8^th World Congress on Pharmacology and Toxicology July 24-25, 2017 Melbourne, Australia

Objective: Cisplatin is a commonly used antineoplastic agent for the treatment of several solid tumors. Peripheral neuropathy is one of its major side effects. Agmatine has been shown to relieve neuropathic pain in different animal models. Cannabinoids have shown analgesic features in neuropathic pain models. The aim of this study was to investigate the effects of anandamide, a cannabinoid receptor agonist, and agmatine on cisplatin-induced neuropathy. Materials and Methods: Neuropathy was induced in male Wistar rats (250-300 g, n=6) by intraperitoneal injections of cisplatin 3 mg/kg once a week for five consecutive weeks. The development of neuropathy was evaluated using tests for both mechanical allodynia and heat-hypo/hyperalgesia. After 5 weeks of treatments, cardiac perfusion with paraformaldehyde was performed and dorsal root ganglion (DRG) neurons were collected for further electron microscopic evaluation. Single dose of agmatine (100 mg/kg) or anandamide (1 mg/kg) was given intraperitoneally. The development of neuropathy was evaluated using tests for both mechanical allodynia and heat-hypo/hyperalgesia. Spontaneous locomotor activity, rectal temperature, antinociception and catalepsy were evaluated for cannabinoid tetrad. After 5 weeks of treatments, cardiac perfusion with paraformaldehyde was performed and dorsal root ganglion (DRG) neurons were collected for further electron microscopic evaluation. Results: Cisplatin treatment induced mechanical allodynia and thermal hyperalgesia. Single dose of agmatine significantly attenuated cisplatin-induced mechanical allodynia. Conclusions: It seems that agmatine may have antinociceptive activity on cisplatin-induced neuropathy. However, single dose of anandamide did not alleviate cisplatin-induced thermal hyperalgesia. This study was supported by “Eskisehir Osmangazi University Scientific Research Projects Commission”

Prof. Fatma Sultan KILIC has completed her PhD at the age of 31 years from Anadolu University. She has been working as an academic member since 1995. She’s also contunuing her PhD at faculty of education.She has published more than 45 papers in reputed journals and her h-index is 12

Enhancing cholinergic transmission is suggested to improve cognitive functions. We aimed to investigate the effects of galangin, a flavonoid compound that is reported to inhibit acethylcholinesterase enzyme,on mecamylamine-induced spatial memory impairments in rats. Methods: Morris water maze test was used to investigate the spatial memory. Galangin 50 and 100mg/kg was administered acutely 30 minutes before the impairment of spatial memory by a nicotinic receptor antagonist mecamylamine injection. Donepezil 1mg/kg used as a reference drug. Distance to platform and time spent in escape platform quadrant were recorded and analyzed with Ethovision XT version 9.0 (Noldus, Wageningen, Netherlands). Results were statistically analyzed with one-way ANOVA. Results: Mecamylamine significantly increased the distance to platform and decreased the time spent in the escape platform quadrant compared to control group. Galangin 100 but not 50mg/kg significantly decreased the distance to platform and increased the time spent in the escape platform quadrant compared to mecamylamine group comparable to donepezil 1mg/kg. Conclusion: Galangin 100g/kg may improve memory comparable to donepezil and nicotinic receptors may be involved in this effect. This study is a part of an ongoing project which is supported by the Commission of Scientific Researches Projects in Eskisehir Osmangazi University (Project number : 2013-93)

Guner Ulak has completed her PhD from Dicle University School of Medicine and postdoctoral studies from Kocaeli University School of Medicine. She is the director of Pharmacology Department, Medical Faculty, Kocaeli University,Turkey. She has published more than 70 papers in English, more than 45 in Turkisch and she has many more poster presentations.

Phosphodiesterases (PDE) are enzymes that hydrolyze cAMP and/or cGMP throughout the body, including the brain. Preventing the breakdown of cAMP by PDE inhibitors promotes memory. PDE inhibitors present a novel therapeutic approach with which to arrest cognitive decline or possibly reverse the decline with cognition enhancement. The aim of this study was to investigate effects of BAY 60-7550, a PDE2 inhibitor; sildenafil, a PDE5 inhibitor and PF-04447943, a PDE9 inhibitor on emotional memory in naive mice using passive avoidance (PA) test. Mice were trained in a one trial step-through PA apparatus for evaluating emotional memory where decrease in retention latency indicate an impairment of memory. BAY60-7550 (1 and 3 mg/kg), sildenafil (3 and 10 mg/kg) or PF-04447943 (1 and 3 mg/kg) (n= 12-15 per group) was administered intraperitoneally 30, 60 and 60 min respectively before the acquisition session of PA test. One way Anova post hoc Tukey’s test was used for the statistical analysis of the data. The results of this study revealed that there was significant difference between the first day latency of the animals. Drug treatment, significantly prolonged the retention latency of PA test in the second day compared to control group (3mg/kg BAY 60-7550 vs control p<0.05; 10 mg/kg sildenafil vs control p<0.05; 3 mg/kg PF-04447943 vs control p<0.01). Our results confirm that BAY 60-7550, sildenafil and PF-04447943 enhance emotional memory of mice in the PA test . Further studies and different cognition models are needed to support our results and enlighten whether these effects are test dependent or not.

Füruzan YILDIZ AKAR has completed her PhD and postdoctoral studies from Kocaeli University School of Medicine. F. Y. Akar currently works as an associate professor at the Kocaeli University School of Medicine. She has published more than 50 papers in English and she has many more poster presentations.

Phosphodiesterases (PDEs) are enzymes that hydrolyze cyclic AMP (cAMP) and/or cyclic GMP (cGMP) throughout the body, including the brain. Accumulating evidence indicates that the inhibition of phosphodiesterase (PDE) activity may be a particularly interesting mechanism for memory enhancement. PDE inhibitors present a novel therapeutic approach with which to arrest cognitive decline or to possibly reverse this decline with cognitive enhancement. The aim of this study was to investigate effects of BAY 60-7550, a PDE2 inhibitor and PF-04447943, a PDE9 inhibitor on olfactor memory in naive mice using social transmission of food preference (STFP) test. Hippocampus-dependent non-spatial olfactory memory was studied using the STFP. In the STFP test, the ratio of the weight of the cued food eaten and the total weight of food eaten was used as a measure of food preference. Higher percentage of cued food/total food eaten reflects better performance in olfactory memory. BAY60-7550 (1 and 3 mg/kg) and PF-04447943 (1 and 3 mg/kg) (n= 12 per group) were administered intraperitoneally 30 and 60 min; respectively before the retention session of STFP test. One way Anova post hoc Tukey’s test was used for the statistical analysis of the data. BAY 60-7550, and PF-04447943 significantly increased % cued food/total food eaten compared to the control group. BAY 60-7550, and PF-04447943 also decreased total food consumption compared to the control group but it was not significant. Our results confirm that BAY 60-7550 and PF-04447943 enhance olfactory memory of naive mice in the STFP test .

Li ZHOU has completed her PhD from Beijing Institute of Pharmacology and Toxicology, and postdoctoral studies from Chinese Academy of Medical Sciences. She is the deputy director of National Evaluation Centre for the Toxicology of Fertility Regulating Drug, a laboratory has acquired the GLP certificate of CFDA(China Food And Drug Administration). She has published more than 40 papers in china and abroad reputed journals.

ZishenYutai Pill (ZYP) is one of the most commonly used Chinese medicines in prevention of early pregnancy loss due to threatened and recurrent miscarriage. Although it is widely used, its toxicity during perinatal period has not been well understood. Its main components include Radix Codonopsis, Radix Dipsaci, Polygoni Multiflori, Atractylodes macrocephala, Morinda officinalis, Eucommia Ulmoides, Semen Cuscutae and Radix Rehmanniae Praeparata. In recent years, the research on ZYP has been increased year by year. Previous studies have shown that ZYP combined with phloroglucinolis is significantly effective in the treatment of threatened abortion. Methods: Pregnant rats (F0) were exposed to 6 g/kg, 12 g/kg and 24 g/kg body weight/d of ZYP by intragastric administration from gestation day 15 (GD15) to through parturition and lactation up to weaning, i.e. post-natal day 21 (PND21). Water and propylthiouracil (PTU, 15 mg/kg) were used as the negative control and positive control, respectively. The mating was done between the treatment (ZYP or PTU) group and negative control group when the F1 pups were born 63 days. Results: The reproductive capacity of F0 and F1 generation decreased significantly after PTU exposure (P<0.05); however, the body weight and reproductive ability of F0, the physical development and feed consumption of F1 as well as the reproductive ability and survival rate of F2 rats were not significantly changed in the ZYP group compared with the negative control group (P>0.05). Conclusion: There was no statistically significant evidence of perinatal toxicity under ZYP exposure.

Han Yan is the Quality assurance master of National Evaluation Centre for the Toxicology of Fertility Regulating Drug; a laboratory has acquired the GLP certificate of CFDA (China Food and Drug Administration). She has published more than 20 papers in china and abroad reputed journals.

Apoptosis plays a dominant role in both spontaneous spermatogenesis and germ cell death. This study was aimed to investigate the functions of related genes in testicular germ cell death induced by Hydroxyurea (HU). Method: Wild-type (WT) and FasL transgenic (TG) DBA/C57BL mice were intraperitoneal injected with 400 mg/kg HU. 12 h later, testes were collected. Histomorphology of testis was observed by stained with Periodic Acid Schiff (PAS).Apoptosis was assessed by TUNEL assay. mRNA and protein levels of related genes was evaluated by quantitative RT-PCR and Western blot, respectively. Results: The 2×2 factorial design comparative experiments between WT and TG mice showed that the TG mice exhibited a higher basal apoptotic index. The basal mRNA levels of Fas and FasL and protein levels of Fas, FasL, Caspase-3, Caspase-8 and Caspase-9 in TG mice were also higher than that in WT mice. 12 h after injection of HU, the testicular tubules exhibited no significantly morphological changes but remarkably increased apoptosis index in both WT and TG mice, with the latter having the higher amplitude. Although HU up-regulated the mRNA of apoptosis related genes such as Fas and FasL in both TG and WT mice, the increased amplitude were more obvious in TG mice. By Western blot analysis, apoptosis related proteins Fas, FasL Caspase-3, Caspase- 8 and Caspase-9 were significantly increased in both WT and TG mice, with TG mice exhibiting a greater up-regulation. Conclusion: Germ cell apoptosis induced by HU treatment may be related to the FasL mediated signal transduction pathway.

Zu-yue SUN is the research director of National Evaluation Centre for the Toxicology of Fertility Regulating Drug, a laboratory has acquired the GLP certificate of CFDA(China Food And Drug Administration). 258 study projects being carried out in his laboratory, he has published more than 312 theses in china and abroad reputed journals

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an important public health problem. CP/CPPS is a poorly understood entity characterized by pelvic or perineal pain, irritative voiding symptoms, and sexual dysfunction, and, from a clinical point of view, is truly lacking a cause that would allow a more rational-driven therapy. As a common genitourinary disease of adult male, diagnosis, treatments and prognostic monitoring of prostatitis have always been the focus of clinical attention, as a result of its setbacks, such as complex pathogenesis and clinical symptoms, lacking specificity in medication and its high rate of recurrence and so on. Currently, there isn’t a “golden standard” in diagnosis of prostatitis, while the detection of biomarkers can be helpful for the diagnosis, treatment and prognostic monitoring of prostatitis. Following significant improvements of the methods of detection in biological fluids, a number of prostate inflammation biomarkers were identified and quantified, in peripheral blood, urine and seminal plasma. In fact, white blood cells (WBC) count in expressed prostatic secretions (EPS) has long been considered as the marker of prostatitis. However, it does not appear to be the optimal marker of inflammation and the current categorization of chronic prostatitis/chronic pelvic pain syndrome III B and asymptomatic inflammatory prostatitis as inflammatory or non-inflammatory based on WBC count appears to offer little clinically useful information. And whilst WBC can be found in the prostatic fluid or seminal plasma of asymptomatic men as well as in that of men with pelvic pain. Also, the measures of the NIH-CP Symptom Index in symptomatic men show no correlation with WBC in EPS or seminal plasma. As the prostatitis biomarkers, cytokines/chemokine may have high sensitivity and good specificity. Cytokines are regulatory proteins released by various cellular subtypes that promote intercellular communication and immune responses. Chemokines are a subset of cytokines that recruit and activate immune cells to sites of inflammation. Interleukin 8 (IL-8) is a pro-inflammatory cytokine and plays an important role in different inflammatory diseases. Significant correlations between IL-8 levels and symptom score results were found. IL-8 values strongly correlated with CP/CPPS. Moreover, the patients with higher levels of IL-8 reported the worst symptoms. The study has shown that IL-8 was significantly elevated compared to controls in patients with CP/CPPS IIIA, CP/CPPS IIIB and benign prostatic hyperplasia (BPH). IL-8 is a reliable biomarker in seminal plasma for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), and for BPH, and also the IL-8 levels were correlated with symptom scores and serum PSA values, increasing its value as a biomarker for prostate inflammation. Monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) recruit monocytes and macrophages via their release from fibroblasts and macrophages in joints of patients with rheumatoid arthritis and perpetuate the inflammatory process. For MCP-1 and MIP-1α, chronic pelvic pain syndrome subtypes had statistically higher levels than the control group and patients with benign prostatic hyperplasia. MCP-1 and MIP-1α within the prostatic fluid in both chronic pelvic pain syndrome subtypes provide candidate future biomarkers for chronic pelvic pain syndrome. In addition, macrophage inflammatory protein-1α increase in expressed prostatic secretions provides a new marker for clinical pain in chronic pelvic pain syndrome patients. Given these findings prostatic dysfunction likely has a role in the pathophysiology of this syndrome

Yan-qiang Liu has completed his PhD in Nanjing Agricultural University, postdoctoral study in Chinese Military Medicine Academy, and visiting and co-operative studies in Pisa University. He is Professor of College of Life Sciences Nankai University. He has published more than 80 papers in reputed journals, and has been serving as an editorial board member of Acta Nutrimenta Sinica and the referee of many academic journals

In the present study, we established an in vitro model of hypoxic-ischemia via exposing PC12 cells and primary neurons of newborn rats to oxygen–glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuronal viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits expression. The results indicated that OGD exposure reduced the cell viability, increased apoptosis, decreased the GluR2 expression, and decreased the voltage-activated potassium currents in PC12 cells, and genistein partially reversed the effects induced by OGD. In primary neurons, OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD in primary neurons. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K+ efflux, a decrease in Na+ influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2. * This work was supported by the Natural Science Foundation of Tianjin City (15JCYBJC24500), the National Natural Science Foundation of China (No. 31272317), and the 111 Project (B08011).