Hematotoxicity of Co-Administration of Bisphenol A and Acetaminophen in Rats and its Amelioration by Melatonin

Abstract

Background: Hematotoxicity is an underexplored end point of toxicity in most of the chemical exposures. An adverse effect on the hematological system arising out of xenobiotic exposure causes impaired hemostasis and coagulation leading to disease. BPA and acetaminophen are widely used synthetic chemicals the world over and both are known and have numerous toxic effects. Since both can be simultaneously exposed to humans over a period of time, we hypothesized that their exposure can cause hematotoxicity, which may be ameliorated by melatonin. Objective: In the current study, we aimed to find the effect of single and co-treatment of bisphenol A and acetaminophen on the RBC and coagulation factors in rats and amelioration of impairment by melatonin. Methods: Oxidative stress in red blood cells, bleeding time, blood clotting time, prothrombin time, and partial thromboplastin time, and fibrinogen levels were assessed as indicators of hematotoxicity. With treatment of bisphenol A and acetaminophen as single and co treatments and amelioration of the same by melatonin was evaluated. Results: An increase in RBC oxidative stress and decrease in bleeding time, blood clotting time, prothrombin time, and partial thromboplastin time along with an increase in fibrinogen levels was observed with bisphenol A and acetaminophen treatment, which was further aggravated with co-treatment of the two. Melatonin treatment, however, was seen to decrease the increase in oxidative stress and ameliorate the impairment in coagulation factors. Conclusion: Bisphenol A and acetaminophen cause an increase in oxidative stress in the red blood cells and cause a shift towards pro-coagulation, which is alleviated by treatment with melatonin.