Comparative Pulmonary Protective Efficacy of Amifostine and it’s Analogue S-2(2-aminoethylamino)ethyl Phenyl Sulfide (DRDE-07) against Sulphur Mustard Induced Oxidative Stress and Inflammation in Female Mice

Prophylactic Treatment for Sulphur Mustard Poisoning

  • Alok Kumar Soni Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, INDIA.
  • Uma Pathak Division of Synthetic Chemistry, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, INDIA.
  • Durga Prasad Nagar Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, INDIA.
  • Arvind Kumar Gupta Process Technology Development Division, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, INDIA.
  • Gurusamy Mathu Kannan Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, Madhya Pradesh, INDIA.
Keywords: Amifostine, BALF, Chemical Warfare Agents, DRDE-07, Pulmonary injury, Oxidative stress, Sulfur mustard

Abstract

Aim: The present study was undertaken to investigate the comparative pulmonary protective efficacy of Amifostine (S-2[3-aminoprophylamino] ethyl phosphorothioate) and its analogues DRDE-07 (S-2(2-aminoethylamino) ethyl phenyl sulfide) against sulfur mustard toxicity in mice. Materials and Methods: Twenty female mice were divided into four groups: Control, SM group animals were percutaneously exposed to 16.2 mg/kg. The third and fourth group of animals received amifostine and DRDE-07 (210 and 250 mg/kg  respectively) through the oral route, 30 min before SM exposure. The clinical symptoms and body weight changes were observed daily and sacrificed on 7th day. Bronchoalveolar lavage fluid (BALF) and lung tissue
were collected for biochemical and histopathological studies. The following biochemical endpoints were studied in BALF (total cell count, lactate dehydrogenase, protein content, β-glucuronidase activity, MMP-2, 9 activity
and FSH) whereas reactive oxygen species (ROS), reduced glutathione (GSH), lipid peroxidation, superoxide dismutase, catalase and myeloperoxidase activity was measured in lung tissue. The above biochemical observations are also supported by histopathology studies. Results: Dermal exposure to SM significantly reduced body weight. The significant increase in BALF LDH leakage, protein content, cell number and MMPs activity in the SM exposed animals suggest disruption of endothelial barrier in the lung (p<0.05). Significant ROS generation (p<0.05) was observed in lung tissue of SM group which results in a significant decrease in SOD GSH
and CAT and an increase in MDA (p<0.05). These alterations in BALF as well in lung tissue due to SM exposure was significantly prevented by the pretreatment of amifostine and DRDE-07 (p<0.05). The histopathological observations also support the above results. The above results indicate that the preventive efficacy of DRDE-07 is better than amifostine. Conclusion: The percutaneous SM exposure-induced pulmonary damages were significantly protected by DRDE-07 than amifostine in mice.

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Figure 1: Experimental protocol.
Published
2020-03-12
How to Cite
1.
Soni A, Pathak U, Nagar D, Gupta A, Kannan G. Comparative Pulmonary Protective Efficacy of Amifostine and it’s Analogue S-2(2-aminoethylamino)ethyl Phenyl Sulfide (DRDE-07) against Sulphur Mustard Induced Oxidative Stress and Inflammation in Female Mice. ijpi [Internet]. 12Mar.2020 [cited 3Apr.2020];10(1):37-2. Available from: http://www.jpionline.org/index.php/ijpi/article/view/434