Document Type

Thesis

Date of Award

12-2021

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

MS in Environmental Toxicology

Committee Chairperson

Zivar Yousefipour

Committee Member 1

Shodimu-Emmanuel Olufemi

Committee Member 2

Rasoul Saneifard

Committee Member 3

Kasturi Ranganna

Keywords

Acrolein Amelioration, Compound-20 (Analog of Curcumin), Curcumin, Inflammation, Oxidative stress

Abstract

Research has shown that acrolein, a known environmental pollutant, contributes to generation of free radicals leading to oxidative stress and physiological damage. Curcumin has been known to improve damages from oxidative stress due to its antioxidative and anti-inflammatory properties. It has been reported that to exert such an effect, a large dose of curcumin needs to be consumed on daily bases due to its high excretion through kidney. Here in collaboration with Dr. Chelliah from department of pharmaceutical, an analog form of curcumin (compound-20) was synthesized with promising more potent activity and absorption. The objective of this study was to investigate if compound-20 could prevent acrolein induced oxidative stress in rats. Acrolein is a reactive aldehyde, which is released as a byproduct of organic combustion such as in cigarette smoke, burning of wood, automobile exhaust, diesel fuel, paraffin wax, and heating cooking oil at high temperatures. (Tanel et al., 2014; Stevens et al., 2008). Acrolein has its uses which include production of pesticides, algaecide, and aquatic herbicide in irrigation canals (Arntz et al., 2013). High level of acrolein has been reported in different disease conditions such as spinal cord injury, multiple sclerosis, diabetes mellitus, neurological, nephrological and hepatological toxicity, Alzheimer’s, and cardiovascular disease (Akshata et al., 2015). Curcumin is a natural product, widely used in cooking preparations thorough out the world. As a polyphenol compound, curcumin (CUR) is isolated from the rhizome of Curcuma longa and chemically defined as diferuloylmethane. CUR has powerful antioxidant and anti-inflammatory activities (Kunnumakkara et al., 2017). However, when consumed as a spice in preparation of food, large amount of the compound will be excreted due to its poor absorption from small intestine as well high metabolism by liver (Dei Cas and Ghidoni, 2019). To overcome these limitations, different approaches including synthesizing novel solid or liquid forms have investigated Here at Texas Southern University, our collaborator, Dr. Chelliah and his group have been successful in synthesizing several solid analogs of curcumin with more potent and absorption property (Chelliah et al., 2019). In this study, we hypothesized that one of the curcumins analog, which is referred as compound-20 here on, is effective on prevention/reversal of toxic damage caused by acrolein by improving antioxidant system, removing free radicals and ultimately, reducing the inflammation. Effects of compound-20 in amelioration of changes caused by acrolein was examined in rat’s serum. Lipid peroxidation, total glutathione, superoxide dismutase, and glutathione-s-transferase activities were measured using ELISA kits from ABCAM including Lipid peroxidation assay kit (Colorimetric), GSH + GSSG/GSH assay kit (Colorimetric), Superoxide dismutase activity (colorimetric), and GST activity assay kit (colorimetric) respectively.Male Sprague Dawley rats weighing 250-350kg were purchased from Envigo (Indianapolis 190 United States) and were divided into three groups: Control group (same amount of vehicle), acrolein group (2mg/kg/day, i.p 7days), and Group 3 includes rats treated with compound-20 (10mg/kg/day, 3days, gavage) before acrolein treatment of (2mg/kg/day, 4days i.p). At the end of the treatment, rats were sacrificed, and tissues and blood were harvested for further analysis. Blood was collected in heparin containing syringes (cardiopuncture, 8-10 ml) in anesthetized rats. Collected blood was centrifuged at 1000 X g for 10 minutes and the supernatant was collected. We used the serum to carry out different assays following manufacturer protocols. The results were analyzed using Unpaired t-test and one-way ANOVA and the data with P values P≤0.05 were reported as significant change. Our result showed a decreased level of GST activity, Glutathione, and SOD activity, but increased lipid peroxidation, in the group treated with acrolein. Addition of compound-20 (C20) increased glutathione, GST, AND SOD activities, while lipid peroxidation was decreased. In conclusion, based on our results, we are reporting that changes in rats after exposure to acrolein are ameliorated after addition of C20. Furthermore, we are including that daily dose of C20 might be a preventive approach to reduce effects of compounds like acrolein in population that are living in areas with high level of acrolein in the environment.

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