Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 15th Annual European Pharma Congress Frankfurt, Germany.

Day 2 :

Keynote Forum

Anna Szemik-Hojniak

University of Wroclaw, Poland

Keynote: Dipeptides with a short side chains as potential drug candidates

Time : 10:00-10:30

Conference Series Pharma Europe 2018 International Conference Keynote Speaker Anna Szemik-Hojniak photo
Biography:

Anna Szemik-Hojniak has completed her PhD in Radiochemistry from the University of Wroclaw and Post-doctoral Studies from Solvay Foundation (Belgium), KU Leuven (Belgium) and Centre of Nuclear Researches (Strasburg, France). She is an experienced Researcher and Academic Teacher and occupied with Organic Molecular Photophysics. She has published more than 50 papers in reputed scientific journals and has been serving as a Reviewer. In 2014 and 2015, she organized a Mini Symposium on “Photophysics of Electron and Proton Transfer” in the framework of ICCMSE2014 Conference in Athens (Greece) and during Pharma 2015 and Pharma 2016 she gave the Keynote Lectures on Drug Design. Presently, she serves as General Secretary and the Board Director of INWES-ERI Corporation, Operational Partner of UNESCO (headquarters-Ottawa, Canada).

Abstract:

Quinoxaline and its derivatives are at the forefront of organic compounds with a wide range of biological activities (antibacterial, antiviral or anticancer properties). Recently, we synthesized dipeptides containing quinoxaline-derived amino acid side chains. They show a limited steric hindrance and may exist in numerous conformations. This property can be explored in pharmaceutical applications. In this talk, the results of experimental absorption and emission steady state and time-resolved spectroscopy along with theoretical (DFT) calculations on the synthesized dipeptides containing the 3-(quinoxalin-6-yl)alanine residue will be presented. These are: N-(3-(2, 3-diphenylquinoxaline-6-ylo)alanylo) glycine dipeptide [Pe-DPhQ] and diphenylquinoxaline (DPhQ) pair, as well as N-(3-(2, 3(pirydine-2-ylo) quinoxaline-6-ylo)alanylo) glycine dipeptide (Pe-DPiQ) and dipyridyl-iso-quinoxaline (DPiQ) pair. The DFT calculations reveal that Pe-DPiQ dipeptide is the most stable and may exist in three ground state optimized isomers. In this isomer, the OH...N hydrogen bond is present and the excited state proton transfer can occur. At room temperature, in highly polar solvents, emission (403 nm) decays bi-exponentially (τ1= 2.0 ns, τ2= 8.9 ns) while with lowering temperature, besides a weak fluorescence that is slightly redshifted (410 nm; 2.5 and 38.2 ns); also, the phosphorescence band at 495 nm (τ1=1.0 μs and τ2=9.0 μs) is observed. On the other hand, at elevated temperatures, a new broad, structurless and strongly red shifted fluorescence band (563 nm) appears (the Stokes shift ~12000 cm-1) suggesting the strong excited state charge transfer (CT) interactions. It’s origins from the isomer where one of the two pyridine side rings are more or less coplanar with respect to the quinoxaline plane. One may conclude that recognizing of the electronic structure, the CT and proton transfer abilities in the short peptides are highly important for explaining the splitting and conformational dynamics in proteins. This in turn allows treating such systems as novel groups of potential drug candidates.

Conference Series Pharma Europe 2018 International Conference Keynote Speaker Sergey Suchkov photo
Biography:

Sergey Suchkov received his MD from Astrakhan State Medical University. In 1985, he received his PhD from the I M Sechenov Moscow Medical Academy and in 2001, his Doctorship Degree at the Nat Institute of Immunology, Russia. From 1987 through 1989, he was a Senior Researcher, Koltzov Institute of Developmental Biology. From 1989 through 1995, he was a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004, he was the Chair of the Department of Clinical Immunology, Moscow Clinical Research Institute. He was a Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, he is a Chair at the Department for Personalized and Translational Medicine, I M Sechenov First Moscow State Medical University. He is a Member of the New York Academy of Sciences, USA; American Chemical Society (ACS), USA; American Heart Association (AHA), USA; EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ARVO (American Association for Research in Vision and Ophthalmology); ISER (International Society for Eye Research) and PMC (Personalized Medicine Coalition), Washington, USA.

Abstract:

A new systems approach to diseased states and wellness results in a new branch in the healthcare services, namely, personalized medicine (PM). To achieve the implementation of PM concept into the daily practice including clinical cardiology, it is necessary to create a fundamentally new strategy based upon the subclinical recognition of bio-indicators (biopredictors and biomarkers) of hidden abnormalities long before the disease clinically manifests itself. Each decision-maker values the impact of their decision to use PM on their own budget and well-being, which may not necessarily be optimal for the society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment to thus provide more tailored measures for the patients and persons-at-risk resulting in improved outcomes whilst securing the healthy state and wellness, reduced adverse events, and more cost effective use of health care resources. One of the most advanced areas in cardiology is atherosclerosis, cardiovascular and coronary disorders as well as in myocarditis. A lack of medical guidelines has been identified by the majority of responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PM into the daily practice of cardiologists. Implementation of PM requires a lot before the current model, “physician-patient” could be gradually displaced by a new model, “medical advisor-healthy person-at-risk”. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PM to elicit the content of the new branch.

Break: Networking and Refreshments Break 11:00-11:15 @ Foyer
  • Novel Drug Delivery Systems | Pharmacological Sciences | Drugs and Regulations | Pharmacognosy and Phytochemistry | Types of Pharmaceutical Formulations | Radiochemistry | Pharmacology and Toxicology of Drugs | Biomarkers and Personalized Medicine
Location: Odenwald
Speaker

Chair

Bimal Roy Krishna

Touro University, USA

Speaker

Co-Chair

Sergey Suchkov

I.M. Sechenov First Moscow State Medical University, Russia

Speaker
Biography:

Bimal Krishna is currently Professor and Director of Pharmacology at the College of Osteopathic Medicine, Touro University in Nevada. He obtained a Bachelor of Science (First Class Honors) in Pharmacology and Physiology and a Doctor of Philosophy, Medicine (OB/GYN/Pharmacology) from Monash University in Australia. He also teaches for the Step 1 USMLE and COMLEX reviews for Kaplan Medical throughout the United States and in UAE, Europe, Saudi Arabia, India, Mexico and the Caribbean. He has been teaching online for Kaplan University for over seven years. He has contributed to numerous publications and is a Member of a number of organizations including Fellow of American College of Clinical Pharmacology. His research background is in Maternal and Neonatal Pharmacology, specifically looking at materno-fetal transfer utilizing the perfused human placental and cultured syncytiotrophoblast model. Complementary and Alternative Medicine is another area of interest.

Abstract:

During pregnancy and the post-partum period, significant physiological changes occur to meet the demands of the fetus. These changes typically peak in the second trimester. Maternal plasma volume, cardiac output and glomerular filtration increase up to 50%. Increasing body fat increases the volume of distribution of highly lipid soluble drugs. Nausea, vomiting and delayed gastric emptying may impact drug absorption. The placenta plays a significant role in nourishing and maintaining fetal integrity along with the amniotic fluid. The placenta is fundamentally the exchange organ for nutrients and gaseous substances and drugs. Essentially drugs with low molecular weight and high lipid solubility will traverse the placenta. Hence, placental insult will have significant impact on the fetus. Pre-conception planning is essential, particularly in high risk patients. During pregnancy, nausea, vomiting, constipation and gastroesophageal reflux disease (GERD) are likely to occur and can be treated with therapeutic and non-therapeutic approaches. Thereafter, pregnancy-influenced issues, acute-care issues and chronic illnesses require immediate therapeutic intervention. Pre-eclampsia, seizures, HIV, STDs can certainly pose serious adverse consequences for the fetus. Drugs of abuse are a concern as they rapidly traverse the placenta and are responsible for IUGR, fetal death in utero, carcinogenic effects and placental abruption. This presentation addresses the current therapeutic trends in pregnancy and contraindicated drugs. It also covers optimizing medication use in pregnancy and effects of drug abuse.

Speaker
Biography:

Leszek Paczek, Head of the Department of Immunology, Transplant Medicine and Internal Diseases at the Warsaw Medical University, is an expert in Transplant Medicine and Nephrology. He has authored over 400 journal articles and given lectures and presentations on numerous international and national congresses. Among numerous scientific interests, he is devoted to research on the determinants of side effects and toxicity of immunosuppressive drugs with an emphasis on the role of metabolites of immunosuppressive agents. His ongoing and future projects are aimed at the development of procedures allowing the individualization of immunosuppression after solid organ transplantation.

Abstract:

Statement of the Problem: The immunosuppressive drugs and their metabolites may often be toxic. Advances in laboratory methods enable measurement of real levels of both; a specific immunosuppressive drug and their metabolites. Older, but still widely used immunoassays yield fluctuating results and what is more, results that are often about 25-30% higher than the actual levels. On the other side, novel liquid chromatography combined with mass spectrometry (LC/MS) method obtains accurate drug level measurements.

Methodology & Theoretical Orientation: LC/MS and immunoassays (IA) were applied to assess levels of both parent drugs and its metabolites in the cohort of 834 patients after kidney transplantation (KTX), mean age: 49.13 years, median: 64.95 months after KTX. 256 (30.7%) patients were treated with cyclosporine A (CsA) and 449 (53.8%) patients were given tacrolimus (Tac).

Findings: Results of analyses of immunosuppressive drugs and their metabolites as well as differences between IA and LC/MS are presented in Table 1. Tac LC/MS to IA mean difference was 1.78 ng/ml; 89.9% of IA results overestimated real Tac levels. CsA LC/MS to IA mean was 28.8 ng/ml; 94.3% of IA results overestimated real CsA levels.

Conclusion & Significance: This preliminary study warrants the initiation of multi-centre studies of serum drug levels and metabolite pharmacokinetics. Future studies should include the analysis of large data sets, as well as long-term follow-up of patients and grafts.

Speaker
Biography:

 

Taishi Higashi took part in a half-year internship of Evonik Röhm GmbH & Co., Darmstadt, Germany in 2008. Then, he obtained PhD (Pharmaceutical Sciences) at Kumamoto University, Japan in 2009. In 2009-2011, he became a Research Scientist of Taisho Pharmaceutical Co., Ltd, Japan, and engaged self-medication business such as oral solid formulation. From 2011, he works as a Research Associate in the Department of Physical Pharmaceutics, Graduate School of Pharmaceutical Sciences at Kumamoto University, Japan. In 2013-2014, he became a Guest Researcher at Faculty of Engineering, National University of Singapore. From 2016, he holds the additional post as a Technical Adviser in CyDing Co., Ltd. His research topic is “supramolecular pharmaceutical sciences” which combines Pharmaceutical Sciences and Supramolecular Chemistry.

Abstract:

Polyethylene glycol (PEG) modification (PEGylation) is one of the best approaches to improve the stabilities and blood half-lives of protein drugs; however, PEGylation dramatically reduces the bioactivities of protein drugs. Here, we present “self-assembly PEGylation retaining activity” (SPRA) technology via a host–guest interaction between PEGylated b-cyclodextrin (PEG-b-CyD) and adamantane-appended (Ad)-proteins. Firstly, we prepared SPRA-insulin and SPRA-lysozyme. Both SPRA-proteins showed high stability against heat and trypsin digest, comparable with that of covalently PEGylated protein equivalents. Importantly, the SPRA-lysozyme possessed ca. 100% lytic activity, whereas the activity of the covalently PEGylated lysozyme was ca. 23%. Additionally, SPRA-insulin provided a prolonged and peak-less blood glucose profile when compared with insulin glargine. It also showed no loss of activity. In contrast, the covalently PEGylated insulin showed a negligible hypoglycemic effect. Next, we prepared SPRA-bromelain, because bromelain is known to degrade the extracellular matrix (ECM) in pancreatic cancer and increase the penetration of antitumor agents, although the blood half-life of bromelain is short. SPRA-bromelain showed high in vitro ECM-degrading activity, and enhanced not only the accumulation of FITC-dextran (2 MDa) in the tumor, but also the in vivo antitumor activities of doxorubicin and DOXIL. These findings indicate that SPRA technology has the potential as a generic method, surpassing conventional PEGylation methods for proteins.

Speaker
Biography:

Eriona Petro received her Master’s Degree in Pharmacy (MPharm) from the University of Tirana, Albania. She worked for two years as a Community Pharmacist following her position as Sales and Application Manager for the representative office of Siemens Healthcare in Albania. She has been working as the Vice Technical Director of the Regional Directory of Health in the District of Durres since 2016 and has been a part-time Lecturer at “Aleksander Moisiu” University, Durres, Albania since 2012.

Abstract:

Statement of the Problem: Pharmaceutical expenditures make up an increasing percentage of healthcare costs. One strategy in cost minimizing without compromising quality of medications is switching brand-name drugs to generics. Eventhough generics are comparable in terms of efficacy, safety and quality with their original drugs and can be used interchangeably, there are still concerns regarding their usage. Understanding physicians’ knowledge and attitude about generics may help ensure more cost-effective treatments. The market share of generic drugs in Albania is considerable. This study aimed to investigate the perceptions of physicians towards generic drug prescribing.

Methodology & Theoretical Orientation: Physicians from 18 primary healthcare centers in the district of Durres, Albania participated in the study conducted in January 2018. A paper-based questionnaire was used to assess their knowledge and attitude towards use of generic drugs. The study was approved by the Regional Directory of Health, Durres. Descriptive statistical analysis was used to examine the results.

Findings: 60% of 109 physicians that participated in the study declared to have very good knowledge of the term ‘‘generic drug’’. The majority of them (70%) prescribed generics daily. However, no correlation between years of experience and frequency of prescribing generics was reported (p>0.05). Approximately, 42% of the physicians responded that the price difference between brand and generic drugs was one of the influential factors when deciding the right medication for treatment. Only 11% of the physicians reported generics as being less safe and effective compared to the original drugs.

Conclusion & Significance: Although it appeared that physicians are well informed about generic drugs, they still have concerns about their quality and safety. The results of this study highlight the need in suggesting the implementation of a national educational program about generics for physicians in order to overcome barriers towards generic prescribing.

Speaker
Biography:

Ladislav Novotny got his PharmD from Charles University and his PhD from Czechoslovak Academy of Sciences in Prague, Czech Republic. He obtained his Specialization in the field of Pharmacology and Toxicology of Drugs. He received a Doctor of Sciences at Slovak Academy of Sciences. He worked at the Czech Academy of Sciences in Prague, at Comenius University in Bratislava and at the Cancer Research Institute of the Slovak Academy of Sciences in Bratislava. He spent a substantial amount of time at M D Anderson Cancer Center in Houston, USA. He served as a Dean at the Faculty of Pharmacy, Kuwait University from 2003 to 2014. He has authored more than 120 original scientific papers, 36 reviews and 7 patents. His scientific work is in the area of anticancer agents, experimental cancer therapy and in the area of studying physico-chemical and biological properties of various natural and synthetic compounds.

Abstract:

Cadmium (Cd) is a toxic heavy metal and industrial pollutant of the environment. Its biological half-life in humans is approximately 30 years. The flavonoid, quercetin (QE) is distributed in plants and is a part of human diet. Many studies demonstrated potential therapeutic effects of QE. Additionally, some studies demonstrated protective effects of QE against Cd-induced toxicity in healthy intact animals. The aim of our study was to investigate the effect of QE and Cd on proliferation in already cancerous cells. Human cancer cells of astrocytoma 1321N1 served as our experimental model. The simultaneous exposure of the cells to QE and Cd (16 μM), significantly reduced cell viability to 21% and 7% at 100 and 200 µM QE, respectively, compared to viability decrease by Cd alone to 81% (48-hours exposure). Other experiments with QE pre-treatment and Cd exposure or co-exposure with QE were performed. The observed effects were time and concentration-dependent. In general, these experiments show the ability of QE to induce cytotoxicity in an in vitro model of cancer cells that may undergo further carcinogenic transformation due to exposure to Cd. Cd alone was less cytotoxic in 1321N1 cells and cells did not benefit from QE presence in the medium. In general, a synergetic anti-proliferative interaction of Cd and QE in malignantly transformed cells was shown. This may represent a novel aspect of QE protective effects on organisms that are exposed to toxic agents as it would not only protect normal cells from toxicity of these toxic agents but would contribute to removal of already malignantly transformed cells from the system or removal of any cell undergoing malignant transformation.

Break: Lunch Break @ 13:20-14:20 Restaurant Palate Friend

Aihua Liang

China Academy of Chinese Medical Sciences, China

Title: Chinese traditional medicine - The fruitful approach to new drug discovery
Speaker
Biography:

Abstract:

Traditional Chinese medicine is an ancient remedy with a long history of thousands of years in China. The application experiences of Chinese medicines (CMs) have been recorded in a large number of ancient and current literatures, but the mechanism of its treatment is not clear. Impacted by modern medical research in recent decades, the chemical composition and therapeutic mechanism of CMs have been studied, so as to develop many new drugs with better curative effects. In China, CMs are the important ways to develop new drugs. The development of artemisinin and arsenic preparations are the typical examples. In the 70s of last century, Prof. Tu Youyou led a research team that aimed to discover antimalarial drugs. When they retrieved the Chinese ancient medical literatures, they found that southernwood appeared in the prescriptions for malaria treatment with highest frequency. After determination of the plant origin of southernwood by textual research, they tested the extract of Artemisia annua Linn for anti-malaria effect on animal malaria models. The initial experiments were not optimistic in antimalarial activity. By reviewing an ancient medical book "zhou Hou Bei Ji Fang”which was written by Ge Hong, a Chinese ancient doctor in one thousand and eight hundred years ago, Prof. Tu was enlightened by the preparation method  recorded in this book in which southernwood was prepared as fresh juice and oral administered to treat malaria. She changed the preparation methods from hot extraction to merceration, and successfully found Artemisinin, a powerful anti-malaria lead compound. Artemisinin was approved to market in China in 1986. Since then, various derivatives of artemisinin have been marketed and benefited hundreds of millions of people. Another example is the development of arsenic preparations in the treatment of acute myeloid leukemia. Arsenics have been used in Chinese traditional medicine for more than 2000 years. Although arsenics have been abandoned in clinic worldwide because of consideration of their toxicity in the last few decades, they are always in use in China until now. In 1970s, Chinese doctors noticed that a formula containing three toxic Chinese materia medica, arsenic, calomel and venenum bufonis,was very popular in cancer patient which was used in a folk clinic. The doctors processed this formula to be a compound injection and used it for the treatment of leukaemia. Surprisingly, it had a good effect. Subsequently, they screened the efficacy of each ingredient in the formula and found that arsenic trioxide had the best effect on leukemia with a good tolerance in patients. Science then, various clinical studies have shown that arsenic trioxide had a prominent targeted efficacy for acute promyelocytic leukemia (APL). Now, FDA already approved the first line treatment of arsenic trioxide combined with retinoic acid for treatment of APL with t (15, 17) translocation or PML/RAR alpha gene expression. Today, prognoses in the treatment of APL have drastically improved. A standard treatment of ATRA in combination with arsenic trioxide can result in a clinical remission in approximately 90% of patients. In addition, a formula, Compound Huang Dai tablets containing realgar has also been used to treat leukemia for more than 40 years in China. It also shows good curative effect. From the examples mentioned above we can conclude that traditional Chinese medicine is a valuable source for new drug discovery, because there are plenty of clinical and pharmaceutical experiences to support the efficacy and safety. It should be a cost saving and effective way to develop new drugs.

Speaker
Biography:

Jafari S received her Master’s Degree in Analytical Chemistry from the University of Tabriz and is currently pursuing her Doctorate of Chemistry in the Analytical Area at Imam Khomeini International University. In addition to her Master’s Degree, she has well travelled during her schooling and as such has acquired a wide range of different chemistry techniques. With this experience, she gleaned and culminated a wide scope of techniques to develop a novel method for targeting various cancers efficiently with relatively low costs as compared to customized patient medicines. With a generic customized cancer drug delivery system as described in her work, a new field of focus is presented that can make large strides in the fight against breast cancer.

Abstract:

Polyurethanes have great variety of physical and chemical properties due to different building blocks in their structure which makes it possible to be used for different biomedical and pharmaceutical applications. The most important application of these polymers is as a biocompatible, smart and controllable drug carrier, which directs the anticancer drugs sufficiently to the cancerous cells for solving the problem of inadequate drug cargo with fewer side effects to the cancerous tissue cells. In this article, a new drug delivery system is introduced which is a smart, controllable (pH-sensitive), multifunctional, magnetic polyurethane (SCMMP) nano composite composed of isocyanate as a main chain and cyclodextrin as a chain extender with magnetic nano particles in their structure. Then consequently, the bulk structure, size and morphology and magnetic characteristic of the synthetic nano-composite was characterized through different accepted analytical techniques such as FT-IR, TGA, XRD, TEM, SEM, DLS and VSM, respectively. The SCMMP was used for loading tow effects, currently used pharmaceutical cancer agents of metatroxate and doxorubicin with high loading efficiency of 87% and 89%, respectively. Dual drug loaded nano composite release behaviour was investigated in three different pHs of 4.5, 5.4 and 7.4. According to the concentration profile, low release percentage in the pH of 7.4 for long term circulation and good stability in blood stream and high release in pH of 4.5 and 5.4 for improving vast variety of cancerous cells in physiological media were observed. Thereupon, new drug carrier systems have great efficacy for cancer therapy. The MTT calorimetric method was used to track the presented nano composite eligibility as a polymer based drug delivery system. Different cellular tests of MTT assay, DAPI staining, cellular uptake and cell cycle was done on Nan composite/DOX/MX combination vs. free DOX/MX to validate it as a nano carrier. Biocompatibility of the nano carrier was done using hemolysis assay through checking on human red blood cells (HRBCs) with very fine results. According to the results, the introduced system is very effectible in delivering synchronous therapeutic agents of DOX and MX to the cancerous cells and on other hand for in vivo usage in the future.

  • Video Presentation

Session Introduction

Parnia Mobasheran

Tehran University of Medical Sciences, Iran

Title: Possible oxidative stress and inflammatory response evoked by 5-HT1B/1D agonist in rat kidney
Speaker
Biography:

Parnia Mobasheran graduated from IAUPS with PharmD in Pharmaceutical Science in 2017. She ranked 7th in the Nationwide Basic Science Exam. At present she is studying German language and completing her Internship at Alborz Health Center. She defended her PharmD thesis based on the effect of sumatriptan administration on renal ischemia reperfusion injury in rat. She has participated in several scientific conferences in the field of Pharmacy and has also attended two summer schools on the topics, Pharmacology and Clinical Pharmacy. She is very interested in pursuing her educational goals and conducting more research in the field of Pharmacology.

Abstract:

Aim: Ischemic/reperfusion injury is the common cause for acute kidney injury. The aim of the present study is to investigate the effect of 5HT1B/1D agonist on the renal ischemic injury in rats.

Method: Ischemia/reperfusion injury was induced by a 45-minute occlusion of the bilateral renal pedicles and a 24-hour reperfusion. Our experimental groups consist of sham, control, and treatments that received three doses of sumatriptan (5, 10, 20 mg/kg). Nitric oxide kit, selective and non-selective inhibitor of nitric oxide synthase (NOS), aminoguanidine, and L-NAME were used to determine the role of Nitric oxide system. Superoxide dismutase (SOD) and malondialdehyde (MDA) of the tissue were measured to investigate the role of inflammation. Histopathological study of the kidney was performed too.

Result: Serum creatinine (Cr) and blood urea nitrogen (BUN) were measured after 24 hours of reperfusion. Sumatriptan in doses of 10, 20 mg/kg increased Cr and BUN significantly. There was a significant increase (P<0.05) of nitric oxide (NO) level in the treatment group compared with the level of the control group. Comparing to sumatriptan alone, the result of aminoguanidine administration showed a significant decrease (P<0.01) in BUN and (P<0.05) Cr. Besides, there was a significant increase (P<0.05) in BUN level, but not in Cr level when both L-NAME and sumatriptan administered within one hour. We also observed a reduction of SOD level (P<0.05) and increased serum level of MDA (P<0.001); furthermore, the histopathological result indicates kidney damage.

Conclusion: The study conducted showed an increase in kidney damage due to use of sumatriptan. We proved that NO plays a significant role in this injury. Also, decreased levels of creatinine and blood urea nitrogen in response to the aminoguanidine injection showed that inducible NO was involved in this injury.