Cisplatin Induces Kidney Cell Death via ROS-dependent MAPK Signaling Pathways by Targeting Peroxiredoxin I and II in African Green Monkey (Chlorocebus aethiops sabaeus) Kidney Cells.

BACKGROUND/AIM: Cisplatin [cis-diamminedichloroplatinum(II), CDDP] is a widely used and effective antitumor drug in clinical settings, notorious for its nephrotoxic side effects. This study investigated the mechanisms of CDDP-induced damage in African green monkey kidney (Vero) cells, with a focus on the role of Peroxiredoxin I (Prx I) and Peroxiredoxin II (Prx II) of the peroxiredoxin (Prx) family, which scavenge reactive oxygen species (ROS). MATERIALS AND METHODS: We utilized the Vero cell line derived from African green monkey kidneys and exposed these cells to various concentrations of CDDP. Cell viability, apoptosis, ROS levels, and mitochondrial membrane potential were assessed. RESULTS: CDDP significantly compromised Vero cell viability by elevating both cellular and mitochondrial ROS, which led to increased apoptosis. Pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) effectively reduced CDDP-induced ROS accumulation and subsequent cell apoptosis. Furthermore, CDDP reduced Prx I and Prx II levels in a dose- and time-dependent manner. The inhibition of Prx I and II exacerbated cell death, implicating their role in CDDP-induced accumulation of cellular ROS. Additionally, CDDP enhanced the phosphorylation of MAPKs (p38, ERK, and JNK) without affecting AKT. The inhibition of these pathways significantly attenuated CDDP-induced apoptosis. CONCLUSION: The study highlights the involvement of Prx proteins in CDDP-induced nephrotoxicity and emphasizes the central role of ROS in cell death mediation. These insights offer promising avenues for developing clinical interventions to mitigate the nephrotoxic effects of CDDP.

Minimizing patients total clinical condition deterioration in operating theatre departments.

The operating theatre is the most crucial and costly department in a hospital due to its expensive resources and high patient admission rate. Efficiently allocating operating theatre resources to patients provides hospital management with better utilization and patient flow. In this paper, we tackle both tactical and operational planning over short-term to medium-term horizons. The main goal is to determine an allocation of blocks of time on each day to surgical specialties while also assigning each patient a day and an operating room for surgery. To create a balance between improving patients welfare and satisfying the expectations of hospital administrators, we propose six novel deterioration rates to evaluate patients total clinical condition deterioration. Each deterioration rate is defined as a function of the clinical priorities of patients, their waiting times, and their due dates. To optimize the objective functions, we present mixed integer programming (MIP) models and two dynamic programming based heuristics. Computational experiments have been conducted on a novel well-designed and carefully chosen benchmark dataset, which simulates realistic-sized instances. The results demonstrate the capability of the MIP models in finding excellent solutions (maximum average gap of 4.71% across all instances and objective functions), though, requiring large run-times. The heuristic algorithms provide a time-efficient alternative, where high quality solutions can be found in under a minute. We also analyse each objective function's ability in generating high quality solutions from different perspectives such as patients waiting times, the number of scheduled patients, and operating rooms utilization rates. We provide managerial insights to the decision makers in cases where their intention is to meet KPIs and/or maintaining trade-offs between patients and administrators expectations, more fair assignments, or ensuring that the most urgent patients are taken care of first.