Novel sila-amide derivatives of N-acetylcysteine protects platelets from oxidative stress-induced apoptosis.
Oxidative stress-induced platelet apoptosis is one among the many causes for the development and progression of many disorders like cardiovascular diseases, arthritis, Alzheimer's disease and many chronic inflammatory responses. Many studies have demonstrated the less optimal effect of N-acetyl cysteine (NAC) in oxidative stress-induced cellular damage. This could be due to its less lipophilicity which makes it difficult to enter the cellular membrane. Therefore in the present study, lipophilic sila-amide derivatives (6a and 6b) synthesized through the reaction of NAC with 3-Aminopropyltrimethylsilane and aminomethyltrimethylsilane were used to determine their protective property against oxidative stress-induced platelet apoptosis. At a concentration of 10 µM, compound 6a and 6b were able to significantly inhibit Rotenone/H2O2induced platelet apoptotic markers like reactive oxygen species, intracellular calcium level, mitochondrial membrane potential, cytochrome c release from mitochondrial to the cytosol, caspase-9 and -3 activity and phosphatidylserine externalization. Therefore, the compounds can be extrapolated as therapeutic agents to protect platelets from oxidative stress-induced platelet apoptosis and its associated complications.
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India.
Manoj
M
Paul
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India.
Ram M
RM
Thushara
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India.
Swamy
S
Jagadish
Organosilicon Research Center, University of Wisconsin, Madison, WI, 53706-1396, USA.
Uzma I
UI
Zakai
Organosilicon Research Center, University of Wisconsin, Madison, WI, 53706-1396, USA.
Robert
R
West
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India. kemparajuom@gmail.com.
Kempaiah
K
Kemparaju
Department of Studies in Biochemistry, University of Mysore, Manasagangothri, Mysore, 570 006, India. ksgbaboo@gmail.com.|Department of Studies and Research in Biochemistry, Tumkur University, Tumkur, 572 103, India. ksgbaboo@gmail.com.
Kesturu S
KS
Girish
D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology*; D000577:Amides; D017209:Apoptosis; D001792:Blood Platelets / Q000187:drug effects*; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018384:Oxidative Stress; D020011:Protective Agents / Q000737:chemistry; D012821:Silanes / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D020011:Protective Agents; D012821:Silanes; D000111:Acetylcysteine
N-Acetylcysteine; N-Acetylcysteine amide; Oxidative stress; Platelet apoptosis; Platelets; Reactive oxygen species