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Cadmium is among the toxic and hazardous metal widely dispersed in the environment in high levels. Current studies have provided new insights into antioxidant properties of bioflavonoid which have emerged as probable therapeutic and nutraceutical agents. The present study is geared to investigate the possible role of Cymbopogon schoenanthus (L.) Spreng. (or Ethkher) on heavy metal cadmium (Cd) induced oxidative stress in mice. Mice were randomly divided into four groups and treated for 15 days as follows: group 1: normal control-treated (saline); group 2: Ethkher leaves extract-treated (100 mg/kg); group 3: cadmium chloride (CdCl2) treated; group 4: CdCl2 plus Ethkher leaves extract. The results showed a significant reduction in hemoglobin, RBC and hematocrit in cadmium-treated mice as compared to control. Exposure to Cd caused a significant increase in the number of white blood cells (P

Posttraumatic stress disorder (PTSD) after the pandemic has emerged as a major neuropsychiatric component of post-acute COVID-19 syndrome, yet the current pharmacotherapy for PTSD is limited. The use of adrenergic drugs to treat PTSD has been suggested; however, it is hindered by conflicting clinical results and a lack of mechanistic understanding of drug actions. Our studies, using both genetically modified mice and human induced pluripotent stem cell-derived neurons, reveal a novel α

Conservation and assessment of bio-resources is a challenging task. With the rapid advancement of applied molecular biology techniques and bioinformatics, DNA barcoding and molecular phylogeny studies have gained momentum in the past decade. This chapter gives a brief description of all the chapters in this book—DNA Barcoding and Molecular Phylogeny. It includes some important case studies along with DNA barcoding information in relation to invasive alien species, forensic botany, infection management, plant animal interactions, fishery management, DNA database management, etc. Other topics include DNA barcoding and molecular phylogeny in microbes, aquatic plants, medicinal plants, red alga, ichthyoplankton, rays, fishes, reptiles, birds, and ruminant mammals. The concept of R as a bioinformatics tool in DNA barcoding is also discussed.

Tacrolimus (TAC) is used sporadically as an immunosuppressive agent for organ transplantation, but its clinical used is limited due to its marked nephrotoxicity. Ocimum basilicum L. (Lamiaceae) (OB) had been shown to possess antioxidant, anti-inflammatory and nephroprotective activity, and effective at improving renal inflammation and glomerular. In our study, we aim to evaluate the efficacy of the OB against TAC-induced mitochondrial nephrotoxicity in CD1 mice. Mice were randomly divided into four groups. Group 1 (control group); administered orally with normal saline (1 mL/kg) for two weeks; Group 2 (OB extract treated-group) (500 mg/kg b.wt) gavaged once/day for two weeks; Group 3 (TAC-treated group) (3 mg/kg b.wt, administered ip once a day for two weeks); and Group 4; (TAC plus OB extract treated-group). Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. The OB extract was high in phenolic content (50.3 mg/g of gallic acid equivalent), total flavonoids (14.5 mg/g CE equivalent). The potential antioxidant efficacy of the extract (IC50) was 24.5 μg/mL. OB pretreatment significantly improved the TAC-induced changes in biochemical markers of nephrotoxicity for instance blood urea nitrogen (BUN), creatinine, total protein, and albumin (P

Artemisia judaica L. (Compositae) are shrubby herbs growing wildly in Tabuk region and distributed in the desert regions. This region is characterized by extremely variable environmental conditions where the temperature varies from extreme low to extreme high. These temperature regimes have a profound effect on morphology, growth physiology and biochemistry of the plants. The plant samples were collected from Tabuk–Jordan road (760 m above sea level) in the month of January, April, July and October 2013 to evaluate the effect of temperature dynamics on A. judaica L. in four different seasons. Physiological, biochemical alterations and heat shock proteins (HSPs) were studied during these seasons in order to evaluate the environmental adaptation and stress tolerance in response to temperature variations. Plant growth parameters showed a significant increase in height, fresh and dry matter accumulation, total chlorophyll, nitrogen, phosphorus, potassium, artemisinin and leaf relative water contents investigated in the month of April and October. Growth of plant was suppressed and an active role of carbonic anhydrase (CA), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) was observed to cope with the extreme low temperature in January and extreme high temperature in July 2013. However, the plants collected in October and April did not show a statistical difference. Inductions in the expression of HSP90 were recorded in all the plants collected during April and October 2013 with no statistically significant difference. Therefore, based on the results it is recommended that during April and October the environmental conditions are best suitable for growth, development and medicinal use of Artemisia. Keywords: Antioxidants, Climate change, Growth, Heat shock proteins, Medicinal plants

Exposure to natural and man-made environmental toxins concurrently can pose a greater threat to multiple organs. In the present work, we investigated interactions between deltamethrin (DM) and cadmium (Cd), whose mechanisms of action in humans are poorly understood. Albino mice were randomly divided into four groups, each containing six mice: saline as control, DM-treated, cadmium chloride (CdCl2)-treated, and CdCl2 plus DM treated. After 2 weeks of treatment biochemical and hematological effects, total leukocyte count (TLC), differential leukocyte count, humoral-mediated immune responses, and histopathological studies were conducted. Mice exposed to DM and Cd showed a significant increase in aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Also, DM and Cd administration resulted in suppression of humoral immunity, erythrocyte count, hemoglobin, hematocrit, and TLC. Histopathological evidence revealed hepatic damage, supporting the AST and ALT findings. Cd and DM exhibited an additive type of toxicity. It could be concluded that these toxins either target different cellular pathways, or the individual amounts used in this study were not enough to saturate the toxicological target, thus producing additive effects.

Objective To investigate the effectiveness of slow release formulations of Bacillus thuringiensis israelensis (AM 65-52) (B. thuringiensis israelensis) and spinosyns against the West Nile vector Culex pipiens (Cx. pipiens) in Saudi Arabia. Methods We tested slow release insecticide formulations of Natular DT, Tap 60 and VectoBac granule against II instars of Cx. pipiens larvae in 50 L laboratory arenas. Results Slow release formulations of B. thuringiensis israelensis and spinosyns gave continuous control against Cx. pipiens for several weeks. Natular DT was more effective over Tap 60 and VectoBac granule of about 1.3 and 5.8 times, respectively. Variations in the durations of effective control among the tested slow release formulations may reflect differences in their active ingredients and the mode of action. Conclusions Our results highlighted the effectiveness of B. thuringiensis israelensis and spinosyns against an important West Nile vector, providing baseline data to develop eco-friendly mosquito control programs in Saudi Arabia.

Since the original discovery of stem cells, a new era of promising results has emerged in the clinical application of stem cells for the treatment of several important diseases, including cancer and autoimmune diseases. The plentiful research on stem cells during the past decades has provided significant information on the developmental, morphological, and physiological processes that govern tissue and organ formation, maintenance, and regeneration; cellular differentiation; molecular processes; and tissue homeostasis. In this review, we present the history of the use of stem cells in different clinical applications. Furthermore, we discuss the various therapeutic options for stem cells in cancer, followed by the role of stem cells in the treatment of autoimmune disorders. Additionally, we highlight the risks of and obstacles to the application of stem cells in clinical practice. Ultimately, we show future perspectives in stem cell use, with an aim to improve the clinical usefulness of stem cells.

Eutrophication is posing a threat to the coastal marine ecosystems. The consequence of anthropogenic induced eutrophication of waters has resulted in severe deterioration of surface waters. In this research a preliminary data was collected on eutrophication by environmental monitoring on some selected coastal areas of the Red Sea near Tabuk, Saudi Arabia. Sampling sites were selected from Haql, Sharmaa and Duba (five for each station) and water samples collected in four different seasons (Oct 2013, Jan 2014, April 2014 and July 2014) to study seasonal dynamics of water quality parameters (especially in reference to the trophic status of water). Only one coastal site from each station was found with some eutrophic characteristics. Water samples collected from these eutrophic sites were more alkaline, turbid, with higher nutrient and low dissolved oxygen contents as compared to other sampling sites. Dynamics in relative densities of coastal flora and fauna were also found to be related with coastal water quality. Human settlements, fish markets, boating clubs and tourisms near these coastal areas of the Red Sea were observed as the primary causes of nutrient loading; run-offs during rains carrying nutrients also aggravate the problem. The results of this study may help in estimating the intensity of the problem and as a forecast for time frame to take an action for the conservation of affected coastal marine ecosystems and restoration of degraded coastal areas of the Red Sea.

Objective: To review and analyze the pattern of breast cancer (BC) in the Kingdom of Saudi Arabia (KSA). Methods: A retrospective review of BC among female patients was conducted at the Faculty of Sciences, Department of Biology, University of Tabuk, Tabuk, Saudi Arabia from January 1990 to December 2014. This report contains information obtained from the Saudi Cancer Registry and from King Faisal Specialist Hospital and Research Center. Results: The number of women with BC increased steadily from 1990-2010. On the basis of the number of cases, the percentage distribution of BC appears to be increasing. There were 1152 female BC cases in 2008 in comparison with 1308 in 2009, and 1473 in 2010. Breast cancer ranked first among females accounting for 27.4% of all newly diagnosed female cancers (5378) in the year 2010. The average age at the diagnosis of BC was 48; weighted average was 49.8, and range 43-52. Conclusion: Among Saudi patients, there was a significant increase in the number of cases of BC, which occurs at an earlier age than in western countries. Continued vigilance, mammographic screening, and patient education are needed to establish early diagnosis and perform optimal treatment. Saudi Med J 2015; Vol. 36 (10): 1176-1180 doi: 10.15537/smj.2015.10.12268

The phytochemical, antioxidant and mineral composition of hydroalcoholic extract of leaves of Cichorium intybus L., was determined. The leaves were found to possess comparatively higher values of total flavonoids, total phenolic acids. The phytochemical screening confirmed the presence of tannins, saponins, flavonoids, in the leaves of the plant. The leaf extract was found to show comparatively low value of IC50 for 2,2-diphenyl-1-picrylhydrazyl (DPPH) inhibition. The IC50 value of chicory leaves extract was found to be 67.2±2.6μg/ml. The extracts were found to contain high amount of mineral elements especially Mg and Zn. Due to good phytochemical and antioxidant composition, C. intybus L., leaves would be an important candidate in pharmaceutical formulations and play an important role in improving the human health by participating in the antioxidant defense system against free radical generation.

Background: Tacrolimus is a known immunosuppressive drug used widely for organ transplantation, but its nephrotoxicity mechanism is still unclear. Objectives: The present study investigates the protective efficacy of Bacopa monnieri (BM), against tacrolimus-induced nephrotoxicity in rats. Materials and Methods: Group 1 (control group); administered orally with normal saline for 30 days; Group 2 (BM extract treated group); Group 3 (tacrolimus-treated group); and Group 4; (tacrolimus plus BM extract treated group). Tacrolimus-treated rats received 1 mg/kg body weight of tacrolimus intraperitoneally for 30 days, and BM-pretreated rats were administered with the dose of 200 mg/kg orally by gavage once a day for 30 days. Results: Tacrolimus-induced nephrotoxicity was assessed biochemically and histopathologically. Pretreatment with BM has shown to possess a significant protective effect against tacrolimus-induced kidney functions regarding urea, creatinine, and albumin levels, respectively. The creatinine, mitochondrial lipid peroxidation (thiobarbituric acid reactive substances), and protein carbonyl levels were significantly increased dramatically, and however, the total proteins, albumin, glutathione, superoxide dismutase, and glutathione peroxidase were decreased when pretreated with tacrolimus. The nephroprotective efficacy of the BM extract was further evident by histopathological analysis and DNA fragmentation. Conclusion: The outcome of this study indicates that BM extracts exerted protection against tacrolimus-induced kidney toxicity. Abbreviations Used: ANOVA: Analysis of variance, BM: Bacopa monnieri, BUN: Blood urea nitrogen, DNPH: Dinitrophenylhydrazine, DPPH: 2,2-diphenyl-1-picrylhydrazyl, DSR: Deanship of Scientific Research, EOBPV: Egyptian Organization for Biological Products and Vaccines, GPx: Glutathione peroxidase, GSH: Glutathione, H and E: Hematoxylin and eosin, H2O2: Hydrogenperoxide, IAEC: Institutional Animals Ethics Committee, IC: Inhibitory concentration, Ip: Intraperitoneal, mLPO: Mitochondrial lipid peroxidation, Mn-SOD: Mn-superoxide dismutase, PC: Protein carbonyl, ROS: Reactive oxygen species.

[No Abstract Available] Saudi Med J 2016; Vol. 37 (3): 329. doi: 10.15537/smj.2016.3.14677 How to cite this article Dastgiri S, Saggu S. Frequency, incidence, and prevalence. Saudi Med J 2016; 37: 329.

The World registry of marine species as of May, 2015 show 229,409 accepted species; of which 220,461 checked (96 %) 421,632 species names including synonyms 527,721 taxon names. Therefore there was a desperate need for developing new molecular method for clarifying obscurities in customary taxonomy. As most of the organisms in marine habitat are microscopic, sample size is large, and most of all the sample preservation is a tricky and expertise requiring job, marine taxonomic identification progress has been very slow. Therefore there was an urgent need of “fast, simple, reliable and inexpensive” method for identification of marine diversity and the answer came as a technique known as “DNA Barcoding”. DNA barcoding has emerged as an ideal technique for taxonomic identification of marine taxa, as morphological characters are less reliable and often lead to cryptic species overlapping. Combining genomic study with DNA barcode can be a very effective solution. With all the advantages and limitations there is a strong implementation of DNA barcode on large scale barcode campaigns that will provide enormous amount of data for proper marine taxonomy especially in marine invertebrates.

Objective To investigate the susceptibility to some conventional and non-conventional insecticides in laboratory and field larval populations of the West Nile vector Culex pipiens L. (Cx. pipiens), the dominant species in Jeddah Province, Saudi Arabia. Methods The tested conventional insecticides were Actikil and Pesgard, while the non-conventional ones were Bacilod, Dudim and Baycidal. Probit analysis and photomicroscopical observations were carried out to shed light on acute toxicity in laboratory and field Cx. pipiens strains. Results Cx. pipiens were more susceptible to Pesgard (LC50: 0.045 and 0.032 mg/L) than Actikil (0.052 and 0.038 mg/L) and Bacilod (0.129 and 0.104 mg/L), for the field and laboratory strains, respectively. Results showed that treatments with the chitin synthesis inhibitor Dudim and Baycidal evoked morphological effects similar to those induced by other insect growth regulators. According to IC50 values obtained (concentration which to inhibit the emergence of 50% of mosquito adults), the compound Dudim (0.000 3 and 0.000 1 mg/L) was more effective against Cx. pipiens L. mosquitoes than Baycidal (0.000 4 and 0.000 3 mg/L) for both the field and laboratory strains, respectively. Conclusions Our results provide baseline data to enhance control programs and orient public health decisions on the selection of pesticides against mosquito vectors in Saudi Arabia.

Major part of our planet includes the marine habitat which faces severe threat due to overexploitation of its bio resources. Assessment of biodiversity in the massive and diverse marine ecosystem is a challenging task. In this introductory chapter, we give a brief description of the marine habitat and types of marine organisms, followed by the concept of DNA barcoding. We also describe the applications and different initiatives of DNA barcoding in the marine ecosystem. A brief account of DNA barcoding in marine fungi, different groups of animals and plants is also elucidated. This chapter gives a bird’s eye view on the DNA barcoding in the marine perspective.

Consumers of today have more apprehension on food safety ever before and high value markets such as EU and USA market are place much attention on it. Quality of food is a very important aspect of human life and people become more and more anxious about nutrition, food safety and environmental issues that determine their acceptance of food products. Food traceability is a central issue for the identification of improper labeling of processed food and feed and there are rules aimed to protect consumers and producers against fraudulent but the tools available are not always appropriate. Recently, DNA barcoding has gained support as a rapid, cost-effective and broadly applicable molecular diagnostic technique for seafood authentication. DNA barcoding methodologies are progressively more applied not only for scientific purposes but also for diverse real-life uses. The present chapter brings out a comprehensive review on the seafood authentication and fraud. Developing country markets are placing poor attention on food safety and sanitation measures and rising levels of market information, education and awareness programmes will help to minimize the gap.

Information science has been applied to manage the information generated in molecular biology to produce the field called Bioinformatics. Application of bioinformatics in several ways is an integral part of DNA barcode research. Since the origin of the DNA barcode concept, three major criteria were set up to test the efficiency of barcode regions. These are (i) Universal Primers to amplify the barcode region (ii) Calculation of Barcode gap (intra and interspecies distance) (iii) Species resolution power. For evaluation of these criteria, DNA barcode community is applying bioinformatics tools and algorithms in primer design, distance calculation, phylogenetic analysis, etc. DNA Barcoding produces a huge amount of Cytochrome c oxidase subunit I (COI) sequences information for species identification from animal kingdom of marine biodiversity. Similarly, Consortium of Barcode of Life (CBOL) plant group proposed plastid genes rbcL and matK either singly or in combination as the standard DNA barcode for plants (CBOL Plant Working Group 2009). ITS of the nuclear ribosomal RNA standardized as the universal barcode marker for fungi. Bioinformatics play a major role in storing of DNA barcode information, and it is easy to retrieve from the database. Software-based sequence quality assurance is main starting and check point for the production of barcode sequences. In this chapter, we discussed different tools and methods of bioinformatics and their proper utilization.

Aqueous and 70% ethanol extracts of seabuckthorn (Hippophae rhamnoides L., Elaeagnaceae) dry leaves were examined in rats for their dose dependent effect on active avoidance learning, if any. Avoidance learning was studied during endurance performance in multiple stressful environments consisting of light, noise and electric shock (10 mV) by using Runimex, a circular runway animal model. Neither of the evaluated extracts showed activity in rats to enhance cognitive functions with reference to avoidance learning during exposure to stressful conditions of multiple stressors. But both extracts were found to possess physical performance enhancing activity during the studied stressful conditions.

Evidence suggests that GABA might mediate the inhibitory influence of centrifugal inputs on taste-evoked responses in the parabrachial nucleus (PBN). Previous studies show that activation of the gustatory cortex (GC), bed nucleus of the stria terminalis (BNST), central nucleus of the amygdala (CeA), and lateral hypothalamus (LH) inhibits PBN taste responses, GABAergic neurons are present in these forebrain regions, and GABA reduces the input resistance of PBN neurons. The present study investigated the expression of glutamic acid decarboxylase immunoreactivity (GAD_67 ir) in GC, BNST, CeA, and LH neurons that project to the PBN in rats. After anesthesia (50 mg/kg ip Nembutal), injections of the retrograde tracer Fluorogold (FG) were made in the physiologically defined gustatory PBN. Brain tissue containing the above forebrain structures was processed and examined for FG and GAD_67 ir. Similar to previous studies, each forebrain site contained retrogradely labeled neurons. Our results suggest further that the major source of input to the PBN taste region is the CeA (608 total cells) followed by GC (257 cells), LH (106 cells), and BNST (92 cells). This suggests a differential contribution to centrifugal control of PBN taste processing. We further show that despite the presence of GAD_67 neurons in each forebrain area, colocalization was extremely rare, occurring only in 3 out of 1,063 FG-labeled cells. If we assume that the influence of centrifugal input is mediated by direct projections to the gustatory region of the PBN, then GABAergic forebrain neurons apparently are not part of this descending pathway.

The present study was carried out to investigate mechanism of adaptogenic activity of seabuckthorn dry leaves aqueous lyophilized extract, administered in rats at a dose of 100 mg/kg body weight prior to cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) exposure up to fall of T(rec) 23 degrees C and recovery (T(rec) 37 degrees C) from C-H-R induced hypothermia. The effect of extract treatment was studied on key metabolic regulatory enzymes in blood, liver and muscle and tissue glycogen in rats on attaining T(rec) 23 degrees C and post stress recovery of T(rec) 37 degrees C. In control rats during C-H-R exposure on attaining T(rec) 23 degrees C there was significant decrease in enzyme activities of blood hexokinase (HK), citrate synthase (CS) and glucose-6-phosphate dehydrogenase (G-6-PD); liver CS; and in muscle glycogen, and CS and G-6-PD activities. In control rats on recovery of T(rec) 37 degrees C there was also a significant decrease in liver and muscle glycogen levels along with decreased enzyme activities of blood G-6-PD; liver CS; and liver and muscle G-6-PD. This suggested that during severe stressful exposure to C-H-R and post stress recovery the aerobic metabolism as well as hexose monophosphate (HMP) pathway is suppressed. The single and five doses extract treatment restricted the decrease or better maintained tissue glycogen and enzyme activities, viz. HK, phosphofructokinase (PFK), CS and G-6-PD, in blood, liver and muscle, during C-H-R exposure (T(rec) 23 degrees C) and recovery of T(rec) 37 degrees C. The results suggest that seabuckthorn extract treatment caused a trend for shifting anaerobic metabolism to aerobic during C-H-R exposure and post stress recovery.

Artemisia judaica L. (Compositae) are shrubby herbs growing wildly in Tabuk region and distributed in the desert regions. This region is characterized by extremely variable environmental conditions where the temperature varies from extreme low to extreme high. These temperature regimes have a profound effect on morphology, growth physiology and biochemistry of the plants. The plant samples were collected from Tabuk–Jordan road (760 m above sea level) in the month of January, April, July and October 2013 to evaluate the effect of temperature dynamics on A. judaica L. in four different seasons. Physiological, biochemical alterations and heat shock proteins (HSPs) were studied during these seasons in order to evaluate the environmental adaptation and stress tolerance in response to temperature variations. Plant growth parameters showed a significant increase in height, fresh and dry matter accumulation, total chlorophyll, nitrogen, phosphorus, potassium, artemisinin and leaf relative water contents investigated in the month of April and October. Growth of plant was suppressed and an active role of carbonic anhydrase (CA), catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD) was observed to cope with the extreme low temperature in January and extreme high temperature in July 2013. However, the plants collected in October and April did not show a statistical difference. Inductions in the expression of HSP90 were recorded in all the plants collected during April and October 2013 with no statistically significant difference. Therefore, based on the results it is recommended that during April and October the environmental conditions are best suitable for growth, development and medicinal use of Artemisia.

A wide range of anthropogenic activities cause physiochemical changes in the nature of soil. This leads to the contamination of environment. There are many methods employed to clean up environment from these contaminants, but most of them are costly and ineffective to provide proper results. Chemical methods employed act with complicated mechanism and lots of cost input. Phytoremediation is a technology that acts with deployment of green plants, for removal of toxic metals from the polluted environment. Phytoremediation is a cost-effective technique through which clean-up of contaminated soil loaded with high heavy metals is performed by weeds and small herbal plants. Phytoremediation has become a successful technology for hyperaccumulation of heavy metals; arsenic, lead, mercury, copper, chromium, nickel etc., by weeds. Weeds have intrinsic capacity to accumulate metals into their shoots and root and further to form phytochelates and stabilize ions. This accumulation activity of these weeds along with stable compound formation acts as a boon for phytoremediation technology.

In the present study, oral supplementation ofl-arginine in rats was evaluated for its anti-stress and adaptogenic activity using the cold (5°C)–hypoxia (428 mmHg)–restraint (C-H-R) animal model. A dose-dependent study ofl-arginine was carried out at doses of 12.5, 25.0, 50.0, 100.0, 200.0 and 500.0 mg/kg body weight, administered orally 30 min prior to C-H-R exposure. The time taken by the rat to attain a rectal temperature of 23°C (Trec 23°C) during C-H-R exposure and its recovery toTrec 37°C at normal atmospheric pressure and 32 ± 1°C were used as biomarkers of anti-stress and adaptogenic activity. Biochemical parameters related to lipid peroxidation, anti-oxidants, cell membrane permeability, nitric oxide and stress, with and without administration of the least effectivel-arginine dose, were measured in rats on attainingTrec 23°C andTrec 37°C. The least effective adaptogenic dose ofl-arginine was 100.0 mg/kg body weight. The C-H-R exposure of control rats, on attainingTrec 23°C, resulted in a significant increase in plasma malondialdehyde (MDA), blood lactate dehydrogenase (LDH) and a decrease in blood catalase (CAT) and plasma testosterone levels. On recovery (Trec 37°C) of control rats, there was a further decrease in CAT and plasma testosterone, and an increase in LDH.l-Arginine supplementation resulted in a significant decrease in plasma MDA, an increase in blood superoxide dismutase (SOD), CAT levels maintained at control values and a lower increase in LDH compared with controls (45.3 versus 58.5% and 21.5 versus 105.2%) on attainingTrec 23°C during C-H-R exposure and on recovery toTrec 37°C. The results suggested thatl-arginine possesses potent anti-stress activity during C-H-R exposure and recovery from C-H-R-induced hypothermia.

The current study was carried out to elucidate the modulating effect of chicory (Cichorium intybus L.) fruit extract (CFR) against 4-tert-OP induced oxidative stress and hepatotoxicity in male rats. Rats were divided into four groups and treated for 8 weeks as follow: group 1: normal control-treated (saline); group 2: chicory fruit extract-treated (100 mg/kg); group 3: 4-tert-OP treated; group 4: 4-tert-OP plus chicory fruit extract. The obtained results revealed that rats which received 4-tert-OP showed a significant increase in liver TBARS and bilirubin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGTP) activities. While a significant decrease in the levels of GSH, SOD, catalase recorded. On the other hand, CFR extract succeeded to modulate these observed abnormalities resulting from 4-tert-OP as indicated by the reduction of TBARS and the pronounced improvement of the investigated biochemical and antioxidant parameters. Histopathological evidence, together with observed PCNA and DNA fragmentation, supported the detrimental effect of 4-tert-OP and the ameliorating effect of CFR extract on liver toxicity. So, it could be concluded that chicory has a promising role and it worth to be considered as a natural substance for ameliorating the oxidative stress and hepatic injury induced by 4-tert-OP compound.

Objective Acetaminophen (APAP) is a substance that harms human health by stimulating free radical production. This study investigated the ability of Trifolium alexandrinum root (TAR) extract to reduce the hepatotoxicity induced by APAP in rats. Methods Animals were classified into four groups and treated for 6 weeks. Group 1: normal control-treated (saline); Group 2: TAR extract-treated (100 mg/kg); Group 3: APAP-treated; Group 4: APAP plus TAR extract. Results APAP significantly elevated AST (aspartate amino transferase), ALT (amino alanine transferase), ALP (alkaline phosphatase), GGTP (gamma glutamyl transpeptidase), bilirubin, and malondialdehyde with a significant decrease in glutathione, superoxide dismutase, glutathione peroxidase, catalase, and glutathione S-transferase compared with the control group. Administration of TAR extract combined with APAP improved the liver damage induced by APAP. Histopathological evidence, together with observed DNA fragmentation, supported the detrimental effect of APAP and the ameliorating effect of TAR extract on liver toxicity. Conclusion TAR extract has beneficial properties and can reduce the liver damage and toxicity induced by APAP. Discussion Free radical mediated processes have been implicated in the pathogenesis of many diseases. The protective effect of TAR root extract on APAP-induced hepatotoxicity in rats appears to be related to inhibition of lipid peroxidation and enhancement of antioxidant enzyme levels, in addition to a free radical scavenging action.

Behavioral genetic studies of humans have associated variation in the DTNBP1 gene with schizophrenia and its cognitive deficit phenotypes. The protein encoded by DTNBP1, dysbindin-1, is expressed in forebrain neurons where it interacts with proteins mediating vesicular trafficking and exocytosis. It has been shown that loss of dysbindin-1 results in a decrease in glutamate release in the prefrontal cortex; however the mechanisms underlying this decrease are not fully understood. In order to investigate this question, we evaluated dysbindin-1 null mutant mice, using electrophysiological recordings of prefrontal cortical neurons, imaging studies of vesicles, calcium dynamics and Western blot measures of synaptic proteins and Ca(2+) channels. Dysbindin-1 null mice showed a decrease in the ready releasable pool of synaptic vesicles, decreases in quantal size, decreases in the probability of release and deficits in the rate of endo- and exocytosis compared with wild-type controls. Moreover, the dysbindin-1 null mice show decreases in the [Ca(2+)]i,expression of L- and N-type Ca(2+)channels and several proteins involved in synaptic vesicle trafficking and priming. Our results provide new insights into the mechanisms of action of dysbindin-1.

In photodynamic therapy (PDT), light activates a photosensitizer added to a tissue, resulting in singlet oxygen formation and cell death. The photosensitizer phthalocyanine 4 (Pc 4) localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. The aim of this study was to determine how lysosomes contribute to PDT-induced cell killing by mitochondria-targeted photosensitizers such as Pc 4. We monitored cell killing of A431 cells after Pc 4-PDT in the presence and absence of bafilomycin, an inhibitor of the vacuolar proton pump of lysosomes and endosomes. Bafilomycin was not toxic by itself, but greatly enhanced Pc 4-PDT-induced cell killing. To investigate whether iron loading of lysosomes affects bafilomycin-induced killing, cells were incubated with ammonium ferric citrate (30 μM) for 30 h prior to PDT. Ammonium ferric citrate enhanced Pc 4 plus bafilomycin-induced cell killing without having toxicity by itself. Iron chelators (desferrioxamine and starch-desferrioxamine) and the inhibitor of the mitochondrial calcium (and ferrous iron) uniporter, Ru360, protected against Pc 4 plus bafilomycin toxicity. These results support the conclusion that chelatable iron stored in the lysosomes enhances the efficacy of bafilomycin-mediated PDT and that lysosomal disruption augments PDT with Pc 4.

Several forebrain areas have been shown to project to the parabrachial nucleus (PBN) and exert inhibitory and excitatory influences on taste processing. The neurochemicals by which descending forebrain inputs modulate neural taste-evoked responses remain to be established. This study investigated the existence of somatostatin (SS) and corticotrophin releasing factor (CRF) in forebrain neurons that project to caudal regions of the PBN responsive to chemical stimulation of the anterior tongue as well as more rostral unresponsive regions. Retrograde tracer was iontophoretically or pressure ejected from glass micropipettes, and seven days later the animals were euthanized for subsequent immunohistochemical processing for co-localization of tracer with SS and CRF in tissue sections containing the lateral hypothalamus (LH), central nucleus of the amygdala (CeA), bed nucleus of the stria terminalis (BNST), and insular cortex (IC). In each forebrain site, robust labeling of cells with distinguishable nuclei and short processes was observed for SS and CRF. The results indicate that CRF neurons in each forebrain site send projections throughout the rostral caudal extent of the PBN with a greater percentage terminating in regions rostral to the anterior tongue responsive area. For SS, the percentage of double-labeled neurons was more forebrain site specific in that only BNST and CeA exhibited significant numbers of double labeled neurons. Few retrogradely labeled cells in LH co-expressed SS, while no double labeled cells were observed in IC. Again, tracer injections into rostral PBN resulted in a greater percentage of double labeled neurons in BNST and CeA compared to caudal injections. The present results suggest that some sources of descending forebrain input might utilize somatostatin and/or CRF to exert a broad influence on sensory information processing in the PBN.

In photodynamic therapy (PDT), visible light activates a photosensitizing drug added to a tissue, resulting in singlet oxygen formation and cell death. Assessed by confocal microscopy, the photosensitizer phthalocyanine 4 (Pc 4) localizes primarily to mitochondrial membranes in cancer cells, resulting in mitochondria-mediated cell death. A Pc 4 derivative, Pc 181, accumulates into lysosomes. In comparison to Pc 4, Pc 181 was a more effective photosensitizer promoting killing cancer cells after PDT. The mode of cell death after Pc 181-PDT is predominantly apoptosis, and pancaspase and caspase-3 inhibitors prevent onset of the cell death. To assess further how lysosomes contribute to PDT, we monitored cell killing of A431cells after PDT in the presence and absence of bafilomycin, an inhibitor of the acidic vacuolar proton pump that collapses the pH gradient of the lysosomal/endosomal compartment. Bafilomycin by itself did not induce toxicity but greatly enhanced Pc 4-PDT-induced cell killing. In comparison to Pc 4, less enhancement of cell killing by bafilomycin occurred after Pc 181-PDT at photosensitizer doses producing equivalent cell killing in the absence of bafilomycin. These results indicate that lysosomal disruption can augment PDT with Pc 4, which targets predominantly mitochondria, but less so after PDT with Pc 181, since Pc 181 already targets lysosomes.

This study was carried out to examine the antioxidative potential, if any, of seabuckthorn leaf aqueous extract, administered orally in rats at a dose of 100 mg kg−1 both in single and five doses, 30 min before cold (5°C)–hypoxia (428 mm Hg)–restraint (C-H-R) exposure. The effect of the extract was studied on lipid peroxidation and antioxidant parameters in liver and gastrocnemius muscle of rats on attaining the rectal temperature (Trec) of 23°C during C-H-R exposure and after recovery (Trec37°C) from C-H-R-induced hypothermia. In untreated rats exposed to C-H-R, there was a significant increase in malondialdehyde (MDA) levels in liver and muscle along with decreased activity of catalase (CAT) and glutathione-S-transferase (GST) in liver and muscle. Single- and five-dose extract treatment restricted the increase in liver and muscle MDA levels and five doses of extract treatment further improved the levels of liver antioxidants, viz. reduced glutathione (GSH), on recovery of Trec37°C, increased superoxide dismutase (SOD) during exposure and recovery, normalized CAT activity in liver during C-H-R exposure and an increase on recovery of Trec37°C. The decreasing pattern of liver and muscle GST levels both in single-dose and five-dose extract treated rats was similar to that in untreated rats. Results suggested that supplementation with seabuckthorn extract helps to reduce oxidative stress in liver and muscle of rats during C-H-R exposure and post-stress recovery.