Toxicology International (Formerly Indian Journal of Toxicology)

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


Affiliations
1 Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India
2 Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, India
     

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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.

Keywords

Industrial Chemicals, Alpha-Ketoglutaric Acid, Sub-Micronic Aerosols, Inhalation Toxicity, BAL Fluid Analysis.
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  • Sub-Acute Inhalation Toxicity Study of Submicronic Alpha-Ketoglutarate Respiratory Formulation

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Authors

Rashid Ali
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India
Shaheen Sultana
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India
Sarwat Sultana
Department of Medical Elementology and Toxicology, Jamia Hamdard, New Delhi, India
Amit Kumar
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India
Aseem Bhatnagar
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India
Gaurav Mittal
Department of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defence R&D Organization, Delhi, India

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.

Keywords


Industrial Chemicals, Alpha-Ketoglutaric Acid, Sub-Micronic Aerosols, Inhalation Toxicity, BAL Fluid Analysis.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi2%2F146687