Liver DNA Fragmentation Research Articles

The ameliorating effect of Rutin on hepatotoxicity and inflammation induced by the daily administration of vortioxetine in rats

BackgroundVortioxetine (VORTX) is a potent and selective type of selective serotonin reuptake inhibitor (SSRI) that is mainly prescribed for treating major depression along with mood disorders as the first drug of choice. Limited previous findings have indicated evidence of liver injury and hepatotoxicity associated with daily VORTX treatment. Rutin (RUT), which is known for its antioxidant properties, has demonstrated several beneficial health actions, including hepatoprotection. Therefore the current study aimed to evaluate and assess the ameliorative effect of RUT against the hepatotoxic actions of daily low and high-dose VORTX administration.MethodsThe experimental design included six groups of rats, each divided equally. Control, rats exposed to RUT (25 mg/kg), rats exposed to VORTX (28 mg/kg), rats exposed to VORTX (28 mg/kg) + RUT (25 mg/kg), rats exposed to VORTX (80 mg/kg), and rats exposed to VORTX (80 mg/kg) + RUT (25 mg/kg). After 30 days from the daily exposure period, assessments were conducted for serum liver enzyme activities, hepatotoxicity biomarkers, liver antioxidant endogenous enzymes, DNA fragmentation, and histopathological studies of liver tissue.ResultsInterestingly, the risk of liver damage and hepatotoxicity related to VORTX was attenuated by the daily co-administration of RUT. Significant improvements were observed among all detected liver functions, oxidative stress, and inflammatory biomarkers including aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), albumin, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione S-transferase (GST), total protein, acid phosphatase, N-Acetyl-/β-glucosaminidase (β-NAG), β-Galactosidase (β-Gal), alpha-fetoprotein (AFP), caspase 3, and cytochrom-C along with histopathological studies, compared to the control and sole RUT group.ConclusionThus, RUT can be considered a potential and effective complementary therapy in preventing hepatotoxicity and liver injury induced by the daily or prolonged administration of VORTX.

In Vivo Anti-Hepatocellular Carcinoma Effects of the Chloroform Root Extract of Clausena excavata Burm.

Liver cancer is the most common cancer among males in Africa. The disease has a poor prognosis and its treatment is associated with toxicity and resistance. For this reason, numerous herbal combinations are being subjected to anticancer screening to circumvent the shortcomings of the conventional anticancer drugs. In the current study, the in vivo anti-cancer effects of the chloroform root extract of the herb, Clausena excavata Burm were investigated. Liver cancer was induced in mice by a single intraperitoneal injection of diethylnitrosamine (DEN) followed by oral administration of the promoter of carcinogenesis, 2-aminoacetyl fluorine that was mixed with the mice feed. The cytotoxicity of the root extract of C. excavata on liver cancer cells was investigated using liver enzyme, histology, DNA fragmentation and caspases assays. Real time qPCR was conducted to evaluate the effect of the extract on apoptotic genes. The findings revealed that the extract of C. excavata significantly decreased the progression of hepatocarcinogenesis and the toxicity-induced production of the liver enzymes, alanine and aspartate aminotransferases. The histological analyses of the liver tissues revealed evidence of apoptotic cell death. The extract also provoked significant (p < .05) expressions of caspase 9 protein and gene as well as other apoptotic genes (P53, P27, Apaf-1, cytochrome C, bax and bid). Therefore, we postulate that the chloroform root extract of C. excavata induces apoptosis of liver cancer in mice.

Antiapoptotic and anticoagulant effects of camel milk and camel urine in methotrexate-induced hepatotoxicity

ABSTRACT Methotrexate (MTX) is widely used chemotherapeutic and immune suppressant agent. Hepatotoxicity is a common side effect of chronic MTX therapy. This study investigated the hepatoprotective properties of camel milk (CM) and camel urine (CU) in hepatotoxicity induced by intraperitoneal injection of MTX 20 mg/kg. The MTX-intoxicated animals showed elevated serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, fasting blood glucose (FBG), liver DNA fragmentation marker (DFF-40), and serum and liver cytokeratin (CK-18), decreased serum proteins, albumin, fibrinogen, and total antioxidant capacity (TAC). Decreased antithrombin (AT) was associated with prolonged prothrombin time (PT) and activated partial thromboplastin time (APTT). Treatment with CM and CU for four weeks decreased the liver enzymes, FBG, DFF-40, and CK-18 levels and increased total proteins, albumin, fibrinogen, and TAC. However, the changes in AT, PT, and APTT persisted. CM and CU showed promising abilities to counteract MTX hepatotoxicity and they exerted cytoprotective, antiapoptotic, antioxidative, antihyperglycemic, and antithrombotic effects.

Hepatic Impact of Different Concentrations of Hibiscus rosa Zinc Oxide Nanoparticles on Rats.

Nanomaterial, especially zinc oxide nanoparticles, has entered the manufacture of many materials used in daily lives. The current study aimed to assess the impact of three concentrations of hibiscus rosa zinc oxide nanoparticles (HrZnONPs) and hibiscus rosa extract (Hre) on the liver tissue and DNA fragmentation of liver cells. A total of 35 adult male Wistar rats were grouped as follows: The first group which was the control (n=7) did not receive any treatment. The remaining 28 animals were randomly assigned to four groups. Group 1 (n=7) were subcutaneously injected with 100mg\kg BW of Hibiscus rosa extract for 60 days; the rats in group 2 were subcutaneouslyinjected with 25 mg\kg BW of HrZnONPs for 60 days; rats in group 3 were subcutaneouslyinjected with 75mg\kg BW of HrZnONPs for 60 days; rats in group 4 were subcutaneously injected with 100mg\kg BW of HrZnONPs for 60 days. The liver biomarkers, aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) have been assessed in serum at zero time, after one month, and after two months of the experiment. At the end of the experiment, all animals were euthanized, the liver was dissected, the specimen underwent a pathohistological investigation, and the percentage of DNA fragmentation was evaluated. The results pointed out that the rats which were treated with HrZnONPs at concentrations of 75 and 100 mg\kg B.W. demonstrated a salient elevation in serum AST, ALT, or ALP activity, a modulation in hepatic tissue architecture, and an elevated percentage of high DNA damage, as compared to those treated with HrZnONPs at a concentration of 25 mg\kg B.W. On the other hand, the recorded data indicated that the administration of Hre has some ameliorative effects on AST, ALP, and ALT levels, histological cross-section, and the value of comet assay for liver cells due to the role of Hre antioxidant. In conclusion, the results of the current study demonstrated that high doses of HrZnONPs had exerted more adverse effects, compared to low doses. Moreover, the findings confirmed the ameliorative impact of Hre on liver biomarkers, a histological cross-section of the liver, and DNA damage.

Assessment the Genotoxic Potential of Fluoxetine and Amitriptyline at Maximum Therapeutic Doses for Four-Week Treatment in Experimental Male Rats

Abstract &#x0D; At any moment, the continuous usage of medications can accompanied by DNA damage and the accumulation of such damages can cause serious consequences. Antidepressants are long-term used drugs and the incidence of their genotoxic impacts cannot be excluded. Therefore, this work was designed to investigate the possible genotoxic effects of the commonly used antidepressants (fluoxetine and amitriptyline) in adult male rats.&#x0D; Detection of DNA damage in individual cells was assessed by comet and micronucleus assays in three different cell populations i.e. liver, testis and bone marrow tissues of 24 swiss albino adult male rats. The animals were randomly allocated into three groups of 8 rats each: Group I - rats orally-administered distilled water via gavage tube for four weeks as a negative control. Group II - rats orally-treated with fluoxetine hydrochloride solution (7.2mg/kg/day) via gavage tube for four weeks. Group III - rats orally-treated with amitriptyline hydrochloride solution (27mg/kg/day) via gavage tube for four weeks.&#x0D; The results showed that both drugs (Group II and Group III) induced the same extent of DNA damage, as evidenced by a significantly higher DNA fragmentation in liver and testis tissues with increased frequencies of micronuclei formation in bone marrow tissues as compared with the negative control (Group I).&#x0D; These findings indicates that both Fluoxetine and Amitriptyline have genotoxic potentials and can induce the same extent of cytogenetic damage in rats. Special precautions and medical supervision should be taken in consideration with their uses.

Evaluation of Hepatoprotective Effect of a Polyherbal Megakutki against Paracetamol-Induced Hepatotoxicity

Background: Megakutki® (MK) is a polyherbal preparation of 11 standardized extracts that are individually proven for hepatoprotection scientifically. Aim: Study evaluated MK’s hepatoprotective potential against paracetamol (PCM) in in-vitro on Hep G2 cells using cell viability, cell cycle analysis and apoptotic studies and in in-vivo in Wistar rats using liver function tests, histological and DNA fragmentation study. Materials and Methods: In in-vitro studies, IC50 (50% inhibition in viability) values of silymarin, MK and PCM were found out by MTT assay. In-vitro hepatoprotection was found out by pretreating the cells with below-IC50 concentrations of MK and silymarin for 24h followed by PCM (at IC50 concentration) challenge for next 24h and % viability was evaluated using MTT assay. Same treatment protocol was followed for cell cycle analysis and apoptotic studies (100 and 200 µg/ml for MK and 50 µg/ml for silymarin and 40µM for PCM). In in-vivo study, animals were grouped in six, namely, vehicle, PCM control, silymarin (50 mg/kg, standard), MK (100 and 300 mg/kg) groups. Animals were dosed for 8 days while they were challenged on day 6 (except vehicle group) with PCM (2.75 g/kg p.o). On day 8, blood and livers were collected under anaesthesia and analyzed. Results: In-vitro results showed hepatoprotection by MK and silymarin by inhibition of PCM-induced cell death apoptotic cells percentage. In in-vivo study, MK and silymarin reversed the altered liver function and elevated oxidative stress markers (catalase, SOD, GSH, total thiols and lipid peroxidation) compared to paracetamol alone group. Both MK and silymarin decreased the percentage of DNA fragmentation and histopathological changes in liver tissue compared to the PCM group. Conclusion: The in-vitro and in-vivo studies showed the hepatoprotective effect of MK by the prevention of PCM-induced induction of oxidative stress by its antioxidant potential thereby preventing PCM-induced DNA damage.

The Efficacy of Royal Jelly in the Restoration of Liver Injury in Irradiated Rats

RADIATION therapy is associated with a risk of long-term adverse effects. Royal jelly (RJ), a natural product extracted from honey bees is rich in compounds with many biological activities. This study aims at evaluating the role of RJ against gamma-radiation induced liver injury. Twenty-four male albino rats were divided into four groups. Control, IRR: whole-body exposed to gamma radiation (3 Gy every 3 days up to 9 Gy), RJ: received RJ by gavages (250 mg/kg BW) during 15 days, RJ+IRR: received RJ before the 1st radiation fraction and the treatment continued for 14 days. Animals were sacrificed one day post the last RJ dose. The results revealed that RJ significantly reduced the radiation-induced increases in liver malondialdehyde MDA, protein carbonyl CO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), markers of lipid, protein and DNA oxidation, accompanied by significant elevations of glutathione content (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. A significant reduction in the elevation of liver DNA fragmentation and caspase-3 activity was also recorded. In the serum, the level of the inflammatory markers, tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) and the level of the fibrotic markers collagen IV and laminin were significantly lower than their corresponding values in irradiated rats. The amelioration in the extent of liver injury obtained by RJ treatment was substantiated by significant improvement of liver functions verified by lowering the activity levels of liver function enzymes. It could be concluded that RJ by suppressing oxidative stress and decreasing inflammatory, apoptotic and fibrotic markers may alleviate the progression of radiation-induced liver injury.

THERAPEUTIC POTENCY OF SWEET ORANGE JUICE OVER LIVER GENOTOXICITY INDUCED BY PESTICIDE LANNATE IN RATS

Objective: The aim of the present investigation was to study the potential effect of sweet orange juice against liver genotoxicity induced by lannate.&#x0D; Methods: adult 36 female rats were divided into 6 groups: group C (control group), group L (lannate group) injected intraperitoneal (i. p.) with 1 mg/kg b. wt. lannate for one day, group J (orange juice group) orally administered a dose of 0.1 ml/10 g b. wt. of orange juice for 48 h, group J+L received the orange juice prior to lannate, group J with L received lannate in continuous with the orange juice and group L+J received lannate prior to the orange juice. Tested parameters were DNA fragmentation, micronucleus, histopathology examination and biochemical analysis.&#x0D; Results: it was found that, the intake of lannate caused high DNA fragmentation and significant increase (P&lt;0.001) in the number of micronucleated polychromatic erythrocytes in the bone marrow. Furthermore, lannate exhibited some pathological changes in the liver tissues as well as a significant (P&lt;0.001) decrease in the total antioxidative capacity (TAC) and a significant increase in the total oxidative capacity (TOC). On the other hand, orange juice administration of all treatments (pre-treatment, continuous and post-treatment) gave some amelioration against liver damage induced by lannate. While the best results were evidenced in the continuous treatment group where the juice could attenuate liver DNA fragmentation and significantly decreased (P&lt;0.001) the number of micronucleated polychromatic erythrocytes. In addition, it improved the induced degenerative histopathological changes as well as ameliorated the changes occurred in TAC and TOC significantly (P&lt;0.001).&#x0D; Conclusion: the antigenotoxic impact of orange juice against lannate was therapeutic and hence can counteract the poisonous effect of the pesticide in people who exposed to it.

Detoxifying and antioxidant effect of ellagic acid nano particles in rats intoxicated with sodium nitrites

Sodium nitrite is used as a preservative in food products to stabilize color and reduce rancidity. Its absorption into the body causes many diseases. Ellagic acid is a natural polyphenol that contains powerful antioxidants, but it is taken as a poorly absorbed food. Therefore, chitosan-coated nanoparticles (EANP@CS) were loaded to enhance their bioactivity and bioavailability after oral administration. EANP@CS was administrated in rats given water containing sodium nitrite to reduce toxins. Ellagic acid was extracted from pomegranate and manufactured EANP@CS. EANP@CS was identified by FT-IR, UV, X-ray diffraction and TEM. Average EANP@CS size ranges from 20–62 nm. Rats were divided into five groups: normal, treated using EANP@CS; rats were receiving nitrite for 8 weeks, and the last two groups were treated with EANP@CS. Serum and liver NO, MDA, and DNA fragmentation were reduced. Liver thiol and GSH levels, and Gpx, catalase and GST activities increased in rats treated with EANP@CS rats compared to rats drinking nitrites. Liver NOS activity was reduced 7 and 4.9 times in rats treated with EANP@CS during or after discontinuation of nitrite administration, respectively. Liver arginase activity was raised in rats that drink nitrite or were treated using EANP@CS. Inflammatory infiltrations of the liver, kidney, and spleen were observed in the tissues of rats that received nitrites and improved when the rats were given EANP@CS. EANP@CS improved oral bioavailability and reduce the risk of sodium nitrite in rats. EANP@CS can be used as a therapeutic goal to detoxify any unwanted toxic substance in food.

Costus root aqueous extract modulates rat liver toxicity, DNA damage, injury, proliferation alterations induced by plant growth regulator Ethephon

Ethephon (Ethrel®) is an ethylene-based plant growth regulator that used in agriculture and it has direct and indirect effects on human health, direct effect via its inhalation during usage in agriculture and indirect effect through the diet (Fruits and vegetables) that is sprayed with it. The current study aimed to examine the possible modifying effects of costus (Saussurea lappa) root aqueous extract against Ethephon induced liver toxicity, injury, DNA fragmentation and PCNA alterations in male rats. Fifty adult male rats were divided into 5 groups (1st, control; 2nd, Costus; 3rd, Ethephon; 4th, Post treated Ethephon with costus; 5th, self-healing Ethephon). Current results revealed that; a significant increase in aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), liver injury, DNA damage and PCNA expressions in Ethephon group when compared with control group. In contrast; a significant decrease in albumin and total proteins in Ethephon group when compared with control group. Treatment of rats with costus after Ethephon improved these alterations as compared with Ethephon self-healing. So, it could be concluded that costus root extract worth to be considered as a natural substance for ameliorating the hepatic toxicity induced by plant growth regulator Ethephon.

Citicoline Ameliorates Neuro- and Genotoxicity Induced by Acute Malathion Intoxication in Rats

Objective: In the present study, we explored the therapeutic potential of citicoline in preventing malathion induced neurotoxicity and genotoxicity. Citicoline has been shown to act as a neuroprotective in experimental animal models of ischemia and other types of brain injuries. Methods: Acute malathion intoxication was induced by intraperitoneal injection of malathion (150 mg/Kg, once per day) for two successive days. Citicoline was co-administered in three doses (100, 200, 300 mg/kg, p.o.). Serum Butyrylcholine esterase (BChE) and Paraoxonase-1 (PON-1) were assessed as exposure biomarkers. Oxidative stress biomarkers were assessed in the different brain regions (cortex, striatum, and subcortex) in addition to TNF-α. Genotoxicity was tested by chromosomal aberrations, mitotic index, DNA fragmentation, and micronucleus tests. Results: Malathion administration resulted in marked suppression of serum BChE and PON-1 activities. Also, the exposure to the pesticide led to elevated malondialdehyde (MDA), nitric oxide (NO), and decreased reduced glutathione (GSH) levels in investigated brain regions in addition to elevated striatal tumor necrosis factor-α (TNF-α) level. Malathion also caused profound structural chromosomal aberrations, increased liver DNA fragmentation, and mitotic index. These effects were alleviated with the administration of citicoline dose-dependently. Conclusion: Our data indicate that citicoline can protect against malathion neurotoxic and genotoxic potential, possibly through antioxidant, anti-inflammatory activities, and restoring energy stores

Posttreatment Effects of Olea Europaea L. Leaf Extract on Carbon Tetrachloride-Induced Liver Injury and Oxidative Stress in Rats.

The aim of this study is to examine the therapeutic effects of Olea europaea L. leaf extract on carbon tetrachloride (CCl4)-induced liver damage in rats. In the experiments, 3- to 4-month-old 28 male Sprague-Dawley rats were divided into four groups: control, O. europaea leaf extract, CCl4, and curative. The CCl4 and curative groups received CCl4 (0.2 mL/kg) intraperitoneally for 10 days to form hepatic injury. O. europaea (80 mg/kg) leaf extract was given orally to the curative group dissolved in distilled water the following 14 days. Hepatic and antioxidant enzyme levels, p53, caspase 3, lipid peroxidation marker malondialdehyde (MDA), and also DNA fragmentation levels were determined to establish oxidative stress in hepatic cell damage and its consequences. After formation of liver damage, oral administration of the O. europaea significantly reduced CCl4-induced elevations of serum alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase levels (P < .001), MDA levels of both blood (P < .001) and liver tissues (P < .001), DNA fragmentation (P < .001), p53 (P < .001), and caspase 3 (P < .001) levels of liver tissues. Also this administration in curative group significantly increased CCl4-induced reductions of superoxide dismutase (SOD) (P < .001) and catalase (CAT) (P < .001) activity of blood samples and decreased SOD (P < .001) and CAT (P < .05) activity observed in liver tissue curative groups compared with CCl4 curative group. In CCl4 group, liver tissue samples exhibited remarkable damage because of CCl4 and reduction of these damages were observed in the curative group. Our results showed that O. europaea leaf extract was effective in reducing hepatic damage caused by CCl4 by reducing lipid peroxidation, regulating antioxidant enzymes, and minimizing DNA damage.

Haematological and Genotoxicity Evaluations of Phytochemical Compounds from n-Hexane Extract of Uvaria chamae Stem on Selected Organs in Mice

Abstract Phytochemical constituents of plants extracts have been well investigated as leads for drug discovery and development. However, aside their immense medicinal properties, their safety is also of paramount importance, therefore evaluating the toxicity of plants extracts and their phytochemicals is an important aspect of quality measures to meet the requirements for consumption.This study was done to identify the volatile phytochemical compounds present in n-hexane extract of Uvaria chamae stems (UCSH) with the aid of gas chromatography-mass spectrometry (GC-MS) and to evaluate the effects of this non-polar extract on DNA using diphenylamine (DPA) and agarose gel electrophoresis assays, also to investigate the haematological parameters using an auto Haematology Analyzer.The GC-MS analysis of UCSH identified some compounds which include; squalene, lupeol, stigmasterol, β-sitosterol, and Benzyl benzoate with excellent medicinal properties. Genotoxicity assays results showed significant reductions in DNA fragmentation in liver and testis cells of mice as against the DNA biomarker and vehicle control group. Haematological results showed significant increase in white blood cells (WBC), red blood cell (RBC), platelets (PLT) and lymphocytes (LYMP) but significant reduction in mean corpuscular - volume (MCV), haemoglobin (MCH), and haemoglobin concentration (MCHC).The present study showed that the phytochemicals present in the n-Hexane extract of Uvaria chamae stems may play protective role in the genomic DNA of liver and testis tissues and also may induce hematological changes which may enhance the immune system.

The role of molecular modelling strategies in validating the effects of chrysin on sodium arsenite-induced chromosomal and DNA damage.

Chrysin (CHR) is a food-based bioactive ingredient whereas, sodium arsenite (SA) is one of the major contaminant in drinking water. When ingested, SA contributes to tissue damage due to bioactivation by S-adenosyl methionine (SAM)-dependent methyltransferase. Hence, the needs to nullify this effect by investigating the potentials of CHR on SA-induced genotoxicity in rats. The experiment was divided into two successive stages (ameliorative and preventive, curative studies) for 1 week. Rats were divided into four groups: distilled water, 10mg/kg SA, 10mg/kg CHR and co-administration. In stage 2, the experimental groups were given either CHR or SA for 1 week, and treated in reversed order for additional week. Lipid peroxidation, protein carbonyl and DNA fragmentation in liver, blood brain and bone marrow cells micronucleus were assayed for using standard protocols. Molecular docking of SAM-dependent methyltransferase in the presence of CHR was conducted. CHR significantly ( p < 0.05) decreased the level of lipid peroxidation, protein carbonyls and DNA fragmentation in blood, liver and brain tissues as against group treated with SA. It also significantly ( p<0.05) reduced the level of micronuclei generated in bone marrow cells. The effects of CHR were shown to be ameliorative, preventive and curative in nature. Furthermore, CHR was able to dock (with binding energy of -24.81 kcal/mol and predicted inhibition kinetic constant (Ki) of 0.959 µM) into the active site of SAM-dependent methyltransferase with strong hydrogen bond and hydrophobic interactions. The study might have unravelled the potentials of CHR against SA-induced chromosomal and DNA damage, which might be due to inhibition of SAM-dependent methyltransferase.

Grape Seed Extract Alone or Combined with Atropine in Treatment of Malathion Induced Neuro- and Genotoxicity

The aim of this study was to investigate the effect of treatment with grape seed extract (GSE) on the neurotoxic and genotoxic effects of acute malathion exposure. Rats received malathion (150 mg/kg by i.p. injection) for two successive days alone or combined with GSE at doses of 150 or 300 mg/kg, orally or with GSE at 300 mg/kg and atropine at a dose of 2 mg/kg, i.p. Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, paraoxonase (PON1) were determined in cortex, striatum, and rest of brain tissue (subcortex). Interleukin-1β (IL-1β), and butyrylcholinesterase (BChE) activities were determined in brain regions. Cytogenetic analyses for chromosomal aberrations in somatic and germ cells, micronucleus test, Comet assay, DNA fragmentation of liver cells and histopathological examination of brain and liver sections were also performed. Malathion resulted in an increase in MDA, nitric oxide; a decrease in GSH and PON1 activity in different brain regions. IL-1β increased, while BChE activity decreased in brain after the administration of malathion. The insecticide also caused marked structural and numerical chromosomal aberrations and increased liver DNA fragmentation. The Comet assay showed a significant increase in DNA damage of peripheral blood lymphocytes. These effects of malathion were alleviated with the administration of GSE alone or combined with atropine. Addition of atropine to treatment with GSE was associated with significant decrease in MDA, BChE and chromosomal aberrations compared with GSE only treatment. Our data indicate that GSE protects against malathion neurotoxic and genotoxic effects, most likely through reducing brain oxidative stress and inflammatory response.

Modulatory effects of green tea extract against the hepatotoxic effects of 4-nonylphenol in catfish (Clarias gariepinus)

The antioxidant role of the green tea (Camellia sinensis) extract (GTE) was examined to remedy the toxic effects of (0.2mgl−1) 4-nonylphenol(4-NP). Biochemical parameters, antioxidant enzymes, liver lipid peroxidation (LPO), DNA fragmentation, and apoptosis as well as histopathology of liver of African catfish Clarias gariepinus were considered. Catfishes were divided into four groups: first group (control), second group (0.2mgl−1 of 4-NP), third group (0.2mgl−1of 4-NP +100mg GTE l−1water), and fourth group (0.2mgl−1 of 4-NP +200mg GTE l−1water). The results showed that significant increments of serum glucose, AST, ALT, total protein, total lipids, cholesterol, G6PDH, and cortisol. Meanwhile, serum acetylcholinesterase, ALP, and LDH were significantly reduced. In addition, antioxidant enzymes (SOD, CAT, GST, and TAC) levels were reduced in 4-NP treated fish compared to control. Also, there were significant increments in hepatic LPO, DNA fragmentation, and apoptotic erythrocytes in 4-NP treated fish compared to control. Liver of 4-NP treated fish showed some histopathological alterations such as, vacuolization in hepatocytes, congestion in central vein, infiltration of mononuclear inflammatory cells, and necrosis as well as depletion of glycogen content of liver. Addition of green tea extract into the water restored the alterations in most of those biomarkers induced by 4-NP. We concluded that, GTE has a protective role against hepatic failure, depletion of antioxidant defense, and genotoxicity induced 4-NP in C. gariepinus.

Amelioration of thioacetamide-induced liver toxicity in Wistar rats by rutin.

This study was designed to evaluate the effect of rutin on hepatotoxicity induced by thioacetamide (TAA) in rats. Four groups of male Wistar rats consisting of six rats each were used: Group I: control group; Group II: rats receiving single injection of 300 mg kg−1 body weight of TAA intraperitoneally; Group III: rats administered rutin (10 mg kg−1 body weight) dissolved in saline orally for 2 weeks; and Group IV: rats administered rutin (10 mg kg−1 body weight) dissolved in saline orally for 2 weeks followed by TAA injection last day of second week. All groups were sacrificed after 24 h of treatment and hepatic toxicity was analyzed with respect to liver toxicity markers, liver DNA fragmentation, and histology of liver tissue. Administration of TAA in Wistar rats resulted in significant increase of hepatic markers, DNA fragmentation in the hepatocytes, and changes in histology. Pretreatment of rats with rutin before 2 weeks of TAA assault resulted in the complete reversal of TAA-mediated hepatic toxicity (P < 0.0001 to P < 0.01) with concomitant restoration of DNA fragmentation. This study suggests rutin as a protective agent for restoration of toxicity caused by TAA.

Evaluation of Genotoxic and Hepatotoxic Effects of Graphene Oxide Nanosheets in Male Albino Mice.

Graphene oxide Nano-sheets (GOs) have a wide range of industrial, biochemical and medical applications regarding their unique physical, chemical and biocompatibility properties. For assessment of toxicological potential of graphene oxide nanosheets ninety male mice were divided into six groups; the control and five treated groups: animals of the control group received an intraperitoneal (i.p) injection of 0.2 ml saline solution (0.9% NaCl) once weekly for eight weeks. The treated groups were received an i.p injection of 10, 50, 100, 250, and 500 µg GOs/kg body weight once weekly, for eight weeks. Animals of all groups were sacrificed after 7, 28, and 56-days post treatment. The present study was conducted to evaluate the genotoxic effects of GOs on mice liver cells using alkali comet assay. In addition, physiological investigations and description of hepatic histopathological alternations were carried out. Results revealed that GOs induced DNA damage (DNA fragmentation), represented in dose and time-dependent increase in % tail DNA migration, tail moment and comet tail length. As well as, a diminish in % head DNA in nuclei of liver of GOs-treated mice versus control groups. The effect of GOs on hepatic superoxide dismutase (SOD), catalase (CAT) activities and glutathione (GSH) level indicated slight decrease at low doses (10 and 50 µg) at all time intervals of experimental period as compared to the control groups. The administration of high doses of GOs (100, 250, and 500 µg) indicated a significant diminish in SOD, CAT activities and decrease in GSH level; with subsequent elevation in malondialdehyde (MDA) levels in liver as compared to control groups. Various hepatic histopathological alternations were dose and time dependent in GO-treated mice versus control. In conclusion, the induction of DNA fragmentation in liver denoting the genotoxicity of GOs in dose and time dependent manner. GOs had the ability for inducing various hepatic alternations in a dose and time dependent manner indicating cytotoxicity presumably by oxidative stress. Thus, GOs should be used under strict control and these serious side effects should be taken into consideration when used in vivo treatments.

Antidyslipidemic, Anti-Inflammatory, and Antioxidant Activities of Aqueous Leaf Extract of Dioscoreophyllum cumminsii (Stapf) Diels in High-Fat Diet-Fed Rats.

Dioscoreophyllum cumminsii (Stapf) Diels leaves are widely used in the treatment of diabetes, obesity, and cardiovascular related complications in Nigeria. This study investigates the anti-inflammatory and antiobesity effect of aqueous extract of Dioscoreophyllum cumminsii leaves in high-fat diet- (HFD-) induced obese rats. HFD-fed rats were given 100, 200, and 400 mgkg−1 body weight of aqueous extract of Dioscoreophyllum cumminsii leaves for 4 weeks starting from 9th week of HFD treatment. D. cumminsii leaves aqueous extract reversed HFD-mediated decrease in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose 6-phosphate dehydrogenase. Moreover, HFD-mediated elevation in the levels of conjugated dienes, lipid hydroperoxides, malondialdehyde, protein carbonyl, and DNA fragmentation in rats liver was lowered. HFD-mediated alterations in serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol were significantly reversed by the extract. The treatment of HFD-fed rats reduced the levels of insulin, leptin, protein carbonyl, fragmented DNA, and tumour necrosis factor-α and interleukin- (IL-) 6 and IL- 8 and increased the adiponectin level. This study showed that aqueous extract of Dioscoreophyllum cumminsii leaves has potential antiobesity and anti-inflammatory effects through modulation of obesity-induced inflammation, oxidative stress, and obesity-related disorder in HFD-induced obese rats.

Hepato- and neuro-protective influences of biopropolis on thioacetamide-induced acute hepatic encephalopathy in rats.

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato- and neuro-protective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into 5 groups: Group 1 (normal control) received only saline and paraffin oil. Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4, and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of HE were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato- and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, biopropolis, at a dose of 200 mg/kg per day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.