Document Type

Dissertation

Date of Award

10-2025

School/College

College of Science, Engineering, and Technology (COSET)

Degree Name

Ph.D. in Environmental Toxicology

Committee Chairperson

Zivar Yousefipour

Committee Member 1

Bobby Wilson

Committee Member 2

Qiao Fengxiang

Committee Member 3

Rasoul Saneifard

Keywords

acrolein-induced, Beclin-1, Compound-20

Abstract

Study aim is to determine the role of p38-MAPK/Nrf2 and NF-κB signaling in acrolein-induced kidney injury. Evaluate autophagy modulation and whether curcumin and Compound 20 mitigate acrolein-induced kidney injury by modulating p38-MAPK/Nrf2 and NF-κB pathways. Male Sprague–Dawley rats were randomly divided into groups (n = 5) for control and treatment. All rats were fasted for 4–5 hours daily throughout the 10-day study period. Male Sprague–Dawley rats were administered peanut butter, curcumin, or Compound-20 mixed with peanut butter via voluntary oral consumption, followed by intraperitoneal (IP) administration of acrolein. The animals were randomly divided into groups (n = 5) for control and treatment. All rats were fasted for 4–5 hours daily throughout the 10-day study period. The control group received peanut butter only. The treatment groups were administered acrolein at a dose of 2 mg/kg/day via IP injection, while other groups received the following treatments: Curcumin (100 mg/kg/day), Compound-20 (10 mg/kg/day), Acrolein (2 mg/kg/day) + Curcumin (100 mg/kg/day), and Acrolein (2 mg/kg/day) + Compound-20 (10 mg/kg/day). Serum creatinine, albumin, triglyceride and kidney tissue glutathione (GSH), superoxide dismutase (SOD), levels were measured using ELISA kits (Abcam and Bioassay). Data were analyzed using unpaired t-tests and one-way ANOVA, with p ≤ 0.05 considered statistically significant. The experimental findings demonstrated that treatment with curcumin and Compound-20 reversed the nephrotoxic effects of acrolein by activating the Nrf2–Keap1 signaling pathway, leading to upregulation of GST and SOD levels. Data suggest that activation of the p38 MAPK pathway by acrolein directly contributes to renal damage, as reflected by elevated creatinine and decreased albumin levels. However, both curcumin and Compound-20 mitigated this damage through their antioxidant and anti-inflammatory properties. Furthermore, the acrolein-induced decrease in Beclin-1 expression appeared to impair the protective autophagic response, resulting in cellular damage, heightened inflammation, and fibrosis. Curcumin and Compound-20 enhanced Beclin-1 function, offering a promising therapeutic strategy to attenuate severe renal injury and promote recovery following acrolein exposure.

Included in

Toxicology Commons

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