as well as to investigate the curative effects of vitamin C (VitC). Methods: A total of 40 Sprague–Dawley male rats were randomly and equally divided into the following five groups: 1st; Control, 2nd; FPV = 20 mg/kg, 3rd; FPV = 100 mg/kg, 4th; FPV = 20 mg/kg + VitC (150 mg/kg), and 5th; FPV = 100 mg/kg + VitC (150 mg/kg) groups. Rats were given either FPV (orally) or FPV plus VitC (intramuscular) for 14 days. Rat blood, liver, and kidney samples were collected at 15 days to be analyzed for oxidative and histological changes. Results: FPV administration resulted in an increase in proinflammatory cytokines (TNF-α and IL-6) in the liver and kidney, as well as oxidative and histopathologic damage. FPV increased TBARS levels significantly (p < .05) and decreased GSH and CAT levels in liver and kidney tissues but had no effect on SOD activity. VitC supplementation significantly reduced TNF-a, IL-6, and TBARS levels while increasing GSH and CAT levels (p < .05). Furthermore, VitC significantly attenuated FPV-induced histopathological alterations associated with oxidative stress and inflammation in the liver and kidney tissues (p < .05). Conclusion: FPV caused liver and kidney damage in rats. In contrast, co-administration of FPV with VitC improved FPV-induced oxidative, pro-inflammatory, and histopathological changes.

Angiotensin converting enzyme (ACE) inhibitors activity from purified compounds Fructus Phaleria macrocarpa (Scheff) Boerl

BackgroundMahkota Dewa [Phaleria macrocarpa (Scheff) Boerl.] fruit in vitro and in- vivo can decrease and prevent elevation of the blood pressure, lower plasma glucose levels, possess an antioxidant effect, and recover liver and kidney damage in rats. This study aimed to determine the structure and inhibitory activity of angiotensin-converting enzyme inhibitors (ACE) from the Mahkota Dewa fruit.MethodsThe fruit powder was macerated using methanol and then partitioned by hexane, ethyl acetate, n-butanol, and water. The fractions were chromatographed on the column chromatography and incorporated with TLC and recrystallization to give pure compounds. The structures of isolated compounds were determined by UV-Visible, FT-IR, MS, proton (1H-NMR), carbon (13C-NMR), and 2D-NMR techniques encompassing HMQC and HMBC spectra. The compounds were evaluated for their ACE inhibitory activity, and the strongest compound was determined by the kinetics enzyme inhibition.ResultsBased on the spectral data, the isolated compounds were determined as 6,4-dihydroxy-4-methoxybenzophenone–2-O-β-D-glucopyranoside (1), 4,4′-dihydroxy-6-methoxybenzophenone-2-O-β-D-glucopyranoside (2) and mangiferin (3). IC50 values of the isolated compounds 1, 2 and 3 were 0.055, 0.07, and 0.025 mM, respectively.ConclusionThe three compounds have ACE inhibitor and mangiferin demonstrated the best ACE inhibitory activity with competitive inhibition on ACE with the type of inhibition kinetics is competitive inhibition.

β-Sitosterol mitigates hepatocyte apoptosis by inhibiting endoplasmic reticulum stress in thioacetamide-induced hepatic injury in γ-irradiated rats.

Liver damage in rats was induced by TAA (150 mg/kg I.P twice a week/3 weeks) and γ-irradiation (single dose 3.5 Gy) and treated with βS (20 mg/kg daily for 30 days). Serum aminotransferase activity, lipid profile and lipid metabolic factors were measured beside liver oxidative stress and inflammatory markers. Moreover, the hepatic expression of ER stress markers (inositol-requiring enzyme 1 alpha (IRE1α), X-box-binding protein 1 (XBP1) and CCAAT/enhancer binding protein homologous protein (CHOP) and apoptotic markers were detected together with histopathological examination. βS diminished the aminotransferase activity, the oxidative stress markers as well as the inflammatory mediators. Furthermore, βS lowered the circulating TG and TC and the hepatic lipotoxicity via the suppression of lipogenesis (Srebp-1c) and improved the β-oxidation (Pparα and Cpt1a) together with the mitochondrial biogenesis (Pgc-1 α). Moreover, the upregulated levels of ER stress markers were reduced upon treatment with βS, which consequently attenuated hepatic apoptosis. βS relieves hepatic injury, ameliorates mitochondrial biogenesis, and reduces lipotoxicity and apoptosis via inhibition of CHOP and ER stress response.

Protective Effects of Crocin Against Methotrexate-Induced Hepatotoxicity in Adult Male Albino Rats: Histological, Immunohistochemical, and Biochemical Study.

Among the many known adverse effects of methotrexate (MTX), hepatotoxicity stands out as a major drawback that limits its therapeutic applicability. There is growing evidence that crocin has antioxidant, anti-hyperglycemic, cardioprotective, and anti-inflammatory effects. This study's aim is to evaluate the potential protective effect of crocin against MTX-induced liver damage in rats using biochemical, histological, and immunohistochemical analyses. Twenty-four adult male albino rats were split into four groups at random (six rats/group) as follows: normal control (saline, intraperitoneal (i.p.) injections), crocin-treated (100 mg/kg dailyfor 14 days, i.p.), MTX-treated (20 mg/kgsingle i.p. injectionon day 15), and crocin/MTX-treated groups (crocin 100 mg/kg/dayfor 14 days, i.p.+ MTX 20 mg/kgsingle i.p. injectionon day 15). On day 16 of the experiment, blood and tissue specimens were used to assess the liver functions, oxidative stress markers, transforming growth factor beta 1 (TGF-β1), caspase-3, BCL-2-associated X protein (BAX), and B-cell lymphoma 2 (BCL-2) expression. The results of the current research revealed the protective actions of crocin against MTX-induced hepatotoxicity. Our results showed that crocin possesses antioxidants (decrease malondialdehyde (MDA), increase glutathione (GSH) levels, and enhance catalase (CAT) and superoxide dismutase (SOD) enzymatic activity), anti-fibrotic (decrease TGF-β1), and anti-apoptotic (decrease BAXand caspase-3 expression while increase BCL-2) actions in liver. Moreover, crocin administration along with MTX restores the normal histological structure of hepatic tissues. Thedata presented in the current study using an in vivo animal model supportthe notion that crocin should be further studied in humans to assess its potential hepatoprotective effects againstMTX-induced liver damage.

Pharmacological correction of white rats liver damage in aflatoxin B1 poisoning

Aflatoxin B1 is a hepatotoxic and hepatocarcinogenic compound. It is one of the common mycotoxins that causes various pathological conditions in humans and animals such as acute and chronic liver damage, neurological disorders, neoplasms and reproductive disorders.The present work was aimed to study the preventive effect of a dietary supplement based on milk thistle flour, succinic acid, bentonite, probiotic strain B. subtilis, vitamins A and E in experimental aflatoxicosis of laboratory animals. The experiments were carried out on 24 white rats, divided according to the principle of analogues into 4 groups. The first group - biological control, the second group - toxic control, the third and fourth groups were given medications against mycotoxin. White rats were injected with aflatoxin B1 with food at a dose of 500 µg/kg for 10 days. The treatments effectiveness was assessed by clinical signs of experimental animals and hemato-biochemical analysis. The level of exposure to aflatoxin B1 was evaluated by the state of the liver. The use of a biologically active additive significantly reduced the toxic effect of aflatoxin B1 on the animal organism, prevented a decrease in the amount of hemoglobin, leukocytes and erythrocytes, an increase in platelets, the activity of aminotransferases (aspartate aminotransferase and alanine aminotransferase), alkaline phosphatase and malonic daldehyde. There were no pathoana tomic changes in the internal organs of animals receiving a biologically active supplement.The results of the experiment indicate the high therapeutic efficacy of the biologically active additive used in aflatoxicosis, due to the multicomponent composition.

Evaluation of the Possible Protective Role of Nobiletin against Arsenic-Induced Liver Damage in Male Albino Rats.

Arsenic (As) is a toxic contaminant present in organic and inorganic forms in the environment. Nobiletin (NOB) is a polymethoxy flavone that has recently gained substantial consideration due to its curative impacts. The present experiment was conducted to assess the hepatoprotective efficiency of NOB on As-generated hepatotoxicity. Twenty-four adult rats were equally distributed into four groups and designated as control, As (50 mg/kg)-treated, As + NOB (50 mg/kg and 25 mg/kg, respectively), and NOB (25 mg/kg)-treated groups. After 30 days, experimental animals were decapitated, then blood and tissue samples were collected for further analysis. The group treated with As showed a significant decrease in the activity of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), glutathione reductase (GSR), and total antioxidant status (TAS), and a substantial increase in the accumulation of As in liver tissues, levels of total oxidant status (TOS), hydrogen peroxide (H2O2), and lipid peroxidation (TBARS). Significant increases in alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) levels were observed in As-treated rats. Moreover, nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, interleukin (IL)-6, and cyclo-oxygenase (COX)-2 activity, as well as the levels of pro-apoptotic markers (Bax, Caspase-3, and Caspase-9) were increased on exposure to As. In contrast, the anti-apoptotic marker (Bcl-2) level was significantly decreased. As administration showed a significant disturbance in hepatic tissue histology. However, cotreatment of NOB with As considerably increased the antioxidant enzyme activity, with a noteworthy reduction in the deposition of As in hepatic tissues, TBARS, and H2O2 levels. NOB-administrated rats showed considerable recovery in terms of inflammation, apoptosis, and histological damage. Hence, NOB can be considered a useful curative compound due to its medicinal properties against As-prompted hepatotoxicity.

Concomitant Sub-Chronic Administration of Small-Size Gold Nanoparticles Aggravates Doxorubicin-Induced Liver Oxidative and Inflammatory Damage, Hyperlipidemia, and Hepatic Steatosis.

This study examined the effect of gold nanoparticles (AuNPs) on doxorubicin (DOX)-induced liver damage and steatosis in rats and tested its effect mechanism. Wistar male rats were divided into four groups (each of eight rats) as control, AuNPs (50 µL of 10 nm), DOX (15 mg/kg; 3 mg/kg/week), and DOX + AuNPs-treated rats. DOX is known to induce fasting hyperglycemia and hyperinsulinemia in treated rats. Individual treatment of both DOX and AuNPs also promoted liver damage, increased circulatory levels of ALT and AST, and stimulated serum and liver levels of TGs, CHOL, LDL-c, and FFAs. They also stimulated MDA, TNF-α, and IL-6, reduced GSH, SOD, HO-1, and CAT, upregulated mRNA levels of Bax and caspases-3 and -8 and downregulated mRNA levels of Bcl2 in the livers of rats. However, while DOX alone reduced hepatic levels of PPARα, both AuNPs and DOX stimulated mRNA levels of SREBP1, reduced the mRNA, cytoplasmic and nuclear levels of Nrf2, and increased mRNA, cytoplasmic, and nuclear levels of NF-κB. The liver damage and the alterations in all these parameters were significantly more profound when both AuNPs and DOX were administered together. In conclusion, AuNPs exaggerate liver damage, hyperlipidemia, and hepatic steatosis in DOX-treated rats by activating SREBP1 and NF-κB and suppressing the Nrf2/antioxidant axis.

Melatonin improves liver and pancreatic tissue injuries in diabetic rats: role on antioxidant enzymes.

Melatonin (Mel) is an indolamine mainly synthesized by the pineal gland and many other organs. It plays an important role in scavenging free radicals and stimulating antioxidant enzymes. The goal of this study was to investigate the effect of Mel and/or insulin treatment on oxidative liver and pancreas injuries in diabetic rats. Male Wistar albino rats were assigned into 5 groups. Group I: control animals. Group II: diabetes was induced via a single dose of STZ (60mg/kg) administered intraperitoneally. Group III: diabetic rats treated with Mel (10mg/kg/day). Group IV: diabetic rats given insulin (6U/kg) subcutaneously. Group V: diabetic rats that received insulin and Mel at the same dose and time. After 12 weeks of the experiment, the animals were decapitated, liver and pancreas tissues were collected. The results indicated that reduced glutathione levels in liver and pancreatic tissue decreased, while protein carbonyl, advanced oxidized protein products and lipid peroxidation levels were elevated in diabetic group. Antioxidant enzyme activities decreased in liver tissues but increased in pancreatic tissues of the diabetic group. Administration of Mel, insulin or Mel + insulin reversed these biochemical changes in the diabetic animals. This work shows that in long-term oxidative stress conditions caused by STZ-induced diabetes, either Mel or Mel + insulin administration may improve the deteriorated oxidant/antioxidant system in both the liver and pancreas tissues. These results suggested that Mel alone or Mel + insulin treatments might have a significant role in protecting against liver and pancreatic damage in STZ diabetic rats via different antioxidant effects.