Moringa oleifera-based diet protects against nickel-induced hepatotoxicity in rats

Multiple health-promoting effects have been attributed to the consumption of Moringa oleifera leaves, as part of diet without adequate scientific credence. This study evaluated the effect of M. oleifera-based diets on nickel (Ni) - induced hepatotoxicity in rats. Male rats assigned into six groups were given oral administration of 20 mg/kg body weight nickel sulfate in normal saline and either fed normal diet or M. oleifera-based diets for 21 days. All animals were sacrificed under anesthesia 24 hours after the last treatment. Ni exposure elevated the rat plasma activities of alanine transaminase, aspartate transaminase and alkaline phosphatase significantly. Ni exposure also raised the levels of triglyceride, total cholesterol and low-density lipoprotein cholesterol while depleting the high-density lipoprotein cholesterol concentration. Further, Ni exposure raised rat plasma malondialdehyde but depleted reduced glutathione concentrations. The histopathological presentations revealed inflammation and cellular degeneration caused by Ni exposure. We show evidence that M. oleifera-based diets protected against Ni-induced hepatotoxicity by improving the rat liver function indices, lipid profile as well as restoring cellular architecture and integrity. Study lends credence to the health-promoting value of M. oleifera as well as underscores its potential to attenuate hepatic injury.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Gastro-protective effect of Crossopteryx febrifuga in Wistar rats

Preparations of Crossopteryx febrifuga (Afzel.) Benth. (Rubiaceae) are widely used in Northern Nigeria in the therapeutic management of trypanosomiasis, malaria and painful inflammatory disorders. Previous studies have shown that the methanolic stem bark extract of Crossopteryx febrifuga possesses significant analgesic and anti-inflammatory properties possibly mediated via Non-selective inhibition of cyclo-oxygenase pathways. In the present study, the methanolic stem bark extract of Crossopteryx febrifuga was evaluated against ethanol- and piroxicam-induced ulceration in rats. Histopathological studies of the rat stomach tissues were also carried out in order to determine its safety profile on the gastrointestinal tract (git). The extract (25, 50 and100 mg extract/kg body weight) significantly (P<0.05) and dose-dependently reduced ulcer index induced by ethanol (24 - 92%) and piroxicam (81.81- 98.60%). Histopathology of the rat stomach tissues from control and extract-treated groups at 25 mg/kg body weight extract showed mild inflammation characterized by infiltration of inflammatory cells, while the extract treated groups at 50 and 100mg/kg body weight and 200 mg misoprostol/kg body weight group showed no obvious lesions. These results showed that the extract had no deleterious effects and was cytoprotective on the gastrointestinal tract (git). It can thus be developed as a safe alternative to conventional non-steroidal anti-inflammatory drugs (NSAIDs) for the management of painful inflammatory disorders.     

Protective effects of Picorrhiza kurroa extract against 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats.

Picrorrhiza kurroa has been shown to impart significant hepatoprotective activities, partly by modulation of free radical--induced lipid peroxidation. Lipid peroxidation and reactive oxygen species are associated with hepatic injury. The effect of P. kurroa treatment on the antiproliferative response and, hepatic antioxidant enzymes of rats administered with 2-acetylaminofluorene (2-AAF) was studied in Wistar rats. 2-AAF (50 mg/kg body weight, i.p.) enhances hepatic lipid peroxidation, with reduction in hepatic glutathione content, glutathione peroxidase, glutathione reductase, catalase, and glutathione-s-transferase. There was an increase in the levels of transaminase enzymes and LDH. 2-AAF treatment also enhanced ornithine decarboxylase (ODC) activity and [3H] thymidine incorporation into hepatic DNA. Pretreatment of rats orally with P. kurroa extract (250 and 500 mg/kg body weight) resulted in significant decrease in lipid peroxidation, transaminase enzymes, LDH, hepatic ODC activity, and DNA synthesis (p < 0.001). Hepatic glutathione content (p < 0.001), glutathione metabolizing enzymes (p < 0.001), and antioxidant enzymes were also recovered to significant level (p < 0.001).     

Protective effect of rapamycin against acrylamide-induced hepatotoxicity: The associations between autophagy,apoptosis, and necroptosis

Acrylamide (ACRL) was demonstrated to induce hepatotoxicity and programmed cell death (PCD). Rapamycin (RAPA)-induced autophagy had been reported to limit the progression of hepatocellular injury in experimental models. This research was designed to study two death pathways involved in ACRL-induced hepatotoxicity and the modulating effect of RAPA on the resulting hepatic injury. Thirty-six adult male rats were divided into three groups: control group, ACRL-treated group (20 mg kg/day), and the last group co-treated with ACRL plus RAPA (0.5 mg kg/day). Drugs were administered for 21 days via oral gavage. Blood samples were collected to assess alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Livers were dissected; parts were used for detection of superoxide dismutase (SOD) and malondialdehyde (MDA) tissue levels. Other parts were processed for hematoxylin and eosin, Masson's trichrome staining, immunostaining for microtubule-associated proteins 1A/1B light chain 3B (LC3), ubiquitin-binding protein (p62), caspase-3, and receptor-interacting protein kinase 1 (RIPK1). ACRL induced a significant elevation in ALT, AST, MDA levels, and reduction in the SOD level. ACRL also induced hepatocellular injury, fibrosis, and defective autophagy indicated by elevation of LC3 and p62 and increased p62/LC3 ratio. Moreover, it increased the apoptotic (caspase-3) and necroptotic (RIPK1) markers expression. RAPA significantly reduced liver enzymes, oxidative stress, fibrosis, and improved liver histology. Moreover, RAPA decreased p62/LC3 ratio indicated enhanced autophagy, and significantly reduced caspase-3 and RIPK1 expression. In conclusion, RAPA maintained autophagic activity which may save the hepatocytes from PCD and enhance cell viability.     

Preliminary study on the protective effect of vitamin C on monosodium glutamate-induced hepatotoxicity in rats

Monosodium glutamate (MSG) is a food additive with a wide range of biological effects but its high dose and prolonged use can cause a toxic effect on the liver. Therefore, the present study was aimed at investigating the role of vitamin C in MSG-induced hepatotoxicity in rats. MSG was administered to rats (by gavage) at a dose of 6 mg/g body weight for 10 days to induce hepatotoxicity, and vitamin C at a dose of 500 mg/kg body weight was coadministered to evaluate its ameliorating effect by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in serum; superoxide dismutase (SOD) and catalase activities in liver fraction; lipid peroxidation; and liver weight. It was found that MSG significantly (P?<?0.05) induced lipid peroxidation (LPO), increased liver weight, and increased activity of SOD and catalase in the liver of animals. The activity of ALT and AST was also increased in the serum on MSG administration. Vitamin C (500 mg/kg) coadministered with MSG significantly reduced LPO and liver weight and decreased the hepatic activity of catalase, but the activity of SOD was not reduced significantly. Also, a significant reduction in ALT and AST activity was observed. MSG induced oxidative stress and hepatic toxicity in the experimental animals at a dose of 6 mg/g body weight. Vitamin C significantly reduced the oxidative stress and hepatic toxicity induced by MSG, thereby providing a protective effect against the MSG-induced hepatotoxicity. The protective effect is associated with decreased LPO and liver weight and decreased activities of catalase, ALT, and AST.     

Resveratrol reduces light and electron microscopic changes in acetaminophen-induced hepatotoxicity in rats: Role of iNOS expression

Introduction: Hepatotoxicity is a major complication of acetaminophen (APAP), a widely used analgesic and antipyretic drug. Resveratrol (RSV) is a naturally occurring diphenol and it has anticancer, antioxidant, and anti-inflammatory properties. Objectives: In this study, the beneficial effects of RSV on APAP-induced hepatotoxicity was investigated in rats. Materials and methods: Group 1: Ethanol, Group 2: Saline, Group 3: RSV (10 mg/kg/ip), Group 4: APAP (1000 mg/kg/ip/single dose), Group 5: APAP+RSV (20 min after administration of APAP). The rats were sacrificed 24 h after administration of APAP. Light and electron microscopic changes were evaluated. Levels of malondialdehyde (MDA) and glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) activities were determined in liver tissue. Results: Rats of the ethanol, saline, and RSV groups did not present any histopathological alterations. In the APAP group, we observed vascular congestion, necrosis, inflammation, sinusoidal dilatation, and loss of glycogen content. In the APAP+RSV group, these changes were markedly reduced. iNOS immunostaining showed very weak positive stained hepatocytes the sections of control, saline, and RSV groups. However, in the APAP group, iNOS immunostaining was most evident in pericentral hepatocytes. In the same areas in APAP+RSV group, intensity of iNOS immunostaining decreased. A significant increase in MDA and decreases in GSH level, CAT, and SOD activity indicated that APAP-induced hepatotoxicity was mediated through oxidative stress. Significant beneficial changes were noted in tissue oxidative stress indicators in rats treated with RSV. Conclusion: These biochemical, histopathological, and ultrastructural findings revealed that RSV reduced the severity of APAP-induced alterations in liver.     

Effect of hepatoprotective agents thioctacid and flavobion on histones in the intact and regenerating liver of irradiated rats

Department of Cellular and Molecular Biology, Faculty of Science, P. J. afarik University, Koice, Czechoslovakia. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 113, No. 2, pp. 191–193, February, 1992.     

Potential protective effect of honey against chronic cerebral hypoperfusion-induced neurodegeneration in rats

IntroductionTo investigate the neuroprotective potential of Malaysian Tualang honey in chronic cerebral hypoperfusion induced by permanent bilateral common carotid arteries ligation (2VO) in rats.MethodsRats were randomly divided into three groups (n = 10); sham control, honey-untreated 2VO group “2VO” and honey treated 2VO group “2VO + H”. At 10th week of 2VO surgery, all the rat were sacrificed, brains were dissected out, the right hemisphere was processed for histological study, neuronal counts were performed on cresyl violet-stained sections, the number of viable neurons in CA-1 region of the hippocampus were analysed and counted.ResultsThere were damaged, distorted, irregular cells with shrunken cytoplasm and dark pykonotic nuclei in “2VO” rats. Treatment of rats with honey restored the hippocampal cells to their normal structure and reduced loss of neurons in “2VO + H” rats as compared with “2VO” rats.DiscussionThis study shows that Malaysian Tualang honey might have therapeutic potential for the treatment of chronic cerebral hypoperfusion related neurodegenerative disorders.     

The protective effect of dl-tetrahydropalmatine against the development of amygdala kindling seizures in rats

The influence of dl-tetrahydropalmatine (THP), an active component isolated from a Chinese herbal medicine corydalis, was tested on the development of electrically kindled amygdala. The seizure activity was quantified by a ultrasonic system for vertical motion measurements. Intraperitoneal injection of THP (20 or 30 mg kg⁻¹) 30 min before applying the daily kindling stimulus prevented the development of the kindling process. The behavioral seizure score and the motion responses which normally develop during electrical kindling were reduced below their initial values. The results suggest that THP is a very effective antiepileptogenic and anticonvulsant agent when applied to electrically kindled rats.     

A comparison of hepatoprotective activity of Bacoside to Silymarin treatment against a combined Isoniazid and Rifampin-induced hepatotoxicity in female Wistar rats

ABSTRACT

The liver is an important organ that plays a vital role in homeostasis maintenance and regulation. Any liver damage or injury caused by drugs or chemicals is called hepatotoxicity. Isoniazid and rifampin are drugs used separately to treat tuberculosis but have unique side effects and potential hepatotoxicity. The metabolism of isoniazid (INH) and rifampin (RIF) takes place in liver hence hepatotoxicity is the main cause of their continuous use. Bacoside was obtained from the plant Bacopa monnieri, a dammarene type triterpenoid saponin, found distributed throughout India. Bacoside has been used as a nerve tonic, a free radical scavenger, and antioxidant. It is known that the combined INH-RIF induced hepatotoxicity can be antagonized by maintaining hepatocyte membrane integrity in rats. Silymarin, an herbal drug, and its component silybin were reported to work as lipid peroxidation inhibitors and antioxidants which scavenge free radicals. Due to minimal toxicity and no adverse drug interactions, Silymarin is used to treat various medically confirmed hepatic disorders. The aim of this study was to evaluate the beneficial effect of Bacoside against INH- and RIF-induced toxicity in livers of Wistar albino rats. Four experimental groups of rats were used to study four parameters; bodyweight, liver enzyme markers, liver antioxidant, and liver histopathology. INH- and RIF-treated rats showed abnormalities in liver markers which were normalized by Bacoside and that seems similar to the normal control and Silymarin-treated groups. Thus, the current study demonstrated the hepatoprotective effect of Bacoside against INH- and RIF-induced toxicity in Wistar albino rats.     

Danshensu-mediated protective effect against hepatic fibrosis induced by carbon tetrachloride in rats

The culprit of hepatic fibrosis (HF) is linked to suprathreshold deposition of collagen. Thus, collagen reduction by improved metabolism contributes to HF management. In this study, we aimed to investigate the hepatoprotective effects of Danshensu (DSS) against carbon tetrachloride (CCl₄)-induced HF rats. The results showed that DSS-administrated rats resulted in decreasing in hepatosomatic indexes, and lowering serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were increased, while the content of malonaldehyde (MDA) was lessened in liver tissue of DSS administration group. In addition, the pro-fibrotic markers of hydroxyproline (Hyp), type III procollagen (PCIII) and hyaluronic acid (HA) contents were decreased. Histopathological examination confirmed that the hepatotoxicity in CCl₄-injured rats was alleviated following the DSS administration. Furthermore, intrahepatic protein expressions of alpha-smooth muscle actin (α-SMA), phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) were effectively down-regulated, respectively. Overall, this work demonstrates that DSS played the protective effect against CCl₄-induced cytotoxicity in liver tissue, which the probable mechanism is associated with attenuation of lipid peroxidation, collagen accumulation and enhancement of anti-oxidative defense capability, as well as regulation of intrahepatic JAK/STAT pathway for maintaining collagenic homoeostasis.     

Toxic effect of an antitumor drug paclitaxel on morphofunctional characteristics of the liver in rats

Single intravenous injection of paclitaxel to rats in a maximum tolerated dose of 4.6 mg/kg was accompanied by permanent structural and functional changes in the liver. The observed changes were typical of nonspecific reactive hepatitis: infiltration with lymphocytes and macrophages, pyknosis, and focal fatty degeneration of hepatocytes. Liver enzyme activity increased in blood plasma. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 225–228, February, 2008     

Hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity in rats

Abstract

Objectives: Several studies demonstrated the antioxidant and anti-inflammatory role of melatonin and celecoxib. This study is designed to explore the underlying mechanism of hepatoprotective effects of melatonin and celecoxib against ethanol-induced hepatotoxicity by morphological, and biochemical approaches.

Materials and methods: Adult male rats were divided into five groups: saline, ethanol, melatonin, and celecoxib were administered for 11 consecutive days after ethanol injection. Biochemical analyses were performed for the determination of glutathione (GSH), glutathione S-transferase (GST), and inducible nitric oxide (iNOS). Immunohistochemistry was performed to determine the level of different inflammatory markers.

Results: Histopathological results showed that ethanol-induced marked hepatic injury leads to cloudy swelling, hydropic degeneration, apoptosis, and focal necrosis in all hepatic zones. Biochemical analysis revealed significant increases in serum transaminases and alkaline phosphatase in the ethanol group. Oxidative stress associated with attenuated antioxidant enzymes was also spotted in the ethanol group, as ethanol down-regulated GSH, GST, and upregulated NO. Additionally, ethanol increased the activation and the expression of tumor necrotic factor (TNF-α), p-NF_KB, and COX2. Finally, hepatic cellular apoptosis was clearly obvious in ethanol intoxicated animals using activated JNK staining.

Conclusion: These results provided pieces of evidence that the hepatoprotective effect of melatonin and celecoxib is possibly mediated through the modulation of JNK and TNF-α signaling pathways with subsequent suppression of inflammatory and apoptotic processes.     

氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响

目的研究氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响。方法建立野百合碱-1-1诱导的肺动脉高压大鼠模型,将大鼠随机分为4组:对照组、野百合碱组、氟西汀低剂量(2mg·kg·d)组、-1-1氟西汀高剂量(10mg·kg·d)组。观察各组大鼠血流动力学与肺小动脉形态学的变化,Western blot方法检测ROCK1与ROCK2的蛋白表达,以及MYPT1的磷酸化。结果野百合碱诱导大鼠肺动脉压力升高、肺动脉重构、肺组织炎症反应,上调大鼠肺组织中ROCK1与ROCK2以及增加Rho激酶的活性;氟西汀剂量依赖地抑制这些改变。结论氟西汀抑制野百合碱诱导的大鼠肺动脉高压,与抑制Rho激酶活性有关。     

Effects of adrenergic agents on stress-induced brain microstructural and immunochemical changes in adult male Wistar rats

This preliminary study aims to explore how adrenergic agents modulate stress response and affect stress-induced behavioral and brain changes in rodents. A total of 40 adult male Wistar rats were subjected to chronic unpredictable mild stress (CUMS) and randomly divided into five groups. At 30 min before daily stress exposure, the rats were intraperitoneally injected with phentolamine (5 mg/kg), noradrenalin (1.0 mg/kg), propranolol (10 mg/kg), isoproterenol (0.05 mg/kg) or saline, respectively. Another 8 rats served as normal control and received daily saline injection without stress exposure. Open-field behaviors were tested at 1 day after the end of the 21 days of stress exposure. Blood samples were collected for serum corticosterone measurement. Brain sections containing hippocampus were stained with hematoxylin and eosin (H&E) as well as by immunohistochemistry for heat shock protein 70 (hsp70) and nitric oxide synthase type 2 (nos2) analyses. The experimental results demonstrated that repetitive dosing of noradrenalin, phentolamine, and propranolol during chronic stress might region-dependently attenuate stress-induced microstructural and biochemical changes in the hippocampus, although propranolol intensified stress-induced behavioral changes.     

The protective effect of grape skin or purple carrot extracts against cadmium intoxication in kidney of rats

The aim of this study was to evaluate the protective effect of grape skin or purple carrot extracts against cadmium-induced intoxication in rats’ kidneys. For this purpose, 30 male Wistar rats were distributed into six groups (n = 5), as follows: control group; cadmium group and groups treated with grape skin at 175 or 350 mg / L doses; or purple carrot extract at 400 mg / L or 800 mg / L doses, by drinking water. In the group exposed to cadmium, histopathological analysis revealed severe tissue injury as a result of coagulation necrosis, congested vessels and inflammatory infiltrate. Animals treated with grape skin or purple carrot extracts improved the histopathological changes induced by cadmium. 8-OHdG immunoexpression and catalase gene expression decreased in rats treated with purple carrot or grape skin extracts. Grape skin extract was able to increase SOD-CuZn gene expression as well. Toll-like signaling pathway (TLR2, PIKK and TRAF6) and cytochrome c expressions were not altered after the treatment with grape skin or purple carrot extracts. Taken together, we conclude that grape skin and purple carrot extracts had a protective effect on the rats’ kidneys after cadmium intoxication, by means of tissue regenerating tissue regeneration and antioxidant properties, grape skin extract being more effective for this purpose.     

Olmesartan restores the protective effect of remote ischemic perconditioning against myocardial ischemia/reperfusion injury in spontaneously hypertensive rats

OBJECTIVES:Remote ischemic perconditioning is the newest technique used to lessen ischemia/reperfusion injury. However, its effect in hypertensive animals has not been investigated. This study aimed to examine the effect of remote ischemic perconditioning in spontaneously hypertensive rats and determine whether chronic treatment with Olmesartan could influence the effect of remote ischemic perconditioning.METHODS:Sixty rats were randomly divided into six groups: vehicle-sham, vehicle-ischemia/reperfusion injury, vehicle-remote ischemic perconditioning, olmesartan-sham, olmesartan-ischemia/reperfusion and olmesartan-remote ischemic perconditioning. The left ventricular mass index, creatine kinase concentration, infarct size, arrhythmia scores, HIF–1α mRNA expression, miR-21 expression and miR-210 expression were measured.RESULTS:Olmesartan significantly reduced the left ventricular mass index, decreased the creatine kinase concentration, limited the infarct size and reduced the arrhythmia score. The infarct size, creatine kinase concentration and arrhythmia score during reperfusion were similar for the vehicle-ischemia/reperfusion group and vehicle-remote ischemic perconditioning group. However, these values were significantly decreased in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group. HIF–1α, miR-21 and miR-210 expression were markedly down-regulated in the Olmesartan-sham group compared to the vehicle-sham group and significantly up-regulated in the olmesartan-remote ischemic perconditioning group compared to the olmesartan-ischemia/reperfusion injury group.CONCLUSION:The results indicate that ¹ the protective effect of remote ischemic perconditioning is lost in vehicle-treated rats and that chronic treatment with Olmesartan restores the protective effect of remote ischemic perconditioning; ² chronic treatment with Olmesartan down-regulates HIF–1α, miR-21 and miR-210 expression and reduces hypertrophy, thereby limiting ischemia/reperfusion injury; and ³ recovery of the protective effect of remote ischemic perconditioning is related to the up-regulation of HIF–1α, miR-21 and miR-210 expression.