title: Ameliorative potential of alpha-ketoglutaric acid (AKG) on acute lung injuries induced by ammonia inhalation in rats.
abstract: BACKGROUND
  Toxicants such as ammonia, if inhaled, can damage respiratory tract leading to acute lung injury and pulmonary edema. Besides being a possible threat for the workers in chemical industry, easy availability and the toxic nature of ammonia may be used by terror groups for inflicting mass casualty among vulnerable population. In the present study, we have evaluated the therapeutic efficacy of alpha-ketoglutarate (AKG) to mitigate acute effects of ammonia on lung structure and antioxidant status in experimental animals.
  
  
  METHODS
  Acute lung injury (ALI) models were developed by inhalation of aerosols of liquid ammonia in male Sprague Dawley rats. AKG (5%) respiratory fluid was inhaled by nebulization once daily for 5 days. Animals were euthanized and their blood samples were collected for hematology and serum biochemistry analysis. Total cell count, total protein (TP), lactate dehydrogenase (LDH), antioxidant enzyme activity (CAT, SOD, GSH), and malonaldialdehyde (MDA) formation were measured in bronchoalveolar lavage (BAL) fluid.
  
  
  RESULTS
  Treatment with AKG showed significant lung protection by lowering the levels of total cell count, TP, LDH, superoxide dismutase (SOD), and MDA in BAL fluid. There was a marked increase in catalase (CAT) and glutathione (GSH) content of BAL fluid post-AKG inhalation. Histopathology of lung tissue correlated with cellular and biochemical findings indicate therapeutic efficacy of AKG against ammonia-induced lung injuries.
  
  
  CONCLUSIONS
  The data suggest a possible therapeutic role of AKG inhalation against ammonia-induced structural and inflammatory changes in the lung.
authors.affiliation: Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Delhi, India.
authors.forename: Rashid
authors.initials: R
authors.lastname: Ali
authors.forename: Gaurav
authors.initials: G
authors.lastname: Mittal
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
authors.forename: Aseem
authors.initials: A
authors.lastname: Bhatnagar
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D000641:Ammonia / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000008:administration & dosage*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D007656:Ketoglutaric Acids / Q000008:administration & dosage*; D008168:Lung / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000931:Antidotes; D007656:Ketoglutaric Acids; D000641:Ammonia