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radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
radio protectors
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radio protectors

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    • 1. RADIO PROTECTORS Ajmeera Divya*, Vijay kumar .N Department of Pharmaceutical Sciences,St. Peters Institute of Pharmaceutical Sciences, Vidyanagar, Warangal. Email: ajmeera.divya@gmail.com
    • 2. What are Radio protectors?• Radio protectors are compounds that are designed to reducethe damage in normal tissues caused by radiation.• Radio protective agents are useful in eliminating or reducingthe severity of deleterious cellular effects which are caused byexposure to internal and or external irradiation in patients orstaff personnel.
    • 3. Why Radio protectors?• Radio therapy is a common and effective tool for cancertreatment and rapid technological advancements hasincreased human exposure to ionising radiationenormously.• Ionising radiation produces free radicals in the cell thatcan induce damage to the DNA and lead to side effectsand or secondary tumors.
    • 4. • In order to protect humans against deleterious effects ofionising radiation, attempts were made as early as 1946and efforts continued to search Radio protectors whichmay be of great help for human application and effectivelyoffer protection to the normal tissues after radiationexposure during radio therapy of cancer.
    • 5. What comes under Radio protectors? Chemical Radio protectors: Agents delivered prior or at the time of irradiation with the intent of preventing or reducing damage to normal tissues.Mitigators : Agents delivered at the time or after irradiation is complete but prior to the manifestation of normal tissue toxicity. Treatments : Agents delivered to ameliorate established normal tissue toxicity .
    • 6. How do Radio protectors work?Radio protective activity is accomplished through differentmechanisms on three special levels of cell organization. Molecular level:• Free radical scavenging• Hydrogen atom donation• Bounding to critical biological targets• Forming mixed disulphide formations Physiological-biochemical level:• Hypoxsy• Loosening unpotential disulphide•Hypothermia
    • 7. Organic level:• Stimulating reparation of cell
    • 8. What are the novel approaches for Radio protectors?Mimics of antioxidant enzymes:•Sulfhydryl compounds : The most widely studied class ofcompounds is sulfhydryls containing an –SH(thiol) group thatserves to scavenge free radicals.Example: simplest sulfhydryl is the amino acid, Cysteine.Case study: Iv inj./ingestion of large doses of cysteine 1 hr. or5 min. prior to TBI protected male and female rats againstradiation injury where as injecting Cysteine 5 min. afterradiation did not protect the rats.
    • 9. •Antioxidants: acts as hydrogen atom donating reducingagents where, oxidants are neutralized by H+ atoms resultingin a less reactive or non-reactive product from originaloxidant.Example: superoxidedismutase(SOD),Catalase, Glutathione peroxidase are someof the naturally occuring antioxidants where the substratesare enzyme specific.Other anti oxidants include Ascorbic acid, Tocopherols andPoly phenols like glutathione etc.
    • 10.  Nitroxides: these are the most promising agents in clinicaltrials for future use as radio protectorsExamples: Tempol(4-hydroxy 2,2,6,6-tetra methyl piperidine-1-oxyl)- Topical application prevented the radiation inducedalopecia in guinea pig.Non-antioxidants: Increases the expession of antioxidantenzymes such as SOD, Glutathione peroxidase and Glutathionereductase.Example: Melatonine
    • 11. Growth factors: Many cytokines and growth factorsthat stimulate the differentiation of stem cell s.Example: KGF-a growth factor that stimulates a no. ofcellular processes like cell differentiation, cellproliferation, DNA repair and detoxification of reactiveoxygen species.Gene therapy: Palifermin- a recombinant human KGFapproved for use in redusing the incidence and durationof severe oral mucosistis in patients with hematologicalmalignancies who receive high doses of chemotherapyand radiation therapy followed by stem cell rescue.
    • 12. Natural products: Non-toxic and proven therapeuticbenefits.Example: Mint, Green tea.
    • 13. Radio protectors in clinical use?• Amifostine (WR-2721) is the only drug approved by FDAas a Radio protector- for prevention of radiation induceddamage to salivary glands• Because of higher activity of membrane bound alkalinephosphatase and high PH of the normal tissue, differentialsparing occurs within minutes of administration.•The possible draw backs including dose limiting toxicitylike hypotension, nausea and vomiting have reduced its usein clinic
    • 14. •WR-2721 is a prodrug ,dephosphorylated to the activespecies, WR- 1065 which is very rapidly taken up andaccumulates in normal tissues, slow in tumors.
    • 15. Need for further studies?• In cancer care, ensuring that the right dose of radiationtargets the tumor without damaging neighboring cells is of utmost importance.• Present agents are associated with dose limiting toxicities.• There is continued interest and need for identification and development of non-toxic and effective radio protective compounds.
    • 16. References•Savoye C, Swenberg C, Hugot S, et al. Thiol WR-1065 anddisulphide WR-33278, two metabolitesof the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage. Int J Radiat Biol. 1997; 71:193–202.[PubMed: 9120355].• Kouvaris JR, Kouloulias VE, Vlahos LJ. Amifostine: The firstselective-target and broad-spectrum radioprotector. The Oncologist.2007; 12:738–747. [PubMed: 17602063].
    • 17. • Schuchter LM, Hensley ML, Meropol NJ, et al. 2002 update ofrecommendations for the use of chemotherapy and radiotherapyprotectants: Clinical practice guidelines of the American Societyof Clinical Oncology. J Clin Oncol. 2002; 20:2895–2903.[PubMed: 12065567].•Hensley ML, Hagerty KL, Kewalramani T, et al. AmericanSociety of Clinical Oncology 2008 clinical practice guidelineupdate: Use of chemotherapy and radiation therapy protectants.J Clin Oncol. 2009; 27:127–145. [PubMed: 19018081].
    • 18. •Brizel DM, Overgaard J. Does amifostine have a role inchemoradiation treatment? Lancet Oncol. 2003; 4:378–381.[PubMed: 12788413] .
    • 19. Thank you

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