The Authors Reply

Lázaro, Alberto; Humanes, Blanca; Jado, Juan Carlos; Tejedor, Alberto

doi:10.1038/ki.2013.42

Cited by 3 publications

(3 citation statements)

References 13 publications

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“…On the other hand, the influence of sex on cisplatin susceptibility in rodents is less conclusive. Some researchers reported that male Wistar rats have higher susceptibility to cisplatin nephrotoxicity than females [ 122 , 171 , 172 ], while others found no difference [ 36 , 54 , 124 , 168 ]. Interestingly, in ovariectomized Wistar rats estrogen showed no effects on cisplatin nephrotoxicity [ 173 ], while in castrated Wistar rats testosterone showed protective effects at low dose but harmful effects at high dose [ 174 ].…”

Section: Factors Modifying Cisplatin Nephrotoxicitymentioning

confidence: 99%

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Perše

Večerić-Haler

2018

BioMed Research International

170

140

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Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed. Given the complex pathogenesis of kidney injury, which involves both local events in the kidney and interconnected and interdependent systemic effects in the body, cisplatin rodent model is indispensable in the investigation of underlying mechanisms and potential treatment strategies of both acute and chronic kidney injury. Cisplatin rodent model is well appreciated and widely used model due to its simplicity. It has many similarities to human cisplatin nephrotoxicity, which are mentioned in the paper. In spite of its simplicity and wide applicability, there are also traps that need to be taken into account when using cisplatin model. The present paper is aimed at giving a concise insight into the complex characteristics of cisplatin rodent model and heterogeneity of cisplatin dosage regimens as well as outlining factors that can severely influence the outcome of the model and the study. Challenges for future research are also mentioned.

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Section: Factors Modifying Cisplatin Nephrotoxicitymentioning

confidence: 99%

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges

Perše

Večerić-Haler

2018

BioMed Research International

170

140

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“…Cisplatin is one of the most potent antineoplastics used in the treatment of various types of cancer; however, approximately one-third of patients undergoing cisplatin treatment experience acute kidney injury, with decreased glomerular filtration rate (GFR), increased serum creatinine and blood urea nitrogen (BUN), and electrolyte imbalance [1][2][3][4]. This cisplatin-induced nephrotoxicity limits the clinical use of the drug [1,4,5].…”

Section: Introductionmentioning

confidence: 99%

“…This cisplatin-induced nephrotoxicity limits the clinical use of the drug [1,4,5]. A wide body of experimental evidence indicates that cilastatin, a specific inhibitor of renal dehydropeptidase-I (DHP-I), can protect proximal tubular epithelial cells from the damage caused by cisplatin, without compromising the drug's therapeutic effect on cancer cells [1][2][3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats

González-Fernández

González-Nicolás

Morales

et al. 2022

Cells

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The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I.

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