Pulmonary protective efficacy of S-2[2-aminoethylamino] ethyl phenyl sulphide (DRDE-07) and its analogues against sulfur mustard induced toxicity in mice.

Autor: Soni AK; Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India., Bhaskar ASB; Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India., Pathak U; Synthetic Chemistry Division, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India., Nagar DP; Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India., Gupta AK; Process Technology Division, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India., Kannan GM; Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior, 474 002, India. Electronic address: gmkannan@drde.drdo.in.
Jazyk: angličtina
Zdroj: Environmental toxicology and pharmacology [Environ Toxicol Pharmacol] 2020 May; Vol. 76, pp. 103333. Date of Electronic Publication: 2020 Feb 08.
DOI: 10.1016/j.etap.2020.103333
Abstrakt: Our previous study showed that percutaneous sulfur mustard (SM) exposure induced pulmonary toxicity, which was attenuated by DRDE-07 (S-2[2-aminoethylamino] ethyl phenyl sulphide) pretreatment. The present study aimed to evaluate the protective efficacy of DRDE-07 and its analogues viz., DRDE-30 (S-2(2-aminoethyl amino)ethyl propyl sulphide) and DRDE-35 (S-2(2-aminoethyl amino)ethyl butyl sulphide) against SM. Thirty minutes before percutaneous SM (0.8 LD 50 ) exposure, female Swiss mice were orally gavaged with DRDE-07 and its analogues(0.2 LD 50 ). Animals were sacrificed on day 3 and 7, BAL fluid (BALF) and lung tissue were collected for biochemical, histopathological studies. As results, DRDE-07 and its analogues were beneficial in reducing the number of BALF inflammatory cells, protein level, lactate dehydrogenase (LDH) activity, myeloperoxidase (MPO) and β-glucuronidase activity, while content of BALF and lung reduced glutathione level (GSH) were significantly protected. The pretreatment of DRDE-07 and its analogues inhibited the recruitment of inflammatory cells into the lung. The beneficial effects of DRDE-07 and its analogues were attributed to their antioxidant and anti-inflammatory activity. Among the analogues, DRDE-30 exhibited significant beneficial effects as compared to the other two compounds. These analogues may be considered as prototype candidate molecules as there is no effective antidote for SM toxicity.
Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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