Naringin regulates glutamate-nitric oxide cGMP pathway in ammonium chloride induced neurotoxicity.
Naringin, plant bioflavonoid extracted mainly from grapefruit and other related citrus species. This study was designed to assess the neuroprotective effect of naringin on ammonium chloride (NH4Cl) induced hyperammonemic rats. Experimental hyperammonemia was induced by intraperitonial injection (i.p) of NH4Cl (100mg/kg body weight (b.w.)) thrice a week for 8 consecutive weeks. Hyperammonemic rats were treated with naringin (80mg/kg b.w.) via oral gavage. Naringin administration drastically restored the levels of blood ammonia, plasma urea, nitric oxide (NO), glutamate, glutamine, lipid peroxidation, lipid profile, activities of liver marker enzymes, antioxidant status and sodium/potassium-ATPase (Na+/K+-ATPase). In addition, naringin supplementation reverted back the pathological changes of liver, brain and kidney tissues, the expressions of Glutamine synthetase (GS), Na+/K+-ATPase, neuronal nitric oxide (nNOS) and soluble guanylate cyclase (sGC) in hyperammonemic rats. Hence, this study suggested that nargingin exhibited their protective effect against NH4Cl induced toxicity via enhancing the activities of antioxidant enzymes and inhibiting the lipid peroxidation process. Take together, this study provides data that naingin effectively reduced neurotoxicity by attenuating hyperammonemia, suggesting that naringin act as a potential therapeutic agent to treat hyperammonemic rats.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, India.
Arumugam
A
Ramakrishnan
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, India. Electronic address: nvkbiochem@yahoo.co.in.
Natesan
N
Vijayakumar
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, India.
Mani
M
Renuka
D000641:Ammonia / Q000097:blood; D000643:Ammonium Chloride; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D044950:Flavanones / Q000494:pharmacology*; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000097:blood*; D022124:Hyperammonemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D009569:Nitric Oxide / Q000097:blood*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D015415:Biomarkers; D044950:Flavanones; D008055:Lipids; D018696:Neuroprotective Agents; D000643:Ammonium Chloride; D009569:Nitric Oxide; D018698:Glutamic Acid; D000641:Ammonia; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000071756:Soluble Guanylyl Cyclase; D005974:Glutamate-Ammonia Ligase; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP; C005273:naringenin
Antioxidant status; Genomic profile; Hyperammonemia; Lipid profile; Naringin