Table (1).

Overview of in vitro and in vivo models used to study the key factors in CDDP-induced nephrotoxicity. ‘PTs’, ‘PTCs’ and ‘CDDP’ denote proximal tubules, proximal tubular cells and Cisplatin, respectively.

Experimental Models	Approaches	Observations	References
In vitro models use to study CDDP-induced nephrotoxicity
Yeast	Deletion of Ctr1 transporter to track changes in CDDP uptake	Increased CDDP resistance and reduced intracellular accumulation	[41]
Mouse cell lines	Lack of Ctr1 alleles to study changes in CDDP uptake	Increased CDDP resistance and reduced intracellular accumulation	[41]
Human PTs from healthy kidneys	Cimetidine OCT2 inhibition to track changes in CDDP uptake	Decreased CDDP uptake	[43]
Human PTs from diabetic kidneys	Reduced OCT2 expression due to diabetic condition	Decreased CDDP uptake	[2, 43]
TNFR1-deficient cells	Ablation of TNFR1 gene	Increased resistance to CDDP-induced cell death	[53]
Fas-mutant cells	Effect of Fas gene ablation on the Fas-mediated apoptotic pathway	Increased resistance to CDDP-induced cell death	[53]
Rabbit PTCs	p53 inhibition	Decreased CDDP-induced apoptosis	[58, 68, 71]
In vivo models use to study CDDP-induced nephrotoxicity
TNFR1-deficient mice TNFR2-deficient mice	Ablation of TNFR1 or TNFR2 gene to study changes in CDDP pathogenesis	Amelioration of CDDP-induced renal failure	[53, 86]
TNF-α-deficient mice	Effect of TNF-α deficiency in the activation of cytokines due to CDDP	Resistance to CDDP-nephrotoxicity	[2, 52]
Fas-mutant mice	Ablation of Fas gene to reveal its involvement on CDDP-induced cell death	Diminished CDDP-induced cell death and renal dysfunction	[53]
Bax-deficient mice	Bax gene knocked out to determine the pathological role of Bax	Decreased apoptosis and tissue damage induced by CDDP	[50]
JNK inhibition rat model	Inhibition of JNK using SP600125	Reduction of the apoptotic cell death and inflammation due to CDDP	[88]
OCT1/OCT2-deficient mice	Role of OCTs in CDDP oto- and nephron-toxicity	Reduced CDDP toxicity	[43, 44]
nu/nu mice (T-cell deficient)	Possible protective effects of CD+4CD25+Treg cells	Attenuation of CDDP-induced renal dysfunction and tubular injury, and increased survival	[9]
CD4- or CD8-T-cell-deficient mice	Role for T-lymphocytes on CDDP-induced AKI	Attenuation of renal dysfunction after CDDP administration	[101]