Mitigation of lead-induced neurotoxicity by the naringin: erythrocytes as neurons substitute markers.
This study aimed to investigate the effect of lead (Pb) on neuronal nitric oxide synthase (nNOS) activity using erythrocytes as neurons surrogate markers. Moreover, the protective effect of naringin (NAR) against lead acetate (PbAc)-induced neurotoxicity was investigated. Human erythrocytes were incubated with L-arginine (L-Arg), Nω-nitro-L-Arginine methyl ester ( L-NAME), NAR, PbAc, PbAc+L-Arg, PbAc+NAR, or PbAc+L-Arg+NAR. The present results revealed that incubation of erythrocytes with PbAc inhibited NOS activity and decreased nitrite levels as an index for nitric oxide (NO) production to values similar that of L-NAME as known NOS inhibitor. Likewise, PbAc induced a significant decrease in activities of ATPases and acetylcholinesterase compared to control cells. Furthermore, PbAc exposure significantly increased protein carbonyl content (PCC) and malondialdehyde (MDA) levels while significantly decrease the levels of reduced glutathione (GSH). On the contrary, incubation of erythrocytes with PbAc in the presence of L-Arg+NAR synergistically ameliorated the investigated parameters compared to erythrocytes incubated with PbAc alone. These data suggest that NAR can restore NO bioavailability in a situation of Pb-induced cellular damage. This attributed to antioxidant activity and restoration NOS activity.
Department of Pharmaceutics, Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia, gamal.harisa@yahoo.com.
Gamaleldin I
GI
Harisa
D000110:Acetylcholinesterase / Q000378:metabolism; D001120:Arginine / Q000494:pharmacology*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism*; D044950:Flavanones / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D050050:Protein Carbonylation
D044950:Flavanones; D009573:Nitrites; D009942:Organometallic Compounds; D009569:Nitric Oxide; D008315:Malondialdehyde; D001120:Arginine; D000110:Acetylcholinesterase; C005274:naringin; C008261:lead acetate; D019331:NG-Nitroarginine Methyl Ester