1. RADIO PROTECTORS
Ajmeera Divya*, Vijay kumar .N
Department of Pharmaceutical Sciences,
St. Peter's Institute of Pharmaceutical Sciences,
Vidyanagar, Warangal.
Email: ajmeera.divya@gmail.com

2. What are Radio protectors?
• Radio protectors are compounds that are designed to reduce
the damage in normal tissues caused by radiation.
• Radio protective agents are useful in eliminating or reducing
the severity of deleterious cellular effects which are caused by
exposure to internal and or external irradiation in patients or
staff personnel.

3. Why Radio protectors?
• Radio therapy is a common and effective tool for cancer
treatment and rapid technological advancements has
increased human exposure to ionising radiation
enormously.
• Ionising radiation produces free radicals in the cell that
can induce damage to the DNA and lead to side effects
and or secondary tumors.

4. • In order to protect humans against deleterious effects of
ionising radiation, attempts were made as early as 1946
and efforts continued to search Radio protectors which
may be of great help for human application and effectively
offer protection to the normal tissues after radiation
exposure 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 .

7. How do Radio protectors work?
Radio protective activity is accomplished through different
mechanisms 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

8. Organic level:
• Stimulating reparation of cell

9. What are the novel approaches for Radio protectors?
Mimics of antioxidant enzymes:
•Sulfhydryl compounds : The most widely studied class of
compounds is sulfhydryls containing an –SH(thiol) group that
serves to scavenge free radicals.
Example: simplest sulfhydryl is the amino acid, Cysteine.
Case study: Iv inj./ingestion of large doses of cysteine 1 hr. or
5 min. prior to TBI protected male and female rats against
radiation injury where as injecting Cysteine 5 min. after
radiation did not protect the rats.

10. •Antioxidants: acts as hydrogen atom donating reducing
agents where, oxidants are neutralized by H+ atoms resulting
in a less reactive or non-reactive product from original
oxidant.
Example: superoxide
dismutase(SOD),Catalase, Glutathione peroxidase are some
of the naturally occuring antioxidants where the substrates
are enzyme specific.
Other anti oxidants include Ascorbic acid, Tocopherols and
Poly phenols like glutathione etc.

11.  Nitroxides: these are the most promising agents in clinical
trials for
future use as radio protectors
Examples: Tempol(4-hydroxy 2,2,6,6-tetra methyl piperidine-
1-oxyl)- Topical application prevented the radiation induced
alopecia in guinea pig.
Non-antioxidants: Increases the expession of antioxidant
enzymes such as SOD, Glutathione peroxidase and Glutathione
reductase.
Example: Melatonine

12. Growth factors: Many cytokines and growth factors
that stimulate the differentiation of stem cell s.
Example: KGF-a growth factor that stimulates a no. of
cellular processes like cell differentiation, cell
proliferation, DNA repair and detoxification of reactive
oxygen species.
Gene therapy: Palifermin- a recombinant human KGF
approved for use in redusing the incidence and duration
of severe oral mucosistis in patients with hematological
malignancies who receive high doses of chemotherapy
and radiation therapy followed by stem cell rescue.

13. Natural products: Non-toxic and proven therapeutic
benefits.
Example: Mint, Green tea.

14. Radio protectors in clinical use?
• Amifostine (WR-2721) is the only drug approved by FDA
as a Radio protector- for prevention of radiation induced
damage to salivary glands
• Because of higher activity of membrane bound alkaline
phosphatase and high PH of the normal tissue, differential
sparing occurs within minutes of administration.
•The possible draw backs including dose limiting toxicity
like hypotension, nausea and vomiting have reduced its use
in clinic

15. •WR-2721 is a prodrug ,dephosphorylated to the active
species, WR- 1065 which is very rapidly taken up and
accumulates in normal tissues, slow in tumors.

16. Need for further studies?
• In cancer care, ensuring that the right dose of radiation
targets 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.

17. References
•Savoye C, Swenberg C, Hugot S, et al. Thiol WR-1065 and
disulphide WR-33278, two metabolites
of 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 first
selective-target and broad-spectrum radioprotector. The Oncologist.
2007; 12:738–747. [PubMed: 17602063].

18. • Schuchter LM, Hensley ML, Meropol NJ, et al. 2002 update of
recommendations for the use of chemotherapy and radiotherapy
protectants: Clinical practice guidelines of the American Society
of Clinical Oncology. J Clin Oncol. 2002; 20:2895–2903.
[PubMed: 12065567].
•Hensley ML, Hagerty KL, Kewalramani T, et al. American
Society of Clinical Oncology 2008 clinical practice guideline
update: Use of chemotherapy and radiation therapy protectants.
J Clin Oncol. 2009; 27:127–145. [PubMed: 19018081].

19. •Brizel DM, Overgaard J. Does amifostine have a role in
chemoradiation treatment? Lancet Oncol. 2003; 4:378–381.
[PubMed: 12788413] .

20. Thank you