Indian Journal of Experimental Biology

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VOLUME 48

NUMBER 7

JULY 2010

CODEN: IJEB (A6) 48 (7) 617-768 (2010)

ISSN: 0019-5189 (Print); 0975-1009 (Online)

 

CONTENTS

 

Special issue on
Environmental Pollution and Experimental Pharmacological Approaches

 

Foreword

619

Theodore Rozema

 

 

 

Preface

621

S J S Flora & R Vijayaraghavan

 

 

 

Review Articles

 

Idiopathic environmental intolerances (IEI): From molecular epidemiology to
molecular medicine

625

      C De Luca, G Scordo, E Cesareo, D Raskovic, G Genovesi & L Korkina

 

 

 

Developmental exposure to lead and late life abnormalities of nervous system

636

      Riyaz Basha & G Rajarami Reddy

 

 

 

Pharmacological agents in the prophylaxis/treatment of organophosphorous
pesticide intoxication

642

    Kazim Husain, Rais A Ansari & Leon Ferder

 

 

 

Association of functionally important polymorphisms in cytochrome P450s with
squamous cell carcinoma of head and neck

651

      Munindra Ruwali & Devendra Parmar

 

 

 

Arsenic and fluoride: Two major ground water pollutants

666

      Swapnila Chouhan & S J S  Flora

 

 

 

Resistance to heavy metal toxicity in organisms under chronic exposure

679

      Anatoliy Bozhkov, Vladimir Padalko, Viktoria Dlubovskaya & Natalia Menzianova

 

 

 

Cellular and molecular mechanisms of dichlorvos neurotoxicity: Cholinergic, nonchlolinergic, cell signaling, gene expression and therapeutic aspects

697

    B K Binukumar & K D Gill

 

 

 

Effects of diesel exhaust, heavy metals and pesticides on various organ systems :
Possible mechanisms and strategies for prevention and treatment

710

     Kavita Gulati, Basudeb Banerjee, Shyam Bala Lall & Arunabha Ray

 

 

 

(Contd)

Papers

 

Altered glucose homeostasis in response to aluminium phosphide induced cellular
oxygen deficit in rat

722

     Raina Dua, Vijay Kumar, Aditya Sunkaria & K D Gill

 

 

 

Cyanide-induced changes in the levels of neurotransmitters in discrete brain regions
of rats and their response to oral treatment with a-ketoglutarate

731

    Janardhanan Hariharakrishnan, Ravindra M Satpute & Rahul Bhattacharya

 

 

 

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity

737

      Srinivas Pentyala, Jeanine Ruggeri, Amulya Veerraju, Zhangzhang Yu,
Anjori Bhatia, Durisala Desaiah & Parminder Vig

 

 

 

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination
with insect growth regulator, diflubenzuron, for establishing no observed adverse
effect level (NOAEL)

744

      Yangchen Doma Bhutia, Anshoo Gautam, Neeti Jain, Fakhruddin Ahmed,
Manoj Sharma, Ram Singh, Satish Kumar, Muralidhar Jayavantarao Mendki,
Pravin Kumar & R Vijayaraghavan

 

 

 

Prophylactic efficacy of combination of DRDE-07 and its analogues with
amifostine against sulphur mustard induced systemic toxicity

752

      Anshoo Gautam, Alka Gupta, Vinay Lomash, S C Pant & R Vijayaraghavan

 

 

 

Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental diabetic rats

762

      Hitesh Vashrambhai Patel & Kiran Kalia

 

 

 

Announcement

624

 

 

覧覧覧覧覧覧覧

 

 

Announcement

 

International 2nd Biennial Conference

 

New Developments in Drug Discovery from Natural Products and
Traditional Medicines

(20th 24th November, 2010)

 

      The conference will be held at National Institute of Pharmaceutical Education and Research (NIPER), Phase X, Sector-67, S.A.S. Nagar 160062, India. The conference will focus on frontiers of natural product and traditional medicines based drug discovery programs; participation of the pharmaceutical industries in natural drug development programme; and possible collaboration of scientists/researchers globally for drug discovery from natural products. The registration for participation is open from March 1, 2010. For further details, please contact Prof K. K. Bhutani, Organizing Secretary/Convener, Department of Natural Products,
National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, SAS Nagar 160062, India. E-mail: ddnptm@niper.ac.in; kkbhutani@niper.ac.in. Telefax: 0172-2232208; 0172-2292036 (Websites: www.niper-ddnptm.com; www.naturalproducts-niper.com; www.niper.gov.in).

 

 
Author Index

 


Ahmed Fakhruddin 744

Ansari Rais A 642

 

Banerjee Basudeb 710

Basha Riyaz 636

Bhatia Anjori 737

Bhattacharya Rahul 731

Bhutia Yangchen Doma 744

Binukumar B K 697

Bozhkov Anatoliy 679

 

Cesareo E 625

Chouhan Swapnila 666

 

De Luca C 625

Desaiah Durisala 737

Dlubovskaya Viktoria 679

Dua Raina 722

 

Ferder Leon 642

Flora S J S 666

 

Gautam Anshoo 744, 752

 

 

Genovesi G 625

Gill K D 697, 722

Gulati Kavita 710

Gupta Alka 752

 

Hariharakrishnan Janardhanan 731

Husain Kazim 642

 

Jain Neeti 744

 

Kalia Kiran 762

Korkina L 625

Kumar Pravin 744

Kumar Satish 744

Kumar Vijay 722

 

Lall Shyam Bala 710

Lomash Vinay 752

 

Mendki Muralidhar 744

 Jayvantarao

Menzianova Natalia 679

 

 

Padalko Vladimir 679

Pant S C 752

Parmar Devendra 651

Patel Hitesh Vashrambhai 762

Pentyala Srinivas 737

 

Raskovic D 625

Ray Arunabha 710

Reddy G Rajarami 636

Ruggeri Jeanine 737

Ruwali Munindra 651

 

Satpute Ravindra M 731

Scordo G 625

Sharma Manoj 744

Singh Ram 744

Sunkaria Aditya 722

 

Veerraju Amulya 737

Vig Parminder 737

Vijayaraghavan R 744,752

 

Yu Zhangzhang 737

 


 

覧覧覧覧

 

Keyword Index

 


Acute toxicity 744

Alcohol 651

Aluminium phosphide 722

Antidote 642

Amifostine 752

Antioxidants 625, 666, 710

Arsenic 666, 762

Attracticide 744

Azadirachta indica 710

 

Behavioral 697

 

Ca2+ flux 737

Carcinoma 651

Chelators 625, 666

Combination treatment 752

Cyanide 731

Cynide antidote 731

Cytochrome P450 651

Cytoprotection 752

Cytotoxicity 752

 

Developmental exposure 636

Diabetes mellitus 762

Dichlorvos 697

Diesel exhaust 710

Diflubenzuron 744

Environmental exposure 636

Environmental risk factors 651

Environmental toxicants 710

Epigenetics 636

 

Fluoride toxicity 666

Fructose-1,6-bisphosphate 722

 

Genetic polymorphism 625

Glucose homeostasis 722

Glucose-6-phosphate 722

Glutathione s-transferases 651

 

Heavy metal ions 679

Heavy metal toxicity 710, 737

Heneicosane 744

Hormesis 679

 

Idiopathic environmental
 intolerances 625

Inositol 1,4,5-trisphosphate 737

Insect Growth Regulator 744

 

a-Ketoglutarate 731

 

Lead 636

Microsomes 737

 

Neurodegeneration 636

Neurotoxicity 697

Neurotransmitters 731

Nicotinic receptors 697

NOAEL 744

 

OPIDN 642

Organism resistance 679

Organophosphate 697

Organophosphorus pesticide 642

Oxidative stress 710, 762

 

Percutaneous 752

Pesticides 710

Polymorphism 651

Prophylatic agents 642

 

Redox imbalance 625

Renal tissue 762

 

Sub-acute toxicity 744

Sulphur mustard 752

 

Tobacco 651

  

 

 

 

 

Review Articles

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 625-635

 

Idiopathic environmental intolerances (IEI): From molecular epidemiology to molecular medicine

C De Luca1, G Scordo2, E Cesareo1, D Raskovic1, G Genovesi3 & L Korkina1*

Laboratory of Tissue Engineering & Cutaneous Pathophysiology1, Istituto Dermopatico dell棚mmacolata, Rome, Italy

Department of Medical Sciences - Clinical Pharmacology2, University Hospital, Uppsala. Sweden;

Department of Medical Pathophysiology3, Policlinico Umberto I, University of Rome 鏑a Sapienza, Rome, Italy

 

Inherited or acquired impairment of xenobiotics metabolism is a postulated mechanism underlying environment-associated pathologies such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, dental amalgam disease, and others, also collectively named idiopathic environmental intolerances (IEI). In view of the poor current knowledge of their etiology and pathogenesis, and the absence of recognised genetic and metabolic markers of the diseases. They are often considered 杜edically unexplained syndromes,. These disabling conditions share the features of poly-symptomatic multi-organ syndromes, considered by part of the medical community to be aberrant responses triggered by exposure to low-dose organic and inorganic chemicals and metals, in concentrations far below average reference levels admitted for environmental toxicants. A genetic predisposition to altered biotransformation of environmental chemicals, drugs, and metals, and of endogenous low-molecular weight metabolites, caused by polymorphisms of genes coding for xenobiotic metabolizing enzymes, their receptors and transcription factors appears to be involved in the susceptibility to these environment-associated pathologies, along with epigenetic factors. Free radical/antioxidant homeostasis may also be heavily implicated, indirectly by affecting the regulation of xenobiotic metabolizing enzymes, and directly by causing increased levels of oxidative products, implicated in the chronic damage of cells and tissues, which is in part correlated with clinical symptoms. More systematic studies of molecular epidemiology, toxico- and pharmaco-genomics, elucidating the mechanisms of regulation, expression, induction, and activity of antioxidant/detoxifying enzymes, and the possible role of inflammatory mediators, promise a better understanding of this pathologically increased sensitivity to low-level chemical stimuli, and a solid basis for effective individualized antioxidant- and/or chelator-based treatments.

Keywords: Antioxidants, Chelators, Genetic polymorphism, Idiopathic environmental intolerances, Redox imbalance

 

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 636-641

 

Developmental exposure to lead and late life abnormalities of nervous system

Riyaz Basha1 & G Rajarami Reddy2*

1M D Anderson Cancer Center Orlando Cancer Research Institute, Orlando FL, USA

2Department of Zoology, Sri Venkateswara University, Tirupati 517 502, India

 

Role of developmental exposure to environmental agents in altering the disease process is well known. Exposure to chemical agents at critical periods of development may cause some permanent changes in the functioning of various vital systems including the nervous system in the organisms. It is not surprising to see an extensive response due to exposure to chemical agents early in life as the organ systems are more vulnerable to chemical insults during developmental stages. In some cases the response to low level environmental insults may not be obvious until adult or old age. Results from several studies have shown such latency in response to the nervous system leading to neurodegeneration in old age. Studies conducted in murine and primate models provided ample evidence for the association of developmental exposure to low levels of heavy metal lead (Pb) and Alzheimer痴 disease-like pathology during senescence. It is not clear about the reasons behind such response; however, the contribution of epigenetic mechanisms could explain the role of early events in life in inducing the late life abnormalities of nervous system. It is possible that environmental agents epigenetically modulate the gene regulation to persist the response silent for a long period of time and to result pathological outcomes significantly later in life. This article will summarize the association of early life exposure to environmental agents and late-life abnormalities with an emphasis on developmental exposure to Pb and neurodegeneration in old age.

Keywords: Developmental exposure, Environmental exposure, Epigenetics, Lead, Neurodegeneration

 

Indian Journal of Experimental Biology

Vol 48, July 2010, pp. 642-650

 

Pharmacological agents in the prophylaxis/treatment of organophosphorous pesticide intoxication

Kazim Husain1*, Rais A Ansari2 & Leon Ferder1

1Department of Physiology, Pharmacology and Toxicology, Ponce School of Medicine, Ponce, PR 00732, USA

2Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL, USA

 

Organophosphorus pesticide poisoning causes tens of thousands of deaths each year across the world. Poisoning includes acute cholinergic crisis as a result of AChE inhibition, intermediate syndrome (IMS) due to neuromuscular necrosis and organophosphate-induced delayed neuropathy (OPIDN) due to inhibition of neuropathy target esterase (NTE). Standard treatment for acute poisoning involves administration of intravenous atropine, oxime 2-PAM to counter AChE inhibition and diazepam for CNS protection. However clinical trials showed ineffectiveness of the standard therapy regimen. Although new oximes that can reactivate both peripheral and cerebral AChE and other prophylactic agents such as human serum butyrylcholinesterase (Hu BChE), sodium bicarbonate, huperzine A (a reversible ChE inhibitor) with imidazenil (a GABAA receptor modulator) have been proved effective in animal models, systematic clinical trials in patients are warranted. For IMS which is non-responsive to standard therapy, supportive therapy specifically artificial respiration followed by recovery is indicated. For OPIDN which has a different target (NTE) than AChE, standard therapy is ineffective. However neuroprotective drugs such as corticosteroids proved partially effective. Pretreatment with protease inhibitor PMSF has been shown to protect the aging of NTE and prevent the development of delayed symptoms in hens. Since the biology of NTE is being explored, new pharmacological agents should be developed in future. OP pesticide poisoning is a serious condition that needs rapid diagnosis and treatment. Since respiratory failure is the major reason for mortality, artificial respiration, careful monitoring, appropriate treatment and early recognition of OP pesticide poisoning may decrease the mortality rate among these patients.

Keywords: Antidote, OPIDN, Organophosphorus pesticide, Prophylatic agents

 

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 651-665

 

Association of functionally important polymorphisms in cytochrome P450s with squamous cell carcinoma of head and neck

Munindra Ruwali & Devendra Parmar*

Developmental Toxicology Division, Indian Institute of Toxicology Research (CSIR),
P O Box 80, M G Marg, Lucknow 226 001, India

Head and neck squamous cell carcinoma (HNSCC), a common malignancy that possibly involves a combination of exposure to the carcinogens and inherited genetic differences in the enzymes catalyzing their metabolism. Alcohol and tobacco consumption are the primary environmental risk factors, while polymorphism in various biotransformation enzymes such as cytochrome P450s (CYPs) and glutathione S-transferases, (GSTs) has been implicated as the major genetic risk factors for the development of HNSCC. The functionally important polymorphisms in these CYPs (1A1*2A, 1A1*2C, 1B1*2, 2E1*5B, 2E1*6, 2C19*2, 2D6*4, 2D6*10) and GSTs (GSTM1-null or GSTT1-null) were found to be significantly associated with HNSCC risk. Significant differences in the distribution of certain haplotypes of CYPs have also been reported and prevalence of certain genotype combinations of CYPs and GSTS in cases has indicated the importance of gene-gene interactions in HNSCC risk. Alcohol or tobacco use (smoking and chewing) were also found to interact synergistically with variant genotypes of these CYPs and GSTS in significantly enhancing HNSCC risk. This increase in risk associated with the variant genotypes with tobacco or alcohol use have further demonstrated the importance of gene貌nvironment interactions in determining the susceptibility to HNSCC.

Keywords: Alcohol, Carcinoma, Cytochrome P450, Environmental risk factors, Glutathione-S-transferases, Polymorphism, Tobacco

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 666-678

 

Arsenic and fluoride: Two major ground water pollutants

Swapnila Chouhan & S J S Flora*

Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior 474 002, India

Increasing human activities have modified the global cycle of heavy metals, non metals and metalloids. Both arsenic and fluoride are ubiquitous in the environment. Thousands of people are suffering from the toxic effects of arsenicals and fluorides in many countries all over the world. These two elements are recognized worldwide as the most serious inorganic contaminants in drinking water. Many studies have reported as regards to simple fluorosis and arsenicosis, but the knowledge of the joint action of these two elements is lacking and the results derived from previous studies were inconclusive. Contradictory results were reported in experimental studies in which different joint actions such as independent, synergistic and antagonistic effects were observed. This indicates that interaction mechanism of these two elements is considerable complicated and requires extensive studies. When two different types of toxicants are simultaneously going inside a human body they may function independently or can act as synergistic or antagonistic to one another. Thus there is an urge to resolve the question that how arsenic and fluoride act in condition of concomitant exposure. Although there have been reports in literature of individual toxicity of arsenic and fluoride however, there is very little known about the effects following the combined exposure to these toxicants. This review focused on recent developments in the research on the condition of individual exposure to arsenic and fluoride along with the recent updates of their combined exposure to better understand the joint action of these two toxicants.

Keywords: Antioxidants, Arsenic, Chelators, Fluoride toxicity

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 679-696

 

Resistance to heavy metal toxicity in organisms under chronic exposure

Anatoliy Bozhkov, Vladimir Padalko*, Viktoria Dlubovskaya & Natalia Menzianova

Research Institute of Biology, V N Karazin Kharkov National University, Kharkov 61077, Ukraine

 

The rate of changes of heavy metal ions concentrations in the organism or biological system will determine the choice of strategy of realization of heavy metal ions effect and, consequently, the biological effect itself. Which of the possible strategies will dominate, depend on the rate of changes of concentration of heavy metal ions in biological systems, functional activity of organism at the moment of metal action and on metals chemical properties. Keeping this view, the present review deals with the concept of time-based alterations of concentration of heavy metal ions (TACMI) in biological systems. On the basis of TACMI concept formation of organism resistance to metal ions action could be explained. In the event of slow increase of its concentration in organism, it produces induction of metallothioneins, other stress-proteins and relative changes in the whole metabolic system. This, first of all, results in formation of new specific epigenotypes, which provide higher resistance (hormesis effect) not only to metal ions that induced this effect, but also to such stress-factors as high temperature (at least, for micro-algae cells).

Keywords: Heavy metal ions, Hormesis, Organism resistance

 

Indian Journal of Experimental Biology

Vol 48, July 2010, pp. 697-709

 

Cellular and molecular mechanisms of dichlorvos neurotoxicity: Cholinergic, nonchlolinergic, cell signaling, gene expression and therapeutic aspects

B K Binukumar & K D Gill*

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India 160 012

 

Inappropriate use of toxic chemicals is common in developing countries, where it leads to excessive exposure and high risks of unintentional poisoning. Risks are particularly high with the pesticides used in agriculture, poor rural populations live and work in close proximity to these compounds and often store these compounds in and around their homes. It is estimated that most of the death from pesticide poisoning occur in developing countries. Organophosphate insecticides have been extensively used in agriculture in developing countries. Dichlorvos is a synthetic insecticide and belongs to a family of chemically related organophosphate pesticides (OP). Toxicity of dichlorvos has been documented in accidental human poisoning, epidemiological studies, and animal models. In this review, molecular mechanisms of dichlorvos neurotoxicity have been described. Usage, biotransformation, environmental levels, general population and occupational exposure, effects on cell signaling receptors, mitochondrial metabolism, oxidative stress and gene expression of dichlorvos have been reviewed. Assessment of acute and chronic exposures as well as neurotoxicity risk for lifetime exposures to dichlorvos have also been considered. In addition special emphasis has been given to describe, the role of dichlorvos in the chronic neurotoxicity and its molecular targets that ultimately lead to neurodegeneration.

Keywords: Behavioral, Dichlorvos, Neurotoxicity, Nicotinic receptors, Organophosphate

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 710-721

 

Effects of diesel exhaust, heavy metals and pesticides on various organ systems: Possible mechanisms and strategies for prevention and treatment

Kavita Gulati1, Basudeb Banerjee2, Shyam Bala Lall3 & Arunabha Ray1*

1Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi 110 007, India

2Department of Biochemistry University College of Medical Sciences and GTB Hospital, Delhi 110 092, India

3Formerly, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi 110 029, India

 

Environmental pollutants have a significant impact on the ecosystem and disrupt balance between environment, human and non-human components that result in deleterious effects to all forms of life. Identifying environmental factors for potential imbalance are extremely crucial for devising strategies for combating such toxic dysregulation. Automobile exhaust (in air), heavy metals (in food and water) and pesticides (in air, food, soil and water) are the most common environmental pollutants and their short and long term exposures can cause hazardous effects in humans leading to systemic disorders involving lungs, kidney and immune systems. Mechanisms involved in genesis of such toxic effects have revealed complex, interactive pathways. Strategies for the protection of homeostasis and health, viz., general preventive measures, nutritional supplements and herbal agents have been described, to counter these pollutants induced damaging effects on various body systems.

Keywords: Antioxidants, Azadirachta indica, Diesel exhaust, Environmental toxicants, Heavy metals toxicity, Oxidative stress, Pesticides

Papers

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 722-730

Altered glucose homeostasis in response to aluminium phosphide induced cellular oxygen deficit in rat

Raina Dua, Vijay Kumar, Aditya Sunkaria & K D Gill*

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India

Received 29 October 2009; revised 26 April 2010

The present study was designed to analyze the effect of acute aluminium phosphide (ALP) (10 mg/kg body wt.) exposure on the glucose homeostasis in rat liver and brain. ALP has been implicated in the inhibition of cytochrome oxidase causing reduced oxygen uptake and decreased ATP synthesis eventually resulting in cellular energy crisis. A significant decrease in plasma glucose levels in the ALP treated rats has been observed. Therefore, decreased ATP levels coupled with hypoglycemia may further intensify the cellular energy deficits. In order to meet the sudden increase in the local energy demand, the brain tissue utilizes its stored energy in the form of glycogen breakdown as observed by a decrease in the glycogen levels in both liver and brain which was accompanied by a marked increase in the activity of glycogen phosphorylase in both the tissues. The glycolytic rate was found to be enhanced in brain tissue as evident by increased activities of hexokinase and phosphofructokinase enzymes, but decreased in liver of ALP treated rats. Lactate levels were increased in plasma and brain, but decreased in liver of ALP treated rats. Pyruvate levels increased in the plasma and liver, but no change was observed in the brain tissue. ALP did not cause any change in the gluconeogenic enzymes like glucose-6-phosphatase and fructose-1,6-bisphophatase in brain, but a significant increase was observed in the liver. Results of the study showed that ALP induced cellular energy deficit leads to compromised energy status of liver and brain coupled with substantial alterations in glucose homeostasis. However, the activity of glucose-6-phosphate dehydrogenase decreased significantly in both the tissues.

Keywords: Aluminium phosphide, Fructose-1,6-bisphosphate, Glucose homeostasis, Glucose-6-phosphate

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 731-736

 

Cyanide-induced changes in the levels of neurotransmitters in discrete brain regions of rats and their response to oral treatment with a-ketoglutarate

 

Janardhanan Hariharakrishnan, Ravindra M Satpute & Rahul Bhattacharya*

Division of Experimental Therapeutics, Defence Research and Development Establishment, Jhansi Road,
Gwalior 474 002, India

Received 11 November 2009; revised 26 April 2010

Cyanide is a potential suicidal, homicidal and chemical warfare agent. It produces histotoxic hypoxia following inhibition of cytochrome c oxidase, a terminal respiratory chain enzyme. The profound metabolic changes lead to neurotoxicity including alterations in the levels of neurotransmitters. The present study addressed the effect of acute exposure of lethal and sub-lethal doses of potassium cyanide (KCN; 0.75 or 2.0 LD50; po) on the levels of neurotransmitters in discrete brain regions of rats and its response to treatment with a-ketoglutarate (a-KG; 0.5 g/kg; po; -10 min) alone or with sodium thiosulphate (STS; 1.0 g/kg; ip; -15 min). KCN significantly decreased norepinephrine, dopamine and
5-hydroxytryptamine levels in different brain regions which were resolved by
a-KG and/or STS. Corpus striatum and hippocampus were more sensitive as compared to cerebral cortex and hypothalamus. a-KG, a potential cyanide antidote alone or with STS showed neuroprotective effects against cyanide.

Keywords: Cyanide, Cyanide antidote, a-Ketoglutarate, Neurotransmitters

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 737-743

 

Microsomal Ca2+ flux modulation as an indicator of heavy metal toxicity

Srinivas Pentyala*1, Jeanine Ruggeri1, Amulya Veerraju1, Zhangzhang Yu1, Anjori Bhatia1,
Durisala Desaiah2 & Parminder Vig2

1Department of Anesthesiology, Stony Brook University Medical Center, Stony Brook, NY, USA

2Department of Neurology, University of Mississippi Medical Center, Jackson, MS, USA

Received 14 November 2009; revised 22 April 2010

Inositol 1,4,5-trisphosphatee (IP3), an intracellular messenger, releases Ca2+ from microsomes. Ca2+ plays a major role in regulating various cellular events like neural transmission and regulation of hormones and growth factors. Aluminum (Al), lead (Pb) and mercury (Hg) were reported to alter Ca2+-regulated events thereby causing neurotoxicity. Hence, an attempt was made characterize IP3 mediated Ca2+ release from rat brain microsomes under the influence of Al, Pb and Hg. Different concentrations of metals were tested over a designated time scale and their effects on IP3 mediated Ca2+ release from microsomes were monitored using Fura-2 technique. All the three metals inhibited IP3 mediated Ca2+ release, Pb being more potent. The order of potency of these three metals was Pb>Hg>Al. Except for Al, both Hg and Pb independently released Ca2+ from microsomes. Re-uptake of Ca2+ into microsomes was inhibited by all the three metals, Pb being more potent. Microsomal Ca2+-ATPase activity was also inhibited by all the three metals. These results suggest that neurotoxicity exerted by Al, Pb and Hg may be due to the interference of these metals with IP3 mediated calcium release and also interfering with the microsomal Ca2+ sequestration mechanism. Differential effects of heavy metal induced changes in
Ca2+ flux can be used as an index of relative toxicity.

Keywords: Ca2+ flux, Heavy metal toxicity, Inositol 1,4,5-trisphosphate, Microsomes

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 744-751

 

Acute and sub-acute toxicity of an insect pheromone, N-heneicosane and combination with insect growth regulator, diflubenzuron, for establishing
no observed adverse effect level (NOAEL)

Yangchen Doma Bhutia*, Anshoo Gautam, Neeti Jain, Fakhruddin Ahmed, Manoj Sharma, Ram Singh, Satish Kumar, Murlidhar Jaywantrao Mendki, Pravin Kumar & R Vijayaraghavan

Defence Research and Development Establishment, Gwalior 474 002, India

Received 18 November 2009; revised 30 April 2010

Aedes aegypti mosquito is one of the most notorious vectors of dangerous diseases like dengue hemorrhagic fever and chikangunya. One method of control of the vectors is by the use of semiochemicals or pheromones. The pheromone
n-heneicosane (C21) has been proved to be effective in attracting the female Aedes aegypti to lay eggs in the treated water and the growth of the larva is controlled by insect growth regulator diflubenzuron (DB). This study was planned to assess the safety of C21 alone and the combination with DB. Acute toxicity tests were carried out using two doses, viz., 1600 and
3200 mg/kg and two routes of exposure oral and intra-peritoneal. Dermal toxicity test was carried out in both male and female rats at the dose of 3200 mg/kg. Primary skin irritation test was carried out in rabbits. Sub-acute (90 days) dermal toxicity studies in male and female rats at the dose of 1 and 2 mg/kg via the per-cutaneous route were also studied.
Sub-acute (90 days) toxicity test through the oral route was carried out, at doses 125, 250 and 500 mg/kg in male and female rats. The calculated LD50 by ip route and dermal route was more than 5 g/kg in mouse and rats of both the sexes. In the primary skin irritation test no significant changes were noted. In the sub-acute toxicity studies even 500 mg/kg dose was not able to produce toxic response in rats when they were dosed daily for 90 days. The established no observed adverse effect level (NOAEL) was more than 500 mg/kg.

Keywords: Acute toxicity, Attracticide, Diflubenzuron, Heneicosane, Insect Growth Regulator, NOAEL, Sub-acute toxicity


 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 752-761

 

Prophylactic efficacy of combination of DRDE-07 and its analogues with amifostine against sulphur mustard induced systemic toxicity

Anshoo Gautam, Alka Gupta, Vinay Lomash, S C Pant, & R Vijayaraghavan

Defence Research and Development Establishment, Gwalior 474 002, India

Received 5 February 2010; revised 17 May 2010

Sulphur mustard, [bis (2-chloroethyl)] sulphide (SM), is a bifunctional alkylating agent. SM forms sulphonium ion in the body which alkylates DNA and several other macromolecules, and induces oxidative stress. Although several antidotes have been screened for the treatment of systemic toxicity of SM in experimental animals none of them are recommended so far. In the search for more effective and less toxic antidotes, various combinations were tried against SM induced toxicity and skin lesions. SM exposed through percutaneous route was used to evaluate the prophylactic efficacy of various combinations. Low dose of DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulphide), DRDE-30 [S-2(2-aminoethyl amino) ethyl propyl sulphide], DRDE-35 [S-2(2-aminoethyl amino) ethyl butyl sulphide] with amifostine combinations, were given orally 30 min prior to SM exposure. Significant depletion was observed in body weight, organ body weight index and hepatic GSH and GSSG content in mice after SM exposure. Pretreatment with low dose of different combinations of DRDE-07, DRDE-30 and DRDE-35 with amifostine could recover biochemical alterations and histopathological changes caused by SM exposures.

Keywords: Amifostine, Combination treatment, Cytoprotection, Cytotoxicity, Percutaneous, Sulphur mustard

 

Indian Journal of Experimental Biology

Vol. 48, July 2010, pp. 762-768

 

Sub-chronic arsenic exposure aggravates nephrotoxicity in experimental
diabetic rats

Hitesh Vashrambhai Patel & Kiran Kalia*

Laboratory of Biochemistry, BRD School of Biosciences, Sardar Patel University, V V Nagar 388 120, India

Received 16 December 2009

The present experiment was planned to study nephrotoxicity in experimental diabetic rats under sub-chronic exposure to arsenic. Alloxan induced diabetic and control rats were exposed to sodium arsenite (0 and 5.5 mg/kg, orally) for 30 days. More pronounced nephrotoxic effects were noted in arsenic exposed diabetic group as evidenced by increased blood urea nitrogen, serum creatinine and relative kidney weight and decreased level of reduced glutathione and glutathione peroxidase activity compared to non arsenic exposed diabetic group. Increased level of lipid peroxidation, protein oxidation, superoxide dismutase and catalase activities under diabetic condition remained unchanged in arsenic exposed diabetic group compared to unexposed diabetic group.

Keywords: Arsenic, Diabetes mellitus, Oxidative stress, Renal tissue