Acute nephrotoxicity of cisplatin: Molecular mechanisms

Abstract

The nephrotoxic drugs have been responsible for about 20% of AKI episodes in inpatients and outpatients. The cisplatin nephrotoxicity is a major limiting factors in 20% of patients who have received the drug, triggering injuries in renal tubular epithelial cells. Cisplatin toxicity is determined by the target tissue and cells accumulation besides the interaction with various subcellular structures and macromolecules. Cisplatin accumulates and interferes with the functioning of different organelles such as mitochondria, lysosomes, endoplasmic reticulum, nuclei and cell membranes, causing inflammation and cell death. This review aims to define the pathophysiology and biochemistry of the cisplatin nephrotoxicity, reviewing the main molecular mechanisms that lead to tubular cisplatin toxicity.

Synergistic protective effect of <em>N</em>-acetylcysteine and taurine against cisplatin-induced nephrotoxicity in rats

“…The exact mechanism for this nephrotoxicity is not well defined, although several studies have been carried out in this regard. Previous studies have established that the generation of free radicals and induction of oxidative stress are strongly implicated in the nephrotoxicity of CDDP 28. The use of an antioxidant therapy may be effective in preventing or at least reducing the deleterious side effects of CDDP.…”

Loss of α(E)-catenin promotes Fas mediated apoptosis in tubular epithelial cells

“…Clinical studies performed in Spain showed the incidence of AKI is 3.5 times higher in aged patients (≥70 years) compared with those less than 70 years old [4]. In addition, increased medication use in elderly patients can also increase the incidence of AKI since nephrotoxic drugs are the cause for approximately 20% of AKI cases [5]. In our study, cisplatin, a widely used nephrotoxicant-induced AKI model, was used to investigate the pathophysiological mechanism of AKI in aged kidney [6].…”

“…The intrinsic and extrinsic pathways are two major caspase-dependent pathways to induce apoptosis, which are distinguished by the initiating signal [5]. The intrinsic pathway is triggered by cell stress-induced mitochondria outer membrane permeabilization (MOMP), resulting in the release of cytochrome c that activates caspase-9.…”

Cytotoxic effect ofErythroxylum daphnitesextract is associated with G1cell cycle arrest and apoptosis in oral squamous cell carcinoma

“…Most chemotherapy drugs target rapidly dividing cells, including healthy cells undergoing mitosis as well as cancer cells. 26,27 Therefore, the identification of new agents with a higher selectivity for cancer cells is crucial. Similar results were observed in a study by Horri et al, 28 who found that Rhinacanthus nasutus extract was strongly selective for an OSCC cell line when compared to gingival fibroblasts, pulp cells, and cells of the periodontal ligament.…”