EXPERIMENTAL PHARMACOLOGY LABORATORY

The main objective of this laboratory has been to create/develop, standardize and use new models as aid to pharmacology experimentation. Laboratory has developed and used several models for cardiovascular, genitourinary and respiratory systems pharmacology. Currently, main thrust of the laboratory is investigations on various therapeutic agents against cardiomyopathy, cardiac fibrosis and lung injury in sepsis and their repurposing. Repurposing potential of pravastatin and canagliflozin was investigated in the isoprenaline-induced cardiac fibrosis and further their signaling mechanisms were also explored. In addition, niclosamide (antiparasitic drug) and orlistat (antiobesity drug) were also investigated for their repositioning against the cardiac fibrosis. Apart from this, atorvastatin alongwith imipenem drugs were investigated against the sepsis-induced vascular dysfunctions and acute lung injury. These drugs have shown beneficial effect against the sepsis-induced lung injury as well as the vascular dysfunctions and increased the survival time in the laboratory animals. Further, investigation of plants-based therapeutics against LPS-induced acute lung injury is another thrust area of the laboratory. Currently, investigation against the two plants namely Terminalia chebula (Haritaki) and Vitex negundo (Nirgundi) are going on against the LPS-induced acute lung injury in the laboratory model with the aim to find out the ameliorating potential of these plants against the lung injury. Previously, laboratory also investigated role of β1-adrenergic receptor signaling in the mouse model of sepsis in respect to atorvastatin.

Thematic area of lab

• Cardiovascular and Respiratory Pharmacology
• Lung Injury
• Sepsis

Infrastructure and facility in lab

• ELISA Reader
• Western blot Assembly
• Organ Bath System
• Data Acquisition system for organ bath

Major Achievement of Lab

• The phasic component of K+-free contracture in urinary bladder was shown to be mediated by the participation of receptor-operated calcium channels and the tonic component was mediated by mobilization of extracellular Ca2+ through voltage-gated Ca2+ channels.
• Voltage-dependent Ca2+ channels and membrane K+ channels have functional role in generating spontaneous contractions in rat portal vein
• Hypothyroid state in rats was shown to alter the functional characteristics of voltage-gated Ca2+ channels in rat uterine smooth muscle
• Atorvastatin pretreatment in sepsis was shown to significantly improve the survival time and acute lung injury in mice
• P1-purinoceptors were identified in pre- and post-ganglionic cholinergic nerve fibers in chick oesophagus
• Pre-treatment of Dalbergia sissoo leaf extract improved the myocardial injury in rats
• Demonstrated that NO and EDHF significantly contributed to TRPV4 channel-mediated endothelium-dependent relaxation of the rat pulmonary artery.
• Kaempferol pre-treatment showed attenuation in lipid profile, infarcted area and oxidative stress in ISP-induced myocardial injury in rats
• Biochanin-A showed attenuation in the isoprenaline-induced cardiac fibrosis in mice model
• Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat isolated pulmonary artery
• Biochanin-A showed relaxation in goat coronary artery in endothelium-independent pathways and showed the partial involvement of KATP channels, protein kinase A and estrogen receptors and full involvement of Cav1.2 channels.
• Luteolin alleviates vascular dysfunctions in CLP‑induced polymicrobial sepsis in mice
• Repurposing potential of pravastatin, canagliflozin (SGLT2 inhibitor), niclosamide (antiparasitic) drug against isoprenaline-induce cardiac fibrosis was investigated.

List of projects going on in lab

• Therapeutic evaluation of nano-encapsulated Vitex negundo extract against lung injury (PI: Dr. Meemansha Sharma; Start date: Jan, 2025; End date: Dec, 2027; Project type: Institute; Funding agency: ICAR-IVRI)

Name and contact details of Lab in-charge

• Dr. T.U. Singh Senior Scientist Division of Pharmacology and Toxicology ICAR-IVRI, Izatnagar-243122, Uttar Pradesh Office: 0581-2300291 Mobile: 9412445843 tusingh80@gmail.com

INDIGENOUS DRUGS LABORATORY

The Indigenous Drugs (ID) laboratory is one of the main laboratories of this division since its inception in 1976. This lab deals with the screening of plants against animal diseases. Preparation of different types of plant extracts and separation of essential oils are among the routine activities in this lab. Different extracts of several medicinal plants have been prepared and screened for various activities and many bioactive phytoconstituents have been isolated in the early years. The patents filed (three) and formulation prepared (many) have crucial role of this laboratory. Currently, some herbal products are being screened for their wound healing potential.

Thematic area of lab

• Pain and inflammation
• Wound repair and regeneration

Infrastructure and facility in lab

• Gradient thermal cycler
• Rota vaccum evaporator
• Facility for making plant extract and isolation of essential oils

Major Achievement of Lab

• Patent granted for a process of preparing herbal composition for the treatment of mange in animals
• Patent granted for a herbal formulation for the treatment of haemonchosis in sheep
• Patent application has been filed for a process for preparing an indigenous drug formulation for the treatment of diarrhoea in animals
• Products such as Mangol, Mange cure, Ringworm cure, burn cure, Diarrhoea cure, and anti-haemonchosis formulation for sheep have been developed
• The clinical evaluation of a herbal ointment for healing efficacy was undertaken in natural cases of cutaneous wounds in pigs and it displayed potential to be developed as a technology
• Icariin improved cutaneous wound healing in normal and diabetic rats due to its angiogenic and MMPs modulatory activity
• Hydroethanolic extract of Limonia acidissima L. unripe fruit pulp powder protects against dextran sulfate sodium-induced ulcerative colitis in mice.
• Protective effect of Limonia acidissima L. fruit (Wood apple/Kaith bel) sap was observed against capsaicin-induced colonic injury in mice
• Isolated goat reticular groove behaved differently to classical neurotransmitters. Senna (C. angustifolia) extract produced contractile effect, while essential oil of bottle brush (Callistemon sp.) produced relaxation in isolated reticular groove preparation.
• Essential oils extracted from medicinal plants namely EOIVR-2 and EOIVR-3 (coded), respectively produced paralysis in Gastrophylax crumenifer in spastic and flaccid manner.

List of projects going on in lab

• A confirmatory preclinical study to assess the healing potential of some promising herbal preparations in cutaneous wound model in guinea pigs. (Principal Investigator: Dr. Anshuk Sharma; Start date: Aug, 2022; End date: July, 2025; Project type: Institute; Funding agency: ICAR-IVRI)
• Exploring the therapeutic potential of Limonia acidissima L. unripe fruit pulp in mouse models of capsaicin-induced visceral pain and dextran sulphate sodium-induced colitis (Principal Investigator: Dr. Anshuk Sharma; Start date: September, 2023; End date: August, 2025; Project type: Institute; Funding agency: ICAR-IVRI)

Name and contact details of Lab in-charge

• Dr. Anshuk Sharma, Scientist Division of Pharmacology and Toxicology IVRI, Izatnagar-243122, Uttar Pradesh Contact details: 0581-2300291 Mobile: +91-8367894336 Email ID: anshuks15@gmail.com

CHEMOTHERAPY LABORATORY

Main emphasis of the research work in this laboratory has been to screen anthelmintic, anti-diarrhoeal and wound healing activities of herbal products. Two patent applications have been filed jointly from this and Indigenous drugs laboratory. Currently, research work is being carried out to identify and validate therapeutic targets for reproductive abnormalities particularly uterine dysfunctions during pregnancy.

Thematic area of lab

• Reproductive Immunopharmacology
• Chemotherapy

Infrastructure and facility in lab

• Cell culture facility
• Magnetic-activated cell sorter
• Organ bath with data acquisition system

Major Achievement of Lab

Intellectual property (IP) disclosures

• A fresh latex-based wound healing preparation
• A natural latex-based wound healing formulation

Research findings:

• Elevated expression and reduced phosphorylation of uterine RIG-I protein is observed in a murine model of pathogenic preterm labor.
• Leptin decreases the transcription of BKCa channels and Gs to Gi protein-ratio in late pregnant rat uterus.
• ObRb receptor, nitric oxide, and BKCa channel signaling pathways are involved in leptin-induced relaxation of pregnant mouse uterus.
• TXA2 mediates LPA1-stimulated uterine contraction in late pregnant mouse.
• Fat augments leptin-induced uterine contractions by decreasing JAK2 and BKCa channel expressions in late pregnant rats.
• Leptin receptor stimulation in late pregnant mouse uterine tissue inhibits spontaneous contractions by increasing NO and cGMP.
• Casein kinase 2 inhibition impairs spontaneous and oxytocin-induced contractions in late pregnant mouse uterus.
• Lysophosphatidic acid enhances PGE2 to PGF2α ratio and nitric oxide level in nonpregnant buffalo uterus.
• Hypercholesterolemia impairs oxytocin-induced uterine contractility in late pregnant mouse.
• Study of lysophosphatidic acid receptors (LPARs) in buffalo uterus demonstrated upregulation of LPAR1 and LPAR6 in early pregnancy.

List of projects going on in lab

• Targeting RIG-I protein in pathogenic abortions and preterm labor (Start date: Sep, 2023; End date: Sep, 2026; Funding agency: DBT; Principal Investigator: Dr. Subhashree Parida).
• Elucidation of the role of leptin signaling in macrophage switching and its therapeutic exploitation in pathogenic abortions and preterm labor (Start date: Dec, 2023; End date: Dec, 2026; Funding agency: ICMR; Principal Investigator: Dr. Subhashree Parida).

Name and contact details of Lab in-charge

• Dr.Subhashree Parida , Senior Scientist Division of Pharmacology and Toxicology ICAR-IVRI, Izatnagar-243122, Uttar Pradesh Contact details: 0581-2300291 Mobile: +91-9411917842 Email ID: subhaparida1210@gmail.com

BIOPHARMACEUTICS LABORATORY

Pharmacokinetics, pharmaceutics and screening of indigenous agents for central nervous system effects have been major activities of this laboratory. Classical Pharmacology equipment such as tail flick analgesiometer, hot plate analgesiometer, electroshock seizure unit are housed in this lab along with molecular biology equipment such as electrophoresis units, blotting apparatus, microplate washer. Several plant derived products such Caesalpinia bonducella extract, Entada pursaetha extract, Eugenia jambolana flavonoids, betulinic acid, and ursolic acid have been screened for their analgesic, antipyretic and anti-inflammatory activities. Further, synthetic agents like atorvastatin, NSAIDs, iNOS inhibitors, N-acetyl-l-cysteine, S-methylisothiourea, and PRE-084 have been investigated for various kinds of pharmacological effects. Pharmacological manipulation of chronic kidney disease is the present research area in this laboratory.

Infrastructure and facility in lab

• Tail flick analgesiometer
• Microplate washer
• Electrophoresis and blotting apparatus

Major Achievement of Lab

Many indigenous and synthetic agents were evaluated for their analgesic and anti-inflammatory properties in different animal disease models of pain and inflammatory conditions including neuropathic pain, osteoarthritis, colitis, paw oedema, sepsis, liver injury and chronic kidney disease.

• Caesalpinia bonducella seed kernel extract exhibited antipyretic and antinociceptive activities in rodents.
• Entada pursaetha stem extract was found to pose protective effect on acute hepatotoxicity, colitis, endotoxemia, osteoathritic pain in rodents via anti-inflammatory and antioxidant activities.
• Atorvastatin, a HMG-CoA reductase inhibitor, exhibited antihyperalgesic and anti-inflammatory effects in rodent osteoarthritis and neuropathic pain.
• N-acetyl-l-cysteine, a medication used to treat paracetamol overdose was found to alleviate neuropathic pain in rats.
• Local up-regulation of NO is involved in the production and maintenance of neuropathic pain.
• S-methylisothiourea, an iNOS inhibitor ameliorated hepatotoxicity and improved neuronal injury and osteoathritisin vitro and in vivo.
• Eugenia jambolana derived compounds [Trimeric Myricetin Rhamnoside and kaempferol-7-O-α-L-rhamnopyranoside]-4’-O-4’-[kaempferol-7-O-α-L-rhamnopyranoside (EJ-01),] showed anti-nociceptive and anti-inflammatory effects in rodent paw edema model.
• Betulinic acid, a triterpenoid was found to improve kidney injury and the survival time in septic animals.
• Ursolic acid, a triterpenoid found in apple peel alleviated neuropathic pain by decreasing the pro-inflammatory mediators and inhibition of oxidative stress in rats.
• PRE-084, a selective sigma-1 receptor agonist reduced extracellular matrix deposition by reducing acquisition of profibrotic characters in the rat model of chronic kidney disease.

List of projects going on in lab:

• Investigating the efficacy of a triterpenoid, betulinic acid in age-related nephropathy (PI: Dr. Madhu CL; Start date: Sep, 2023; End date: Aug, 2025; Project type: Institute; Funding agency: ICAR-IVRI)

Name and contact details of Lab in-charge

• Dr. Madhu C L, Division of Pharmacology and Toxicology ICAR-IVRI, Izatnagar-243122, Uttar Pradesh Office: 0581-2300291 Mobile#: +91-9760016589; maddyvet@gmail.com

TOXICOLOGY LABORATORY

Safety evaluation of xenobiotics and to suggest suitable measures to combat the toxicity and to develop therapeutic agents for various types of poisons is the aim of toxicology laboratory. The main focus area of research currently is to investigate the potential toxic effects of various toxicants viz. arsenic, lantana, ethion, etc. on different biological systems such as cardiovascular, hepatobiliary system and reproductive system. Research on various toxicants like cadmium, arsenic, anilofos, malathion, chlorpyriphos, endosulfan, sumithion, phenthoate, permethrin, cypermethrin, deltamethrin, fenvalerate, and isoproturon was conducted during the previous years. Various research articles were published in reputed journals like toxicology, archives of environmental contamination and toxicology, environmental toxicology, toxicology and applied pharmacology, food and chemical toxicology, chemico biological interactions, archives of toxicology, etc.

Thematic area of lab

• Cardiovascular toxicology
• Developmental toxicology
• Reproductive toxicology
• Metals, Pesticides, and Plant toxicity studies

Infrastructure and facility in lab

• Langendorff system
• UV Visible spectrophotometer
• Refrigerated centrifuge

Major Achievement of Lab

• Phenthoate, an organophosphorus compound was found to have less cumulative effect as compared to chlorinated hydrocarbon insecticides. It seemed to have direct correlation between hypothermia and cholinesterase inhibition. The relationship of temperature and cholinesterase enzyme in blood can help as a diagnostic tool for organophosphate poisoning in animals.
• Hypothermic response after phenthoate administration was not observed in domestic fowls unlike mammals suggesting species variation in acute OP poisoning symptoms.
• Oral LD50 of deltamethrin in rats and mice was 9.36 and 20.15 mg/kg, respectively.
• Acute oral LD50 values of fenvalerate in rats and mice were found to be 149.96 and 196.43 mg/kg respectively. The pyrethroid did not have any adverse effect on reproductive and gastro-intestinal smooth muscles.
• Long term administration (7 wks and 10 wks) of isoproturon, a phenylurea herbicide produced toxicity in epididymis and testes.
• Cadmium was found to cause cytotoxicity in concentrations more than 5 μM and arsenic caused cytotoxicity at concentrations more than 10 μM in Vero cells.
• Concurrent exposure to binary mixture of arsenic and cadmium in Vero cells increased the oxidative stress compared to cadmium alone exposure, on the other hand, the apoptotic potential of cadmium was not altered by arsenic treatment rather arsenic produced necrosis at higher concentrations instead of apoptosis
• Concurrent exposure to arsenic and cadmium was found to cause cytolethality which might relate to arsenic-mediated aggravation of decrease in mitochondrial membrane potential and subsequent induction of more apoptosis in Vero cells.
• Arsenic was found to aggravate the pathogenesis of painful inflammatory conditions and reduce the therapeutic efficacy of ketoprofen in chronically arsenic-exposed subjects.
• Diltiazem HCl, a calcium channel blocker showed a protective effect to rats from cadmium-induced toxicity.
• Toxicodynamic interactions of arsenic with anilofos, malathion, chlorpyriphos, endosulfan or ochratoxin was determined.
• Atorvastatin and Candesartan ameliorated arsenic-induced cardiovascular toxicity
• Ursodeoxycholic acid treatment partially attenuated hepatotoxic changes in experimentally induced acute and subacute lantana poisoning in Guinea pigs
• Gestational exposure to ethion, an OP pesticide, caused maternal, foetal, and postnatal reproductive toxicity in rats.

List of projects going on in lab

• Understanding the foetal programming of testicular lipid metabolism caused by intrauterine exposure to ethion and its modulation by green synthesized zinc oxide nanoparticles (Start date: Mar, 2025; End date: Mar, 2028; Funding agency: ICMR; Principal Investigator: Dr. Aneesha VA)
• Assessment of herbal preparations against aflatoxicosis in broiler chicken (Start date: Jan, 2025; End date: Dec, 2027; Funding agency: ICAR-IVRI; Principal Investigator: Dr. Aneesha VA)

Name and contact details of Lab in-charge

• Dr. Aneesha V A Scientist Division of Pharmacology and Toxicology ICAR-IVRI, Izatnagar Mob. No. 9536508085 Email: draneeshava@gmail.com; aneesha.va@icar.gov.in

FOOD SAFETY LABORATORY

Established in the year 2010, this laboratory involves in analysing veterinary drug residues and environmental contaminants in animal source foods. This laboratory functioned as a lead centre for the ICAR funded Outreach Programme on “Monitoring of Drug Residues and Environmental Pollutants”. The main objective of this programme was to monitor the residues of drugs and environmental contaminants and Food Safety Laboratory coordinated the overall activities of the 14 collaborating centres spread across the country. Now this laboratory is acting as a lead center for the All India Network Programme on ‘Livestock and Poultry Products Safety. Lack of data on occurrence of residues in the animal source foods in India has prompted to initiate a project on this aspect. Having our own standards will help exporters to fetch high value for the animal source food, policy makers, to educate livestock farmers to have good animal husbandry practices, veterinary drug approving authorities, to make policy on drug approval and consumers to know about the quality of animal source foods. Further, if occurrence of a particular residue in animal product is less, we can reduce the tolerance limits and it will prevent the import of such goods and preserve the markets domestic products.

Thematic area of lab

• Veterinary drug residues
• Environmental contaminants

Infrastructure and facility in lab

• Liquid Chromatograph- Tandem Mass Spectrometer (LC-MS/MS)
• Ultra High Performance Liquid Chromatograph (UHPLC)
• High Performance Liquid Chromatograph (HPLC)
• Nitrogen Evaporator

Major Achievement of Lab

• Developed 17 HPLC and 8 GC methods for analysing different drug and pesticide residues
• A spore enzyme-based assay on paper strip was developed for detection of different groups of antibiotic residues in milk
• Monitored 3213 buffalo meat samples from Eastern & Western U.P. for various antibacterial drugs (Sulphadrugs, Fluoroquinolones and Tetracyclines: 2376 samples), anthelmintics (Albendazole and Fenbendazole, 1321 Samples) and Diminazine aceturate (206 samples).
• Monitored of 9452 poultry meat samples from Tamil Nadu, W.Bengal, Kumaon-Garwal and Jabalpur area for antibacterial drugs and pesticides residues
• 1411 poultry egg samples from West Bengal, Kumaon-Garwal and Mumbai region were monitored for antibacterials and pesticides.
• A total of 16968 milk samples collected from different parts of Karnataka, Jabalpur, Bihar, Jharkhand, Gujarat, Haryana, Punjab, Delhi, Uttar Pradesh and Rajasthan were monitored for presence of antibacterial, pesticide and heavy metal residues.
• Residues of antibacterial, pesticides and anthelmintics were determined in 3644pork samples collected from Assam and Meghalaya.
• Monitoring of residues of antibacterials, pesticides and heavy metals was done in 2013 goat meat samples collected from 25 districts of W. Bengal and two districts of Gujarat and Ranchi.
• 3171 fish samples from Mumbai-Konkan region and Guntur, Krishna and west Godavari districts of A.P. were monitored for residues of antibacterial and heavy metals.
• A total of 801 feed and fodder samples collected from 12 districts of Kumaon- Gahrwal, 8 districts of Karnataka and various parts of Delhi, Haryana and Uttar Pradesh were analysed for pesticides, heavy metals and aflatoxin B1.
• An in-house workshop on “Sampling Plan for Residue Monitoring in Animal Products” was conducted between 12th and 13th December, 2018.

List of projects going on in lab

• All India Network Programme on ‘Livestock and Poultry Products Safety’ (Project Coordinator: Dr. T.U. Singh; Principal Investigator: Dr. A.G. Telang; Start date: April, 2021; End date: March, 2026; Funding agency: ICAR)

Name and contact details of Lab in-charge

• Dr A.G.Telang, Principal Scientist& In-charge, FSL & PI, OP-MDR&EP CADRAD, IVRI, Izatnagar-243122, Uttar Pradesh avinash.telang@icar.gov.in agtelang@rediffmail.com