Cell Damage In Rats Research Articles

Melittin protects against neural cell damage in rats following ischemic stroke

ObjectiveIn this study, we explored the neuroprotective effect of melittin (MEL) after brain ischemia using a rat model. MethodsThe rats underwent middle cerebral artery occlusion (MCAO) for 60 min and were randomly divided into the control group, saline group, and MEL group. Rats in each group were injected intraperitoneally with MEL one day before MCAO until sacrificed. Morris water maze and rotation test were used to assess locomotor function and cognitive ability. The 9.4 Tesla MRI was used to scan and assess the infarct volume of the rat brains. Immunohistochemistry was used to detect the sites of action of MEL on microglia. Western blot and ELISA were used to measure the effect of MEL on the production of pro-inflammatory cytokines. The effect of MEL on neuronal cell apoptosis was observed by flow cytometry. ResultsCompared with the saline group, MEL treatment significantly increased the density of neurons in the cerebral cortical and reduced the cerebral infarct size after MCAO (33.9 ± 8.8% vs. 15.8 ± 3.9%, P < 0.05). Meanwhile, the time for MEL-treated rats to complete the water maze task on the 11th day after MCAO was significantly shorter than that of rats in the saline group (P < 0.05). MEL treatment also prolonged the rotarod retention time on day 14 after MCAO. Immunohistochemistry analysis showed that MEL inhibited the activation of microglia and suppressed the expression of TNF-α, IL-6, and IL-1β in the brain after ischemia. MEL treatment resulted in a significant decrease in TLR4, MyD88, and NF-κB p65 levels in extracts from the ischemic cerebral cortex. Finally, MEL reduced neuronal apoptosis induced by ischemic stroke (P < 0.05). ConclusionMEL treatment promotes neurological function recovery after cerebral ischemia in rats. These effects are potentially mediated through anti-inflammatory and anti-apoptotic mechanisms.

TLR4 Inhibition Protects against Retinal Ganglion Cell Damage in Rats with Chronic Ocular Hypertension.

This study aims to investigate the protective effect of Toll-like receptor 4 (TLR4) inhibitor Resatorvid (TAK-242) on retinal ganglion cells (RGCs) in a chronic ocular hypertension (COH) rat model, as well as to explore the potential involved mechanisms. COH model was built up in rats with a single intracameral administration of cross-linking hydrogel. The expression levels of TLR4, NLR family pyrin domain containing 3 (NLRP3), microglial activation and pro-inflammatory cytokines were evaluated in COH retinas and COH retinas treated with TAK-242 using immunofluorescence staining and Western blot. Additionally, retrograde labeling and neuronal nuclear protein (NeuN) staining were performed to count RGCs. Activated microglia and increased TLR4 expression were observed in the retinas of COH rats. This was accompanied by upregulated expressions of NLRP3, tumor necrosis factor alpha (TNF-α), cytokine interleukin-1β (IL-1β) and Interleukin-6 (IL-6). Intravitreal injection of TAK-242 promoted the survival of RGCs by attenuating microglial activation, interfering with the TLR4-NLRP3 pathway and regulating pro-inflammatory cytokines. Targeting TLR4 inhibition could be a potential therapeutic strategy to protect RGCs from COH damage.

Coenzyme Q10 nanoparticles prevents monocrotophos exposure mediated neurotoxicity by attenuating the histological alterations in rats

Organophosphate (OP) insecticide monocrotophos (MCP) is extremely hazardous to all living beings. This study shows that coenzyme Q10 nanoparticles (CoQ10NPs) can protect rats from the neurotoxicity caused by MCP-induced oxidative stress. In this study, male albino rats were divided into six groups i.e. control, CoQ10NPs low dose (50mg/kg b. wt) treated group, CoQ10NPs high dose (100mg/kg b. wt) treated group, MCP (4.5mg/kg b. wt) exposed group, CoQ10NPs low dose + MCP (50mg and 4.5mg/kg b. wt) treated group and CoQ10NPs high dose + MCP (100mg and 4.5mg/kg b. wt) treated group. The observation showed the depletion in the level of AChE activity and elevation in the levels of protein oxidation and lipid peroxidation which indicated the emerging of oxidative stress resulting in the induction of neurotoxicity. A significant decrease in the level of various enzymatic and non-enzymatic antioxidants like glutathione (GSH), catalase and superoxide dismutase (SOD) was observed in rat brain. The histopathological study indicated the major structural alterations in neuronal tissues of rats. These additionally backed up the induction of toxic effects caused by MCP exposure in rats. The prior co-treatment of CoQ10NPs along with MCP exposure depicted the significant protection from the oxidative stress generation and improved the structural and histological alteration in the rat brain. Hence, it can be concluded that CoQ10NPs have the strong therapeutic potential to reduce the MCP-induced oxidative stress, indicating their protective effects against MCP-induced neuronal cell damage in rats.

Green tea extract modulates lithium-induced thyroid follicular cell damage in rats.

The aim of the current work was to clarify the modulation role of green tea extract (GTE) over structural and functional affection of the thyroid gland after long term use of lithium carbonate (LC). The suggested underlying mechanisms participating in thyroid affection were researched. Twenty-four Sprague-Dawley adult albino rats were included in the work. They were divided into three groups (control, LC, and concomitant LC + GTE). The work was sustained for 8 weeks. Biochemical assays were performed (thyroid hormone profile, interleukin 6 [Il-6]). Histological, histochemical (Periodic Acid Schiff [PAS]) and immunohistochemical (caspase-3, tumour necrosis factor alpha [TNF-α], proliferating cell nuclear antigen [PCNA]) evaluations were done. Oxidative/antioxidative markers (malondialdehyde [MDA]/gluthathione [GSH], superoxide dismutase [SOD]) and Western blot evaluation of the Bcl2 family were done. Lithium carbonate induced hypothyroidism (decreased T3, T4/increased thyroid-stimulating hormone [TSH]). The follicles were distended, others were involuted. Some follicles were disorganised, others showed detached follicular cells. Apoptotic follicular cells were shown (BAX and caspase-3 increased, Bcl2 decreased, BAX/Bcl2 ratio increased). The collagen fibres' content and proinflammatory markers (TNF-α and IL-6) increased. The proliferative nuclear activity was supported by increased expression of PCNA. Oxidative stress was established (increased MDA/decreased GSH, SOD). With the use of GTE, the thyroid hormone levels increased, while the TSH level decreased. Apoptosis was improved as BAX decreased, Bcl2 increased, and BAX/Bcl2 ratio was normal. The collagen fibres' content and proinflammatory markers (TNF-α and IL-6) decreased. The expression of PCNA and caspase-3 were comparable to the control group. The oxidative markers were improved (decreased MDA/increased GSH, SOD). In conclusion, prolonged use of LC results in hypothyroidism, which is accompanied by structural thyroid damage. LC induced thyroid damage through oxidative stress that prompted sterile inflammation and apoptosis. With the use of GTE, the thyroid gland regained its structure and function. The protecting role of GTE is through antioxidant, antifibrotic, anti-inflammatory, and antiproliferative effects.

Kersen (Muntingia calabura L.) Ethanol Extract Repairs Pancreatic Cell Damage, Total Coliforms, and Lactic Acid Bacteria in Hyperglycemic Mice

Hyperglycemia is a condition in which the blood glucose levels exceed normal limits. Ethanol extract of Jamaican cherry leaves (Muntingia calabura L.) contains active components that have the potential to lower blood sugar levels and heal pancreatic cell damage in rats. Gut microbiota imbalance can cause immune system abnormalities, illnesses, and metabolic disorders, including diabetes. The aim of the present study was to determine whether an ethanol extract of Jamaican cherry leaves can repair pancreatic cell damage, as well as influence the total coliforms and lactic acid bacteria in hyperglycemic mice. In this study, 25 mice were randomly placed into five groups, which were then provided with food and drinking water. Alloxan in a dose of 160 mg/kg bw was administered to the positive control group and three treatment groups. Each of the three groups was then treated with the ethanol extract of Jamaican cherry leaves at doses of 300, 400, or 500 mg/kg bw for 14 days. The groups that received the extract were able to repair the pancreatic damage considerably by increasing the number of normal pancreatic cells. This was supported by histological observations. The total abundance of lactic acid bacteria in hyperglycemic mice was 1.08 ± 45 x 1010 CFU/g, which was substantially lower than that in mice treated with the extract. The overall coliform abundance in hyperglycemic mice was 4.37 ± 41 x 1010 CFU/g, which was higher than that in mice supplemented with the extract. Therefore, the administration of Jamaican cherry leaf ethanol extract on a regular basis can increase the abundance of cecum microbiota in hyperglycemic mice. Furthermore, this extract can be used as a natural alternative treatment for recovering pancreatic cell damage.

Effects of a combination of Sauropus androgynus L. leaf and Zingiber Ottensii rhizome on fatty acid profile and liver damage in rats

Background: High fat and carbohydrate diets may lead to the malfunction of hepatic cells because of excessive lipolysis of fat tissues and the subsequent increase of free fatty acids in the liver. This is characterised by histological changes in the hepatic cells which then undergo necrosis. High fat and carbohydrate diets may also lead to gut microbiota dysbiosis. Objectives: This study aims to determine the effect of the combination of katuk leaf and black bangle rhizome on the short chain fatty acid (SCFA) profile and liver cell damage in rats induced by a high fat and carbohydrate diet. Methods: The research method used is a preventive experimental study in vivo. Four groups of test animals were distinguished into negative group, positive group, comparative group, and 15% combination test group, which was carried out for 21 days. Examined parameters were: SGPT (Serum Glutamic Pyruvic Transaminase), SGOT (Serum Glutamic Oxaloacetic Transaminase), Triglyceride, and hepatic cells histopathology. The results were examined by SPSS and showed a significant difference (p &lt; 0.05). Results: Parameter results showed the reduction of SGOT in the combination test group. The combination of katuk leaf and black bangle rhizome can increase acetic acid and lower the Manja Roenigk score, and it is possible to inhibit liver cell damage. Conclusion: The combination of katuk leaf (Sauropusxandrogynus L.Merr) and black bangle rhizome (Zingiber ottensii Val) may affect the SCFA levels and help lower the risk of liver cell damage.

EFFECT OF NIGELLA SATIVA EXTRACTS IN LIVER CELL OF RATTUS NORVEGICUS INDUCED BY PIROXICAM

Piroxicam has the potential to cause side effects, especially in the liver, so that it can causes cell damage and impair the function and work of the liver organs. One way to minimize liver cell damage is by giving black cumin (Nigella sativa). This study aims to analyze the effect of black cumin (Nigella sativa) extract on the level of liver cell damage in rats (Rattus norvegicus) induced by Piroxicam. This study used 80 male rats and divided into 3 groups, namely negative control (K-), Piroxicam non-extract (P-) and Piroxicam plus extract (P +). Black cumin extract is given orally at a dose of 2 gr/kgBW; 3 gr/kgBW; 4 gr/kgBW; 5 gr/kgBW and 6 gr/kgBW, while the Piroxicam dosage given is 1 g/kgBW and 3 g/kgBW. The liver cell damage was done by observing the microscopic image. The results showed that the more doses of Piroxicam were given, the higher the level of cell damage. Along with increasing the dose of black cumin extract, the cell damage is reduced.

Protective effect of vitamin E on nickel sulfate-induced renal dysfunction in rats

Introduction: The kidney is a major organ for nickel induced toxicity. Objectives: The purpose of this investigation was to determine the protective impact of vitamin E on nickel sulfate (NiSO4 ) caused kidney dysfunction in rats using biochemical and histopathological approaches. Materials and Methods: Adult male Wistar rats were selected as animal models and randomly divided into four groups (five rats in each group) as follows; group 1. The animals received orally (gavage) 250 mg/kg vitamin E (dissolved in corn oil) 30 minutes before inhalation exposure to1mg NiSO4 /m3 . This experiment was performed for 6 hours daily for 10 consecutive days. Group 2; the rats received by gavage corn oil (vehicle) 30 minutes before inhalation exposure to1mg NiSO4 /m3 . This experiment was performed for 6 hours daily for 10 consecutive days. Group 3; animals of this group were given by gavage 250 mg/kg vitamin E only (without exposure to NiSO4 ) for 10 consecutive days. Group fourth were received by gavage an equal volume of vehicle (corn oil) for 10 consecutive days. All animals were killed 24 hours after the last treatments with sodium pentobarbital. Kidney tissues were removed. One part of the tissues were used for glutathione (GSH) and malondialdehyde (MDA) determination, other parts were fixed and processed for light microscopy. Results: The levels of MDA significantly increased and GSH decreased in rats exposed to NiSO4 in comparison to those in non-exposed rats. Histopathological observations also indicated that NiSO4 induced damage in the kidney. Additionally, administration of vitamin E prior to exposure to NiSO4 markedly decreased renal damage-induced by NiSO4 . Conclusion: The study showed that respiratory inhalation of NiSO4 induced oxidative stress and caused cell damage in rats’ kidney. Vitamin E effectively alleviated Ni-induced nephrotoxicity in rats. These observations suggest that vitamin E may have a protective effect against Ni-induced oxidative stress in the rats’ kidney.

The liver sinusoidal endothelial cell damage in rats caused by heatstroke

This study was designed to explore whether liver sinusoidal endothelial cells (SECs) play a pathological role in liver injury of heatstroke (HS) in rats. An HS rat model was prepared in a pre-warmed incubator. Rats were randomized into four groups: HS-sham group (SHAM group), the 39°C group, the 42°C group, and the HS group. The serum concentrations of SEC injury biomarkers including hyaluronic acid (HA), von Willebrand factor (vWF), thrombomodulin (TM), were measured. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and endothelium-derived vasoactive substances including endothelin-1 (ET-1) and nitric oxide (NO) were determined using a commercially available kit. Hepatic tissues were obtained for histopathological examination, electron microscopy examination, immunohistochemistry, and reverse transcription polymerase chain reaction (PCR) analysis. Our study team found increased levels of plasma ALT/AST during the course of HS. We were also able to detect microcirculation changes and inflammatory injury of the liver (especially in the sinusoidal areas). In addition, markers of SEC injury were significantly elevated. Thrombosis-related markers including vWF and TF expression levels were significantly upregulated and TM levels downregulated. Furthermore, imbalance between ET-1 and NO levels were detected. In conclusion, damage of SECs could result in microcirculation disturbances and pro-inflammatory injury in the liver during HS, which could prove to be a potential pathogenic mechanism of liver injury in HS.

Efficiacy of resveratrol and quercetin after experimental spinal cord injury.

The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury. In this experimental study, 42 male Sprague-Dawley rats were used. Spinal cord injury was performed with clip compression method at level of T4-5. The study was conducted using 6 groups: control, trauma, trauma and solvent, trauma and resveratrol, trauma and quercetin, and trauma with combined resveratrol and quercetin. All rats were euthanized 48 hours after the procedure. Effects of resveratrol and quercetin on serum and tissue total antioxidant capacity and paraoxanase activity level were examined. Compared to trauma group, there was a significant increase in total antioxidant capacity and paraoxanase activity level in resveratrol, quercetin, and combined treatment groups. There was no significant difference between resveratrol and quercetin groups with regard to total antioxidant capacity and paraoxanase activity level. Total antioxidant capacity and paraoxanase activity level were significantly higher in solvent group than trauma group. In histopathological evaluation, there was a decrease in polymorphonuclear leukocyte infiltration in solvent, resveratrol, quercetin, and combined treatment groups. Biochemical and histological staining results of present study showed that resveratrol and quercetin may be effective in preventing secondary damage in spinal cord injury.

Solanumnigrum L. as a Hepatoprotective Agent

Background : Liver damage may be caused by various factors. SolanumnigrumL.fruit is known to contain flavonoid antioxidant which is responsible for its hepatoprotective effect. A study was conducted to determine the protective effect of Solanumnigrum L. fruit infusion (SNFI) on CCl4-induced hepatic cell damage in rats. Methods : A complete randomized experimental study was conducted on 25 male Wistar strain-white rats (Rattusnorvegicus) which were divided into five groups during the period of September– October 2012. Group I (negative control) was given standardized food and water; group II (positive control) was induced by carbon tetrachloride (CCl4) 10% paraffin intraperitoneally by 8 mL/kg body weight on the 8th day of the study; group III, IV, V (treated) were given Solanumnigrum L. fruit infusion (SNFI) by 22.5g/100mL, 45 g/100mL and 90g/100mL concentrations for 8 days, respectively, prior to CCl4 induction. The calculation of necrotic liver cells was performed in 48 hours after induction. Data were statistically analyzed using Kruskal-Wallis test followed by Mann-Whitney post-hoc test. Results : The percentage of necrosis liver cells in group III, IV, and V was smaller compared to the positive control group. The protective effect of SNFI against CCl4-induced hepatotoxicity may be related to its ability to elevate the antioxidant agent in the body. There were significant differences in necrotic between Group II and group III, IV, V which were treated with SNFI. Conclusion : Further investigation is required to characterize the active ingredients and the mechanism of SNF action to confirm the hepatoprotective and antioxidant effects. Keywords : CCl4, hepatoprotective, Solanumnigrum L. DOI : 10.15850/amj.v2n1.433

Tacrolimus reversibly reduces insulin secretion, induces insulin resistance, and causes islet cell damage in rats.

To investigate the diabetogenic effects of the immunosuppressive agent tacrolimus, the reversibility of these effects upon treatment discontinuation, and the underlying mechanisms in a rat model. 60 healthy male rats were randomly divided into three groups for intragastric administration of tacrolimus either at 4 mg/kg/d or 2 mg/kg/d or an equal volume of normal saline (control). The treatment was administered for 5 months, followed by a 5-month period of no intervention. Fasting plasma glucose and insulin levels were used to calculate the homeostasis model assessment of ß-cell function (HOMA-ß) and insulin sensitivity index (ISI). Tacrolimus treatment significantly increased blood glucose concentrations (p < 0.05) and lowered HOMA-ß and ISI (p < 0.01) in a time- and dose-dependent manner. Five months after tacrolimus treatment, significant islet cell injury was observed. However, 5 months after tacrolimus discontinuation, blood glucose concentrations significantly declined, HOMA-β and ISI levels significantly increased, and islet cell morphology noticeably improved. In conclusion, tacrolimus treatment of healthy rats increased blood glucose concentrations in a time- and concentration-dependent manner. Development of tacrolimus-induced diabetes and reversibility after tacrolimus discontinuation may involve factors of and interactions between the insulin secretion pathway, local and/or systemic insulin resistance, and islet cell damage.

Change in kidney damage biomarkers after 13weeks of exposing rats to the complex of Paecilomyces sinclairii and its host Bombyx mori larvae

Complex of Paecilomyces sinclairii and host larvae, Bombyx mori, is a well known health food; however, concerns about nephrotoxicity have been raised. Kidney toxicity was investigated after 13 weeks of administering the complex orally to rats with parameters including blood urea nitrogen (BUN), creatinine, and kidney damage biomarkers, beta-2-microglobulin (β2m), glutathione S-transferase alpha (GST-α), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin. Dose-dependent kidney cell karyomegaly and tubular hypertrophy were observed, with higher severity in males. There was a dose-dependent increase in KIM-1 and TIMP-1 levels in kidney and urinary KIM-1, cystatin C, β2m, and osteopontin levels. KIM-1 and TIMP-1 increased in male kidneys had not recovered by 2 weeks after stopping exposure. Cystatin C in kidney was significantly lowered in all treatment groups at 13 weeks of administration. All the changes were more noticeable in males. These data indicate that the complex damage renal tubule cells with histopathological lesions and changes in biomarker levels. Kidney and urinary KIM-1 and cystatin C were the most markedly affected and early increased indicators among biomarkers tested, whereas BUN and creatinine were not affected.

Efficacy of a novel chelator BPCBG for removing uranium and protecting against uranium-induced renal cell damage in rats and HK-2 cells

Chelation therapy is a known effective method to increase the excretion of U(VI) from the body. Until now, no any uranium chelator has been approved for emergency medical use worldwide. The present study aimed to evaluate the efficacy of new ligand BPCBG containing two catechol groups and two aminocarboxylic acid groups in decorporation of U(VI) and protection against acute U(VI) nephrotoxicity in rats, and further explored the detoxification mechanism of BPCBG for U(VI)-induced nephrotoxicity in HK-2 cells with comparison to DTPA-CaNa3. Chelating agents were administered at various times before or after injections of U(VI) in rats. The U(VI) levels in urine, kidneys and femurs were measured 24h after U(VI) injections. Histopathological changes in the kidney and serum urea and creatinine and urine protein were examined. After treatment of U(VI)-exposed HK-2 cells with chelating agent, the intracellular U(VI) contents, formation of micronuclei, lactate dehydrogenase (LDH) activity and production of reactive oxygen species (ROS) were assessed. It was found that prompt, advanced or delayed injections of BPCBG effectively increased 24h-urinary U(VI) excretion and decreased the levels of U(VI) in kidney and bone. Meanwhile, BPCBG injection obviously reduced the severity of the U(VI)-induced histological alterations in the kidney, which was in parallel with the amelioration noted in serum indicators, urea and creatinine, and urine protein of U(VI) nephrotoxicity. In U(VI)-exposed HK-2 cells, immediate and delayed treatment with BPCBG significantly decreased the formation of micronuclei and LDH release by inhibiting the cellular U(VI) intake, promoting the intracellular U(VI) release and inhibiting the production of intracellular ROS. Our data suggest that BPCBG is a novel bi-functional U(VI) decorporation agent with a better efficacy than DTPA-CaNa3.

Beneficial effects of chlorogenic acid on methotrexate-induced cerebellar Purkinje cell damage in rats

Several studies have well confirmed the contribution of oxidative stress in the pathogenesis of methotrexate (MTX)-induced damage in the various organs. Many agents have been tested experimentally to reduce or inhibit the oxidative stress. The aim of this study was to determine the possible protective effect of chlorogenic acid (CLG) on MTX-induced cerebellar damage in rats.The rats were randomly divided into three groups as follows: I: control group; II: MTX group; III: CLG+MTX group.In the MTX group; malondialdehyde (MDA) content was found to be increased, whereas superoxide dismutase (SOD), catalase (CAT) activities, and glutathione (GSH) content were decreased. On the other hand, CLG markedly attenuated the elevated MDA content and prevented the deleterious effects of MTX on oxidative stress markers. MTX caused severe loss of Purkinje cells and apoptotic cell death in the cerebellum. The CLG administration before MTX treatment significantly reduced Purkinje cell damage and the expression of apoptotic cells.In conclusion, our results demonstrate that chlorogenic acid treatment may protect the impairment of oxidative stress and ameliorate MTX-induced cerebellar damage at biochemical and histological levels.

A New Hepatoprotective Flavone Glycoside from the Flowers of Onopordum alexandrinum Growing in Egypt

A bioactivity-guided fractionation of the ethyl acetate fraction of the flowers of Onopordum alexandrinum L. (Asteraceae) yielded a new flavonoidal glycoside designated as acacetin-7-O-galacturonide (9), alongside with nine known flavonoids; 6-methoxy-apigenin (hispidulin) (1), acacetin (2), apigenin (3), luteolin (4), kaempferol (5), eriodictyol (6), apigenin-7-O-glucoside (7), luteolin-7-O-glucoside (8), and kaempferol-3-O-rutinoside (10). The compounds were assayed for their hepatoprotective activity against CCl4-induced hepatic cell damage in rats and free radical scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH). Compounds 4, 6, 9, and 10 have not been previously reported from flowers of O. alexandrinum L., and this is the first report of acacetin-7-O-galacturonide (9) in nature which has also shown significant hepatoprotective and free radical scavenging effects. The isolated compounds were identified using different spectroscopic methods (UV, 1H NMR, 13C NMR, HMQC, HMBC, and COSY).

Hepatoprotective and neuroprotective activity of liposomal quercetin in combating chronic arsenic induced oxidative damage in liver and brain of rats

Context: Arsenic is a naturally occurring toxicant that causes acute and chronic adverse health effects, including cancer.Objective: The study was performed to evaluate the therapeutic efficacy of liposome entrapped flavonoidal quercetin in combating arsenic toxicity mediated oxidative damage in hepatocytes and brain cells in rat model.Materials and methods: Hepatic and neuronal cell damage in rats was made by daily arsenic (6mg/kg b wt, 9 mg/kg b wt and 12 mg/kg b wt) treatment via oral route for four consecutive months. Liposomal quercetin (2.71mg QC/kg b. wt) were injected s.c. on rats treated with 12 mg/kg b. wt. NaAsO2 twice a week for four months.Results and Discussion: Inorganic arsenic deposition was found to be most significant in hepatic (9.32 ± 0.100 µg/g tissue) and neuronal (6.21 ± 0.090 µg/g tissue) cells of rats treated with 12 mg/kg b wt of arsenite. Antioxidant levels in hepatic and neuronal cells were reduced significantly by the induction of arsenic. Liposomal quercetin was found most potent for a complete prevention of arsenite-induced reduction in antioxidant levels in the liver and brain of rats. Arsenic induced a substantial increase in hepatic hydroxyproline (HP) and Liposomal quercetin treatment resulted in complete replenishment of the HP level to normal. Liposomal quercetin completely prevented the arsenite-induced upregulation of cytochrome c expression in liver and brain significantly suggesting that the protective effect of Liposomal quercetin could be related to the reduction of arsenic deposition in both the organs. Conclusion: Thus, Liposomal quercetin might prove to be of therapeutic potential against arsenite-induced hepatic and neuronal cell damage in rats.

Hepatoprotective and cytotoxic activities of Delonix regia flower extracts

Fractionation of the ethanolic extract of the flowers of Delonix regia led to the isolation of three sterols, namely, stigmasterol (1.54 %), ß-sitosterol and its 3-O-glucoside (6.93 %), a triterpene, namely, ursolic acid (3.61 %) and four flavonoids: quercetin (2.92 %), quercitrin (0.59 %), isoquercitrin (3.87 %) and rutin (5.12 %) in addition to the amino acid L- azeditine-2-carboxylic acid. The structures of the isolated compounds were established on the basis of physicochemical properties and spectral analysis (IR, UV, EI/MS, 1H-NMR and 13C-NMR). The concentration of the isolated compounds was determined by HPLC technique. The ethanolic extract and its non-polar and flavonoid rich fraction as well as the isolated compounds evidenced cytotoxic activities against human liver cancer cell line (HEPG2) which were potent for ursolic acid (IC50 0.55 μg/ml) and L-azeditine-2-carboxylic acid (IC50 2.51 μg/ml). Meanwhile, rutin and isoquercitrin were inactive. Moreover, the ethanolic extract and its two fractions were tested for hepatoprotective activity against CCl4 induced hepatic cell damage in rats at two dose levels (50 and 100 mg/kg), and the flavonoid rich fraction showed statistically significant hepatoprotection at 100 mg/kg. The presence of the aforementioned flavonoids with their efficient free radical scavenging properties may explain this liver protection ability. This could suggest the use of the ethanolic extract of the flowers of D. regia as a chemopreventive agent against the two main causes of liver damage; liver toxicity by chlorinated agents and liver cancer.

15-Deoxy-Δ12,14-prostaglandin J2 prevents inflammatory response and endothelial cell damage in rats with acute obstructive cholangitis

Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-gamma (PPARgamma), such as 15-deoxy-Delta(12,14)-prostaglandin J(2) (15D-PGJ(2)), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ(2) treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (Sham+Saline), sham operation with intraperitoneal LPS infusion (Sham+LPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDL+Saline), and BDL with LPS infusion into the bile duct (BDL+LPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the Sham+LPS and the BDL+LPS group were divided into two groups (with and without 15D-PGJ(2) treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDL+LPS group compared with those in the BDL+Saline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ(2) significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ(2) in the BDL+LPS group. These results clearly demonstrate that 15D-PGJ(2) inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.

Olfactory Bulbectomy Induced Oxidative and Cell Damage in Rat: Protective Effect of Melatonin

In this study we analyzed the effects of melatonin (Mel, 1 mg/kg ip) on behavioral changes as well as cell and oxidative damage prompted by bilaterally olfactory bulbectomy. Olfactory bulbectomy caused an increase in lipid peroxidation products and caspase-3, whereas it prompted a decrease of reduced glutathione (GSH) content and antioxidative enzymes activities. Additionally, olfactory bulbectomy induced behavioral changes characterized by the enhancement of immobility time in the forced swim test and hyperactivity in the open field test. All these changes were normalized by treatment of Mel (14 days). Our data show that Mel has a beneficial neuropsychiatric action against oxidative stress, cell damage and behavior alterations.