Effect of Epigallocatechin-3-gallate on Stress-Induced Depression in a Mouse Model: Role of Interleukin-1ß and Brain-Derived Neurotrophic Factor.

Epigallocatechin 3-gallate (EGCG) is a natural polyphenolic antioxidant in green tea leaves with well-known health-promoting properties. However, the influence of EGCG on a chronic animal model of depression remains to be fully investigated, and the details of the molecular and cellular changes are still unclear. Therefore, the present study aimed to investigate the antidepressant effect of EGCG in mice subjected to chronic unpredictable mild stress (CUMS). After eight consecutive weeks of CUMS, the mice were treated with EGCG (200 mg/kg b.w.) by oral gavage for two weeks. A forced swimming test (FST) was used to assess depressive symptoms. EGCG administration significantly alleviated CUMS-induced depression-like behavior in mice. EGCG also effectively decreased serum interleukin-1ß (IL-1ß) and increased the mRNA expression levels of brain-derived neurotrophic factor (BDNF) in the hippocampal CA3 region of CUMS mice. Furthermore, electron microscopic examination of CA3 neurons in CUMS mice showed morphological features of apoptosis, loss or disruption of the myelin sheath, and degenerating synapses. These neuronal injuries were diminished with the administration of EGCG. The treatment effect of EGCG in CUMS-induced behavioral alterations was comparable with that of clomipramine hydrochloride (Anafranil), a tricyclic antidepressant drug. In conclusion, our study demonstrates that the antidepressive action of EGCG involves downregulation of serum IL-1ß, upregulation of BDNF mRNA in the hippocampus, and reduction of CA3 neuronal lesions.

Beneficial role of naringin against methotrexate-induced injury to rat testes: biochemical and ultrastructural analyses.

BACKGROUND: Methotrexate (MTX) is a commonly used chemotherapeutic drug that has adverse toxic effects on germ cells. Naringin (NG) is a natural flavanone glycoside, with different phytotherapeutic applications, and its possible protective effects against MTX-induced testicular tissue damage were investigated in this study. METHODS: Low and high doses of NG (40 and 80 mg/kg/day) were given for 10 days by intraperitoneal (i.p.) injection and MTX (20 mg/kg i.p.) was given at the 4th day of the experiment, with or without NG in rats. RESULTS: The obtained results showed that exposure to MTX increased malondialdehyde (MDA) levels and nitric oxide (NO) production compared with the control. In the meantime, MTX depleted catalse (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), and reduced glutathione (GSH) in the testicular tissue. Further, serum testosterone levels were significantly decreased in the MTX group. NG significantly counteracted the aforementioned effects of MTX; however, NG80 was more effective in restoring SOD, GR, MDA and NO. Interestingly, NG80 achieved a better improvement in the ultrastructural pattern of the testicular cells in MTX-exposed rats. CONCLUSION: These results indicated, for the first time, that NG could be a potential candidate therapy against MTX-reprotoxic impacts.

Nephroprotective effect of naringin in methotrexate induced renal toxicity in male rats.

The current work aims to study the nephroprotective potential of naringin (NG), a flavanone derived from citrus fruits, in methotrexate (MTX)-induced renal toxicity. Thirty male rats were divided into five groups; control group (IP saline), MTX group (IP single dose, 20 mg/kg), and three groups co-treated with MTX and naringin (IP daily dose; 20, 40, and 80 mg/kg, respectively). Kidney tissues were used to investigate renal function, oxidative stress, lipid peroxidation, and caspase-3 activity. Biochemical cytokine analysis was performed in addition to ultrastructural examinations of kidney tissue. When compared to the MTX-treated rats, MTX+NG significantly reduced the levels of urea, creatinine, MDA, NO, TNFα, IL-6, and caspase-3 activity. A significant increase in the levels of the antioxidant enzymes and GSH were also noted. Additionally, naringin ameliorated the apparent ultrastructural changes observed in the glomeruli and renal tubules of MTX-intoxicated rats. Noticeable structural improvements of glomerular lesions, proximal, and distal convoluted tubular epithelium were observed in MTX+NG treated animals, including podocytes with regular foot processes, perfectly organized filtration barrier, no signs of GBM thickening, organized brush border, and normal architecture of microvilli. Naringin (80 mg/kg) had the maximum amelioration effect. To the best of our knowledge, this is the first study to investigate the ultrastructural manifestations of naringin and/or MTX on the kidney of rats. Taken all, naringin has a potent therapeutic effect and can be used in adjuvant therapy to prevent MTX-induced nephrotoxicity. Nevertheless, the molecular mechanism underlying the nephroprotective capacity of naringin needs further investigation.

Hepatoprotective effect of Spirulina platensis against carbon tetrachloride-induced liver injury in male rats.

OBJECTIVES: Spirulina platensis (SP) is an edible Cyanobacterium with ethnomedicinal significance. This study aims at evaluating the beneficial effect of SP against carbon tetrachloride (CCl4)-induced liver toxicity in male rats. METHODS: Rats received intraperitoneal injections of CCl4 (2 ml/kg body weight [b.w.] per every other day) for 40 days, alone or in combination with oral treatments of SP (400 mg/kg b.w. per day). KEY FINDINGS: SP attenuated haematological disturbances, serum liver markers, hepatic necrosis and inflammation, and dyslipidemia in CCl4-intoxicated rats. SP also reduced CCl4-induced oxidative stress by increasing the activities of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase and glutathione content, and inhibiting lipid peroxidation products and nitric oxide levels in the rat liver. Further investigations revealed that SP counteracted CCl4-induced increased hepatic levels of Ki-67 (a parameter of cell proliferation), interleukin-6, and tumour necrosis factor-alpha and cyclooxygenase-2 messenger RNA expression. Noticeably, the supplementation of SP restored the decrease of proapoptotic p53 protein levels in the liver of rats treated with CCl4. CONCLUSIONS: SP prevented liver damage in CCl4-treated rats via augmentation of antioxidant defense mechanisms and inhibition of inflammatory cytokines/mediators and antiproliferative effects.

Analysis of silymarin-modulating effects against acrylamide-induced cerebellar damage in male rats: Biochemical and pathological markers.

BACKGROUND: Acrylamide (ACR) is a well-proven neurotoxin and potential food carcinogen in humans and rodent models. Silymarin (SIL) is a flavonoid mixture isolated from seeds, leaves, and fruits of Silymarin marianum (milk thistle) that possesses a free-radical scavenging effect. OBJECTIVE: In this work, the primary focus was to investigate the efficacy of SIL to mitigate ACR-induced subacute neurotoxic effects and oxidative changes in rat cerebellum. METHODS: Adult male rats were treated intraperitoneally with ACR (50 mg/kg) with or without SIL (160 mg/kg). The neuropathology and biochemical parameters viz. lipid peroxidation (measured as levels of malondialdehyde or MDA), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), serotonin (5-hydroxytryptamine; 5-HT), dopamine (DA), and cathepsin D (CTSD) in the cerebellum have been evaluated. RESULTS: The data showed that ACR induced redox disruptions as measured by increased MDA levels and inhibition of CAT, SOD, and GPx antioxidant enzyme activities. Besides, cerebellar monoamine neurotransmitters, 5-HT and DA, were depleted in ACR-treated rats. Furthermore, ACR administration caused a significant elevation of CTSD activity, indicating that ACR could trigger apoptosis or apoptosis-like death. At the tissue level, cerebellar cortex sections from ACR-treated animals were characterized by severe neuronal damage. The administration of SIL to ACR-treated rats remarkably alleviated all the aforementioned ACR-induced effects. CONCLUSION: SIL has a potent therapeutic effect against ACR-induced cerebellar neurotoxicity in experimental rats via the attenuation of oxidative/antioxidative responses and the inhibition of CTSD-activity.

Naringin alleviates methotrexate-induced liver injury in male albino rats and enhances its antitumor efficacy in HepG2 cells.

Methotrexate (MTX) is an efficient chemotherapeutic and immunosuppressant drug, but the hepatotoxicity of MTX limits its clinical use. Naringin (Nar) is a flavonoid derived from Citrus paradise, and has been shown to possess several pharmacological activities, including free-radical scavenging and antioxidant properties. In the present study, we first tested the possible protective effects of multiple doses of Nar against MTX-induced acute hepatotoxicity in rats, and then we investigated the growth inhibition and apoptotic effects of MTX and/or Nar against the HepG2 hepatocarcinoma cell line. Our in vivo results showed that Nar significantly reduced MTX-induced increases in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin levels. Nar also reduced MTX-induced oxidative stress by significantly reducing liver malondialdehyde (MDA) and nitric oxide (NO) content and increasing superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione (GSH). In addition, Nar significantly counteracted MTX-induced increases in hepatic interleukin-6 and tumor necrosis factor-α (TNF-α). Further, Nar greatly protected hepatocyte ultrastructure against MTX-induced injury. In contrast, in vitro MTX and/or Nar treatment of HepG2 cells for 48 h exhibited a cytotoxic effect and induced apoptosis in a dose-dependent manner mediated by a significant increase in the Bax/Bcl-2 protein expression ratio. Noticeably, Nar potentiated the MTX effect on the Bax/Bcl-2 ratio. In conclusion, Nar decreased MTX-induced functional and ultrastructural liver damage in a tumor-free animal model. Also, our data introduce MTX and Nar as promising antiproliferative agents with a distinctive mode of action, inducing apoptosis in HepG2 tumor cells through activation of Bax and down-regulation of Bcl-2 protein expression.

Oral Supplements of Ginkgo biloba Extract Alleviate Neuroinflammation, Oxidative Impairments and Neurotoxicity in Rotenone-Induced Parkinsonian Rats.

BACKGROUND: Ginkgo biloba extract (GbE) is known to contain several bioactive compounds and exhibits free radical scavenging activity. Parkinson's Disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and is associated with oxidative stress, neuroinflammation and apoptosis. OBJECTIVE: The current study aimed to investigate the neuroprotective effect of GbE in a rat model of PD induced by rotenone (ROT; a neurotoxin). METHODS: Twenty-four male albino rats were randomly divided into four groups of six rats each: normal control, GbE treated, toxin control (ROT treated) and GbE+ROT group. RESULTS: Oral administration of ROT (2.5 mg/kg b.w.) for 50 days caused an increased generation of lipid peroxidation products and significant depletion of reduced glutathione, total thiol content and activities of enzymatic antioxidants, i.e., superoxide dismutase and glutathione peroxidase in the brains of treated rats. Furthermore, ROT caused an elevation in acetylcholinesterase, interleukin-1ß, interleukin- 6 and tumor necrosis factor-α and a significant reduction in dopamine in the stratum and substantia nigra. Immunohistochemical results illustrated that ROT treatment reduced the expression of tyrosine hydroxylase (TH). GbE treatment (150 mg/kg b.w./day) significantly reduced the elevated oxidative stress markers and proinflammatory cytokines and restored the reduced antioxidant enzyme activities, DA level and TH expression. These results were confirmed by histological observations that clearly indicated a neuroprotective effect of GbE against ROT-induced PD. CONCLUSION: GbE mitigated ROT-induced PD via the inhibition of free-radical production, scavenging of ROS, and antioxidant enhancement.

Rutin ameliorates carbon tetrachloride (CCl4)-induced hepatorenal toxicity and hypogonadism in male rats.

Rutin, a food derived-polyphenolic bioflavonoid, has been acknowledged for several health benefits. This study aims to explore the ameliorative effects of rutin against carbon tetrachloride (CCl4) toxicity in male rats. Adult male rats were given either CCl4 (30% in olive oil, 3 ml/kg b.w. intraperitoneally) alone or in combination with rutin (70 mg/kg intragastrically) twice a week for 4 weeks. Our data showed that rutin mitigated CCl4 hepatorenal damage, as indicated by diagnostic markers (i.e., transaminases, alkaline phosphatase, total bilirubin, total protein, albumin, urea, uric acid and creatinine), and histopathological findings. In addition, CCl4 induced profound elevation of free radical generation and oxidative stress, as evidenced by increasing lipid peroxidation and reducing catalase, superoxide dismutase and glutathione peroxidase activities in liver, kidney and testicular tissues; these effects were suppressed by coexposure with rutin. Moreover, the increase in the levels of serum triglycerides, cholesterol, low-density lipoprotein cholesterol, and very-low-density lipoprotein cholesterol induced by CCl4 was effectively counteracted by rutin. The decrease in the level of high-density lipoprotein cholesterol in the CCl4 group was also counteracted by rutin treatment. Interestingly, the decreased levels of hormonal mediators associated with sperm production, including serum testosterone, luteinizing hormone and follicle-stimulating hormone, and the impaired sperm quality induced by CCl4 were reversed by rutin. Data from the current study clearly demonstrated that rutin supplementation could at least partly overcome CCl4-induced hepatotoxicity, nephrotoxicity and reproductive toxicity by antioxidant and antidyslipidemic effects.

A simple and reliable protocol for long-term culture of murine bone marrow stromal (mesenchymal) stem cells that retained their in vitro and in vivo stemness in long-term culture.

BACKGROUND: Bone marrow derived stromal stem cells (BMSCs) are a clonogenic cell population that is characterized by self-renewal capacity and differentiation potential into osteoblasts, and other mesenchymal cell types. Mouse BMSCs (mBMSCs) are difficult to be cultured and propagated in vitro due to their replicative senescent phenotype, heterogeneity and high contamination with plastic adherent hematopoietic progenitors (HPCs). In this study, we described long-term culture of homogenous population of mBMSCs using simple and highly reproducible approach based on frequent subculturing (FS) at fixed split ratio in the presence of basic fibroblast growth factor (bFGF). RESULTS: Cultured mBMSCs using this protocol (mBMSCs-FS) showed long-term survival in culture > 70 population doubling (PD) and retained their characteristic surface markers and differentiation capacity into osteoblast and adipocyte lineages. When compared to the clonal bone marrow-derived cell line ST2, mBMSCs-FS displayed more enhanced osteoblast differentiation potential and responsiveness to osteogenic factors including BMPs, IGF-1, PDGF, TGFß1,3, FGF, cAMP, Wnt3a and VEGF. In addition, unlike ST2 cells, mBMSCs-FS maintained capacity to form ectopic bone and bone marrow stroma upon in vivo transplantation in immune-compromising mice, even at high PD levels. Interestingly, by applying the same FS + bFGF protocol, we succeeded to obtain long-term cultures of primary neonatal calvarial osteoprogenitor cells (OBs) that were cultured for more than 70 PD and maintained in vitro and in vivo osteoblast differentiation capacities. CONCLUSIONS: Our data provide a simple and reliable protocol for generating long-term cultures of mBMSCs and OBs with retained high in vitro and in vivo osteoblast differentiation capacities for use in pre-clinical and molecular mechanism studies.

Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats.

The aim of this study was to evaluate the probable protective effect of quercetin (QUE) against cadmium (Cd)-induced sub-chronic toxicity in rats. Adult male rats were given either Cd (as cadmium chloride; 5 mg/kg) alone or in combination with QUE (50 mg/kg) daily for 4 weeks by oral gavage. At the end of the experimental period, Cd accumulation, and selected hematological, thyroid, and reproductive markers were assessed. Results revealed that Cd treatment significantly increased Cd concentrations in blood, thyroid gland, and testicular tissue of rats. Cd also caused a decline in hemoglobin content, hematocrit value, and total erythrocyte and leucocyte counts. Further, significant suppressions in the blood levels of hormones related to thyroid gland function, and male reproductive hormones (i.e., testosterone, luteinizing hormone and follicle-stimulating hormone), were observed in Cd-treated rats compared to the control. In parallel, low sperm count and sperm motility, increased sperm abnormalities, and marked pathology occurred in testis. Combination with QUE recorded amelioration of the deleterious effects of Cd, involving regulation of hematological toxicity and thyroid hormonal levels and subsequently modulation of testicular function. In conclusion, it appears that dietary QUE can rescue from Cd-induced hematological dysfunctions and testicular damage by reversing the hypothyroid state.

The Coumarin Derivative 5'-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways.

The phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5'-hydroxy auraptene (5'-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5'-HA on osteoclast differentiation of mouse bone marrow (BM) cells. The effect of 5'-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP+ multinucleated cells (TRAP+MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5'-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5'-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5'-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5'-HA in BM cells. In conclusion, we identified 5'-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.

Monitoring metal levels in water and multiple biomarkers in the grouper ( Epinephelus tauvina) to assess environmental stressors on the Arabian Gulf coast of Saudi Arabia.

In this field study, the levels of heavy metals (Pb, Fe, Co, Cu, and Zn) in water and a suite of biochemical and histological biomarkers in the grouper ( Epinephelus tauvina) were assessed at four sites in the Arabian Gulf. Samples were taken from a relatively non-urban reference site, called Salwa (S1), and three effluent-dominated sites, namely Al-aziziyah in southern Dammam city (S2), the Al-Jubail coast (S3), and Manifa (S4). Toxic metals, namely Pb and Co (at all sites) and Fe (at S3), were elevated in water samples relative to the internationally permissible limits. In fish, induced levels of heat shock protein 70 (HSP70) in the liver at S3 and S4 were higher than those of the reference fish at S1. Additionally, the level of the lipid peroxidation (LPO) product (malondialdehyde (MDA)) was significantly increased in gills (at S3) and liver (at S2 and S3). There was an inhibition of catalase activities in the gills of fish from S2 to S4 and significantly higher activity levels of superoxide dismutase in the gills of fish from S4. Histopathological features such as aneurysms in gill vessels, deformed gill lamellae, increases in liver melano-macrophage centers, and hepatocellular necrosis were most abundant at sites where significant pollution problems exist (i.e. S2-S4). The results reveal that the eastern coast of Saudi Arabia, in the Arabian Gulf, is still contaminated, as indicated by elevated HSP70, LPO content and numbers of histological lesions, and that monitoring of contaminants and their effects should be continued in this region.

Protective effect of Nigella sativa seeds against spermatocyte chromosomal aberrations and genotoxicity induced by carbon tetrachloride in mice.

Nigella sativa is a well-known dietary antioxidant and a valuable inhibitor of clastogenesis and carcinogenesis. The purpose of the present work was to investigate the effects of N. sativa seeds against chromosomal aberrations in primary spermatocytes and early embryonic lethality induced by CCl4 hepatotoxin in Swiss albino mice. One hundred male Swiss albino mice were randomly divided into five groups. Groups I, II, and III received only normal saline, olive oil, and aqueous suspension of N. sativa seeds (50 mg/kg b.w.), while groups IV and V were orally given CCl4 dissolved in olive oil at a dose level of 1.9 (» LD50) alone and with aqueous suspension of N. sativa seeds (50 mg/kg b.w.) alternately. Aqueous extract of N. sativa significantly reduced the elevated frequency of chromosomal aberrations induced by CCl4 in mouse primary spermatocytes. For the male-dominant lethal test, four males from each group (control and experimental) were used and each male was mated for 13 days to two untreated virgin females. On days 14-16 after breeding, all the females were evaluated for incidence of pregnancy, live implants, and fetal deaths. Treatment with 1/4 LD50 of CCl4 induced positive dominant lethal mutation, reflecting a high rate of deformations in male germ cells. Interestingly, no dominant lethal mutations were recorded in females mated to male mice treated with CCl4 plus N. sativa. Under the experimental conditions of this study, our results highlight the beneficial role of N. sativa against CCl4-induced mutagenicity.

N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats.

Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.

Spinosad Induces Antioxidative Response and Ultrastructure Changes in Males of Red Palm Weevil Rhynchophorus ferrugineus (Coleoptera: Dryophthoridae).

The red palm weevil, Rhynchophorus ferrugineus, is of great concern worldwide, especially in the Middle East, where dates are a strategic crop. Despite their ecological hazard, insecticides remain the most effective means of control. A bioinsecticide of bacterial origin, spinosad is effective against several pests, and its efficacy against male R. ferrugineus was assessed in the present study. The antioxidative responses of key enzymes including catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) to spinosad were investigated in the midgut and testes, and the effects of this insecticide on the cell ultrastructure of the midgut, Malpighian tubules, and testes were also determined. The lethal concentration 50 of spinosad was measured at 58.8 ppm, and the insecticide inhibited the activities of CAT, SOD, and GST in the midgut. However, no significant changes in the activities of these enzymes were observed in the testes. Spinosad treatment resulted in concentration-dependent changes in the cellular organelles of the midgut, Malpighian tubules, and testes of R. ferrugineus, and some of these effects were similar to those exerted by other xenobiotics. However, specific changes were observed as a result of spinosad treatment, including an increase in the number and size of concretions in Malpighian tubule cells and the occasional absence of the central pair of microtubules in the axonemes of sperm tails. This study introduces spinosad for potential use as an insecticide within an integrated control program against male red palm weevils. Additionally, the study provides biochemical and ultrastructural evidence for use in the development of bioindicators.

Biochemical and histopathological changes in liver of the Nile tilapia from Egyptian polluted lakes.

The aim of the present study was to analyze the impact of environmental contamination on oxidative stress and histopathologic biomarkers in liver of the Nile tilapia, Oreochromis niloticus, collected from four sites that differ in their extent of pollution load, including heavy metals: the southeast basin (SEB), main basin (MB), and northwest basin (NWB) of Lake Mariut as well as Boughaz El-Maadiya, a channel in Lake Edku. The SEB was the less-impacted site, and thus considered as a reference. High concentrations of heavy metals (cadmium, copper, iron, lead, zinc, and manganese) were detected in fish liver at sites with anthropogenic pressure. All biomarkers, lipid peroxidation (in the MB, NWB, and Lake Edku), superoxide dismutase (in the MB and NWB), and glutathione peroxidase, and reduced glutathione (in the NWB) were found to be significantly higher compared to the reference values. Catalase, glutathione reductase, and glucose-6-phosphate dehydrogenase showed a varied response and displayed significantly lower activities in the polluted sites. Certain hepatic lesions, detected microscopically, were stimulated in fish from the MB and NWB, reflecting the high contamination of these areas. These included foci of necrosis, melanomacrophage infiltration, congestion, nuclear pyknosis, and extensive vacuolation corresponding to relatively higher lipid content. Overall, our results suggest that the selected biomarkers are useful for the assessment of pollution impacts in natural aquatic environments influenced by multiple pollution sources. The existence of chronic background pollution of the test sites implies that the observed biomarker responses cannot be solely attributed to heavy metals.

Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage.

The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-ß1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.

Curcumin Ameliorates Lead (Pb(2+))-Induced Hemato-Biochemical Alterations and Renal Oxidative Damage in a Rat Model.

This study aims to evaluate the protective role of curcumin (Curc) against hematological and biochemical changes, as well as renal pathologies induced by lead acetate [Pb (CH3COO)2·3H2O] treatment. Male albino rats were intraperitoneally treated with Pb(2+) (25 mg of lead acetate/kg b.w., once a day) alone or in combination with Curc (30 mg of Curc/kg b.w., twice a day) for 7 days. Exposure of rats to Pb(2+) caused significant decreases in hemoglobin (Hb) content, hematocrit (Ht) value, and platelet (Plt) count, while Pb(2+)-related leukocytosis was accompanied by absolute neutrophilia, monocytosis, lymphopenia, and eosinopenia. A significant rise in lipid peroxidation (LPO) and a marked drop of total antioxidant capacity (TAC) were evident in the kidney, liver, and serum of Pb(2+) group compared to that of control. Furthermore, significantly high levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C), and a sharp drop in serum high-density lipoprotein (HDL-C) level were also seen in blood after injection of Pb(2+). Additionally, hepatorenal function tests were enhanced. Meanwhile, Pb(2+) produced marked histo-cytological alterations in the renal cortex. Co-administration of Curc to the Pb(2+)-treated animals restored most of the parameters mentioned above to near-normal levels/features. In conclusion, Curc appeared to be a promising agent for protection against Pb(2+)-induced toxicity.

Neuropathological effect of dimethyl disulfide on neurons of the desert locust Schistocerca gregaria.

Botanical insecticides have introduced a new concept in insecticide research. In response to insect attacks, some plants can release volatile compounds that alter insect metabolism and nervous system activity. In the present study, changes in the electrical activity of chemoreceptors and alteration of the fine structure of metathoracic ganglia of desert locust were examined after acute exposure to dimethyl disulfide (DMDS), a sulfur compound released from Allium porrum. Animals were exposed to 1/4 LC50 of DMDS (0.375 µl/L air) and electrophysiological and electron-microscopical studies were carried out. Application of DMDS showed an increase in the activity of deterrent cells present in tarsal chemosensilla of locust. On the other hand, evident degenerative changes in the neurons, neuroglia, neuropile and synaptic vesicles were observed in the metathoracic ganglia of DMDS-treated animals. These findings revealed that pest control using DMDS might be feasible and future work is highly recommended in this respect.

Hemin attenuates cisplatin-induced acute renal injury in male rats.

BACKGROUND: The aim of this study is to investigate the protective effects of hemin (the heme oxygenase-1 [OH-1] inducer) against nephrotoxic effects induced by cisplatin [cis-diamminedichloroplatinum II (CP)] in male rats. METHODS: The evaluation was performed through monitoring renal redox parameters: lipid peroxidation (LPO), glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GR), and reduced glutathione (GSH). The work also examined renal function tests (urea and creatinine), tissue proinflammatory mediator like nitric oxide (NO), and kidney cytopathology. RESULTS: A single intraperitoneal dose of CP (10 mg/kg b.w.) caused significant elevation of blood urea, serum creatinine, and renal LPO and NO, along with significant decline of the activities of GPx and GR, but renal SOD activity and GSH level were statistically insignificant as compared to control group. Subcutaneous injection of hemin (40 µmol/kg b.w.) partially ameliorated CP-induced renal damage, based on suppression of blood urea, serum creatinine, the renal MDA and NO levels, and increased antioxidant capacity in CP-treated rats. The results of histopathological and ultrastructural investigations supported the renoprotective effect of hemin against CP-induced acute toxicity. CONCLUSION: The induction of HO-1 by hemin is a promising approach in the treatment of CP-induced nephrotoxicity. However, further preclinical studies are warranted to test effectiveness of CP/hemin on the outcome of tumor chemotherapy.