BY

MUHAMMAD BELLO GUSAU (MNSBMB)

OF

DEPARTMENT OF AUTHORIZATION & ENFORCMENT

Radioprotective Effect of Vitamin C (L-Ascorbic Acid) and Some Myriad Enzymes

Highlights

Aim of the StudyBackgroundBiological Effect of Ionizing RadiationScavenging Effect of L-Ascorbic Acid (Vitamin C)Side Effect of Vitamin CRadioprotective Effect of Glutathione and

Myriad EnzymesConclusionAcknowledgement References

Aim of the Presentation

The aim of the presentation is to learn the radioprotective effect of Vitamin C/Glutathione and some free radical scavengers .

Background

Radiation exist ubiquitously in the environment since the Earth’s creation in soil, water and plants.Radiation exposure is a concern in the health industry and other occupations in the world. Elevated radiation levels have been detected following Chernobyl and Fukushima Daiichi accidents on April 1986 and March 2011 respectively. This raised the need for finding out efficient and reliable RADIOPROTECTORS especially when a whole nation is exposed at high or low levels for a long period

Background Vitamin C or L-ascorbic acid, or simply

ascorbate (the anion of ascorbic acid), a water soluble vitamin is an essential nutrient for humans and certain other animal species

The name 'vitamin C' always refers to the L-enantiomer of ascorbic acid and its oxidized forms

Ascorbic acid is a weak sugar acid structurally related to glucose. In biological systems, ascorbic acid can be found only at low pH, but in neutral solutions above pH 5 is predominantly found in the ionized form, ascorbate.

Background

The biological role of ascorbate is to act as a reducing agent, donating electrons to various enzymatic and a few non-enzymatic reactions. The one- and two-electron oxidized forms of vitamin C, semidehydroascorbic acid and dehydroascorbic acid, respectively, can be reduced in the body by glutathione and NADPH-dependent enzymatic mechanisms. The presence of glutathione in cells and extracellular fluids helps maintain ascorbate in a reduced state.

Background

Mechanism of Biological Damage by Ionizing Radiation

Direct damage to DNAIndirect damage via formation of reactive chemical species

End Result: disruption cell membrane integrity, cellular chemistry and DNA replication.

Biological Damage by Direct Mechanism

• Ionizing event that occurs in nuclear DNA can break single or double strands. • Damage may be (a) irreparable, or may be (b) incorrectly repaired. • Can result in (a) cell death at next mitosis or (b) point mutation.

Direct Radiation Damage

Particle or EMR hits the DNA in the nucleus of a replicating cell, either causes the cell to die during mitosis, or induces a mutation

Biological Damage by Indirect Mechanism

• Ionizing radiation produces free electrons in materials, and thus ion pairs. • Ion pairs combine to form reactive chemical species. • Reactive chemical species disrupt cell membrane integrity, cellular chemistry and DNA replication.

Radioprotective Effect of Vitamin C

As seen earlier the effects of radiation are caused mainly by the generation of reactive oxygen species (ROS). These ROS interact with biological molecules producing toxic free radicals leading to lipid peroxidation and DNA damage

Lipid peroxidation has effects on biological membranes and studies on lipid peroxidation can provide important information about detrimental effects of gamma-radiation.

Radioprotective Effect of Vitamin C

ROS can also alter the balance of endogenous protective systems, such as glutathione and enzymatic antioxidants (SOD, CAT and GPx) defence system, thus the endogenous antioxidant defences are inadequate to reduce the radiation induced free radicals.

Appropriate antioxidant intervention may inhibit or reduce free radical toxicity and thus offer protection against radiation. Several dietary anti-oxidants have been reported to decrease free radical attack on biomolecule.

Radioprotective Effect of Vitamin C

Numerous studies have examined the radioprotective effect of antioxidant free radical scavengers, which protect the cell and its organic constituent molecules from free radicals damage

Vitamin C have been reported to be an effective antioxidant and free radical scavenger and, in vivo and in vitro conditions, reduce oxidative and free radical-induced damage to DNA and membranes in biological systems

Vitamin C is an important dietary factor that has been reported to decrease the adverse effect of ROS and RNS by scavenging radicals or by neutralizing an array of these radicals.

Radioprotective Effect of Vitamin C

Vitamin C functions as a free radical scavenger of active and stable oxygen radicals as have been shown to protect several biological systems against ionizing radiation. The radioprotective effect of L-ascorbic acid seems to be due to its interaction with radiation-induced free radicals

Radio protective Effect of Glutathione and Other Myriad Enzymes

Glutathione also known as Gamma-L-Glutamyl-L-Cysteinylglycine is a substance produced naturally by the liver. It is also found in fruits, vegetables, and meats.People take glutathione by mouth for treating cataracts and glaucoma, preventing aging, treating or preventing alcoholism, asthma, cancer, heart disease (atherosclerosis and high cholesterol),hepatitis, liver disease, diseases that weaken the body’s defense system and chronic fatigue syndrome, memory loss, Alzheimer’s disease, osteoarthritis, and Parkinson’s disease. Glutathione is also used for maintaining the body’s defense system (immune system) and fighting metal and drug poisoning

Structure

Radioprotective Effect of Glutathione

Among the functions of glutathione is its role as free radical scavenger of active and stable oxygen radicals as have been shown to protect several biological systems against ionizing radiation

Glutathione and Myriad Enzymes

Glutathione and Myriad Enzymes

Scavenging Effect of Myriad Enzymes

Conclusion

The radioprotective and mitigative effects of Vitamin C and Myriad Enzymes against cellular damage caused by ionizing radiation and oxidative stress has been proven to play a pivotal role in a situation where the effects of ionizing radiation are to be controlled.

Acknowledgement

Special thanks are due to Department of Biochemistry and Medical Laboratory Department of Usmanu Danfodiyo, University, Sokoto for their academic and practical equipment support

Gratitude is expressed to my able Director and his assistant in the persons of Dr. Yau Idris and Mr. Tukur A. Faru for their guidance, directions and moral support

Special thanks to DRS who indirectly but tremendously contributed to this seminar

Gratitude is also expressed to DAF for moral supportMy profound gratitude to all the people present here.

References

El-Habit OH, Saada HN, Azab KS, Abdel-Rahman M, El Malah DF. The modifying effect of β-carotene on gamma radiation induced elevation of oxidative reactions and genotoxicity in male rats. Mutat Res 2000;466:179-86

El-Nahas SM, Mattar FE, Mohammed AA. Radioprotective effect of Vitamin C and E. Mutat Res 1999; 301:143-7

Mallikarjun Rao KV, Jagetia GC, Ascorbic Acid treatment enhances the wound healing in mice exposed to radiation. Indian J Radiat Res 2004;1:24

References

Maurya DK, Devasagayam TP, Nair CK. Some novel approaches for radioprotection and the beneficial effects of natural products. Indian J Exp Biol 2006;44:93-114

Naidu KA. Vitamin C in human health and disease is still a mystery? An Overview. Nutr J 2003;2:7-17

Tarladacalisir YT, Kanter M, Uygun M. Protective effects of vitamin C on cisplatin-induced renal damage: a light and electron microscopic study. Ren Fail 2008;30:1-8

Reference

Weiss JF, Kumor KS, Walden TL. Advances in radio-protection through the use of combined agent regiments. Int J Radiat Biol 1998; 57:709-22

Wilson RL. Free radical repair mechanisms and the interaction of glutathione and vitamin C and E. In: Nyga OF, Simic MG, editors. Radioprotectors and anticarcinogens. NewYork: Academic Press; 1983. p.1-23.