Sub-Acute Inhalation Toxicity Study of Submicronic Alpha-Ketoglutarate Respiratory Formulation

Abstract

Alpha Ketoglutaric Acid (AKG), one of two ketone derivatives of glutaric acid is an important biological compound that serves as a natural scavenger of ammonium ion, facilitating its conversion to amino acids and protein. AKG inhalation has potential therapeutic role against ammonia-induced structural and inflammatory changes in the lungs. In the present study sub-acute inhalation toxicity of a novel submicronic AKG respiratory formulation was evaluated in Sprague Dawley rats. Sub-acute inhalation toxicity study of novel AKG respiratory formulation at doses, 1, 3 and 5% was conducted as per Schedule-'Y' guidelines of ICMR, India. Hematological, serum biochemical and lung toxicity biomarkers in bronchoalveolar lavage (BAL) fluid were determined. Histopathological analysis of lung tissues and other vital organs was carried out to observe any microscopic changes. Hematology, serum biochemistry and lung toxicity biomarkers in BAL fluid revealed no adverse effects of AKG inhalation except for a slight increase in levels of BAL fluid protein. At autopsy, no histopathological changes in major vital organs, including the lungs were observed. The safety evaluation data suggest that aerosols of submicronic AKG respiratory formulation are safe for inhalation and could be developed as a potential therapeutic option against lung injuries induced through chemical toxicants such as ammonia.