freeradicals pharmacology

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1. FREE RADICAL P H A R MACOLOGY B y - S . P SUBMITTED TO :- ASSO C PROF: DR SANJIV KARALE DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY SUBMITTED BY:- THEERTHA T M PHARM (IST YEAR) SREE DEVI COLLEGE OF PHARMACY

2. Free Radicals : Introduction A free radical is a species containing one or more unpaired electrones Free radicals are electron deficient species,but they are usually uncharged , so their chemistry is very different from the chemistry of even electron deficient species such as carbocations and carbenes These unpaired electrones readily form free radical molecule which are chemically reactive and highly unstable

3. 1. superoxide,02- 2.Hydrogen peroxide,H2O2 3.Hydroxyl radical, OH- 4.single oxygen,1O2 5.Hydroperoxy radical,HOO - 6.lipid peroxide radical,ROO - 7.Nitric oxide, NO-

4. Reactive oxygen species  (ROS) are chemically  reactive  chemical  species  containing  oxygen . Examples include peroxides, superoxide, hydroxyl radical, singlet  oxygen , and alpha- oxygen Reactive oxygen species (ROS)

5. Generation of free radicals Normally, bonds don’t split to leave a molecule with an odd,unpaired electron.but when week bond split ,free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. When the attacked molecule loses its electron , it becomes a free radiacal itself ,beginning a chain reaction. All this happens in nanoseconds Once the process is started, it can cascade ,finally resulting in the disruption of a living cell. Some free radicals may arise normally during metabolism and by immune system cells purposefully to neutralize viruses and bacteria .normally the body can handle free radicals, but if antioxidants are unavailable or if the free radicals production becomes excessive ,damage can occur

6. Factors responsible for the formation of free radicals Cellular metabolism Environmental effects About 1-4% of oxygen taken up in the body is converted to free radicals. They are constantly produced during the normal oxidation of foodstuffs Due to leaks in the electron transport chain in mithocondria Some enzymes such as xanthine oxidase and aldehyde oxidase form superoxide anion radical or hydrogen peroxide Due to drug metabolism Due to damages causes by uv or x ray Cigaratee or alcohol

7. Oxidative stress Oxidative stress is an imbalance between free radicals and antioxidants in your body . Free radicals are oxygen-containing molecules with an uneven number of electrons. The uneven number allows them to easily react with other molecules . Free radicals can cause large chain chemical reactions in your body because they react so easily with other molecules. These reactions are called oxidation. They can be beneficial or harmful.

8. Harmfull effects on biomolecules Proteins:cause oxidation of sulfhydryl groups,and modification of AA. ROS may damage protein by fragmentation , aggregation results in the loss of biological activity of proteins Lipids: the polyunsaturated lipid molecule of cell membranes are particularly susceptible to damage free radicals process and contribute to the uncontrolled chain reaction Carbohydrates: glycation increase the susceptibility of proteins to the attack by free radicals

9. Harmfull effects on body Cardiovascular diseases: ox-LDL, formed by the action of free radicals , promote CHD and a therosclerosis Cancer: damage DNA and cause mutation and cytotoxicity ,play a key role in carcinogenesis Inflammatory diseases: damage on the extracellular componenets such as collagen and hyaluronic acid , promote glomerulonephritis and ulcerative colitis Respiratory diseases :destroy endothelium and cause lung edema. Cigarette smoke promote production of free radicals

10. Diabetes mellitus: destruction of islets results in pathogenesis Cataract Male infertility Aging process Others: parkingsons disease, alzheimers disease, multiple sclerosis,liver cirrhosis,muscular dystrophy Harmfull effects on body

11. Role of malondialdehyde in pathogenesis of diabetes ROS degrade polyunsaturated lipids, forming malondialdehyde . This compound is very reactive and toxic in nature and it causes toxic stress in cells and form covalent protein adducts which referred to as “advanced lipoprotein end product” and “advanced glycation end products” Malondialdehyde reacts with deoxyadenosine and deoxyguanosine in DNA forming DNA adducts primarly MIG which is a mutagenic Malondialdehyde modification of basic amino acid side chains also results in change in properties , for eg , in the charge profile of the molecules resulting in modified cell matrix interactions

12. Reference ESSENTIALS OF MEDICAL PHARMACOLOGY BY K.D TRIPATHI THE PHARMACOLOGICAL BASIS OF THERAPEUTICS , GOODMAN & GILMAN healthline.com/health/ oxidativestress