Toxicological and behavioral study of two potential antibacterial agents:4-chloromercuribenzoic acid and quercetin on Swiss-albino mice

Abstract

Global dissemination of carbapenem resistant-Gram negative bacteria (CR-GNB) is supposed to be clinically alarming because it extremely delimits the treatment options against serious infections. 4-Chloromercuribenzoic acid (pCMB) is an efficient metallo-enzyme inhibitor, and quercetin is known for antioxidant, antiviral, anticancer, antimicrobial, and anti-inflammatory activities. These two compounds could be considered as potential candidates for the treatment of CR-GNB mediated infections. Hence, in this study, antibacterial activity of pCMB and quercetin was evaluated against CR-GNB through minimum inhibitory concentration (MIC) determination. Toxicity of pCMB and quercetin was evaluated by LC₅₀ calculation through brine shrimp test (BST) and by investigating hematological, serum biochemical, and histopathological parameters in Swiss-albino mice. Moreover, aggressive–depressive–cognitive behavioral effects of pCMB and quercetin on murine model were evaluated. All the carbapenem resistant isolates (CR-GNB) exhibited MIC values in the range of 4–256 μg/ml, 16–256 μg/ml, and 64–1024 μg/ml for pCMB, quercetin, and meropenem, respectively. BST determined LC₅₀ of pCMB and quercetin at 91.57 ± 0.35 mg/L and 448.45 ± 0.46 mg/L, respectively. Oral administration of low dose of pCMB and quercetin did not induce any significant changes in morphological, behavioral, hematological, serum biochemical, and histopathological parameters among Swiss-albino mice. But, a high dose of pCMB and quercetin exhibited slight toxicity. However, no death was reported for any dosage of pCMB and quercetin. Therefore, pCMB and quercetin might be considered for further investigations on alternative therapeutics to combat against CR-GNB.

Keywords:

• Minimum inhibitory concentration
• brine shrimp
• subacute toxicity
• hematological test
• behavioral test

Acknowledgments

Authors acknowledge kind help of Dr. B. K. Mahapatra, Principal Scientist & Officer-in-Charge, ICAR-Central Institute of Fisheries Education, Kolkata, India, for generously gifting Artemia salina cysts and providing facilities for their hatching. Authors also appreciate help provided by Mr. P. K. Behera, Senior Technical Assistant, ICAR-Central Institute of Fisheries Education, Kolkata, India, and Mr. Siddharta Sengupta, ICMR-Senior Research Fellow, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, India, for carrying out hatching experiment and recording data related to behavioral experiments, respectively.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

Authors gratefully acknowledge the financial support from Indian Council of Medical Research by sanctioning fellowship to Arijit Pal [no. 3/1/3/WL/JRF-2011/HRD-129 (41937)].