Keywords

Cisplatin, Pyroptosis, NLRP3 Inflammasome, Skeletal muscle dysfunction, Caspase 1, Atrophy

Abstract

Cisplatin, a platinum-based drug extensively utilized in chemotherapy, is effective in treating a variety of cancer forms. Clinical studies have shown that cisplatin triggers muscle wasting and dysfunction, which significantly impacts the clinical prognosis of cancer patients. Additionally, recent research revealed that pyroptosis, a highly inflammatory cell-death, mediates muscle wasting. However, its role in cisplatin-induced skeletal muscle toxicity remains unclear. Therefore, we hypothesized that cisplatin induces myotoxicity and causes adverse skeletal muscle remodeling through pyroptosis. In this study, C57BL/6 mice (10±2 weeks old) were divided into two groups: Control(saline) and Cisplatin (cisplatin). Saline and Cisplatin were respectively administered via intraperitoneal injection (i.p.) at 2.3mg/kg body weight (BW) for 5 consecutive days (first cycle), followed by 5 days of rest, and then another 5 consecutive days (second cycle), making it a total of 10 injections and a cumulative dose of 23 mg/kg BW. At day 29 (D29), the muscle function was assessed by subjecting the mice to grip force tests and weight tests. Gastrocnemius muscle tissues from sacrificed mice were collected for histological analysis. Further analysis for protein expression of pyroptosis-associated markers (TLR4, NLRP3, Caspase-1, IL-1β, IL-18, and GSDMD) was performed using immunohistochemistry and western blotting. The stimulation of TLR4 leads to the formation of the NLRP3 inflammasome which initiates the activation of Caspase-1, Il-1β and IL-18, along with the executioner of pyroptosis, GSDMD. Our data revealed that cisplatin-treatment significantly (P

Completion Date

2024

Semester

Summer

Committee Chair

Singla, Dinender

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biotechnology

Format

application/pdf

Identifier

DP0028560

URL

https://purls.library.ucf.edu/go/DP0028560

Language

English

Release Date

8-15-2029

Length of Campus-only Access

5 years

Access Status

Masters Thesis (Campus-only Access)

Campus Location

Orlando (Main) Campus

Accessibility Status

Meets minimum standards for ETDs/HUTs

Download

Restricted to the UCF community until 8-15-2029; it will then be open access.

Share

COinS