Date of Award

2026

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Gary O. Rankin

Second Advisor

Dr. Monica Valentovic

Third Advisor

Dr. Michael Hambuchen

Fourth Advisor

Dr. Hasan Koc

Abstract

Brominated and chlorinated benzenes are common industrial chemicals linked to kidney injury. This study evaluated the nephrotoxicity of several mono- and dihalogenated derivatives using isolated kidney cells from male Fischer 344 rats. LDH release and trypan blue exclusion were measured after 30- and 60-minute exposures to 0.25–1.0 mM to test compounds. Toxicity increased with increased concentration and longer times. Mixed-halogen bromobenzenes, particularly 1-bromo-4-chlorobenzene, showed one of the highest toxicity levels, while 1,4dichlorobenzene was the most toxic chlorobenzene. Antioxidants (glutathione, ascorbate, and αtocopherol) markedly reduced injury, indicating oxidative mechanisms play a role in toxicity. cytochromes P450 (CYP) inhibitors (piperonyl butoxide and metyrapone) decreased toxicity, demonstrating that metabolic activation contributed to cell damage. Deferoxamine reduced injury by limiting iron-driven radical formation. These findings show that halogen substitution patterns strongly influence cytotoxicity and that oxidative stress and CYP-dependent metabolism drive the nephrotoxic response to dihalobenzene exposure.

Subject(s)

Pharmaceutical chemistry.

Pharmacology.

Kidneys.

Hazardous substances.

Toxicity testing -- In vitro.

Benzene.

Antioxidants.

Deferoxamine.

Oxidative stress.

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