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. 2022 Apr 6;14(4):e23871.
doi: 10.7759/cureus.23871. eCollection 2022 Apr.

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study

Tülay Becerir  1 , Onur Tokgün  2 , Kubilay İnci  3 , İlknur Girişgen  4 , Selcuk Yuksel  5
Affiliations

Therapeutic Effect of Teneligliptin in Drug-Induced Nephrotoxicity: An In-Vitro Study

Tülay Becerir et al. Cureus. .

Abstract

Background Drug-induced nephrotoxicity is an important side effect of many commonly used drugs. In this study, we planned to evaluate the effects of teneligliptin (TG), which is a dipeptidyl peptidase-4 (DPP-4) inhibitor, on cell healing by creating nephrotoxicity models in human renal proximal tubule cell and human embryonic kidney epithelial cells cell lines in-vitro with cisplatin, vancomycin, and gentamicin. Methodology First, we determined the 50% inhibitory concentration doses of nephrotoxic drugs and the nephroprotective dose of TG. Then, we analyzed the difference in cell viability, apoptosis, and oxidative stress (reactive oxygen and nitrogen species (ROS/RNS) production) between TG-treated and untreated cells after nephrotoxicity occurred. Moreover, we evaluated the expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in cells. Results We found that when cell lines were treated after toxicity was induced with TG, cell viability increased, apoptosis and ROS/RNS production were significantly decreased, and expressions of KIM-1 and NGAL were significantly reduced. Conclusions This study showed that TG has positive effects on the recovery of drug-induced nephrotoxicity in an in-vitro setting.

Keywords: cisplatin; drug-induced nephrotoxicity; gentamicin; teneligliptin; vancomycin.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The effects of cisplatin, vancomycin, and gentamicin on cellular toxicity in HEK293T and HK-2 cell lines. IC50 doses of nephrotoxic drugs (cisplatin, vancomycin, and gentamicin).
IC50: 50% inhibitory concentration
Figure 2
Figure 2. Cell viability measurements in the evaluation of the therapeutic effect of teneligliptin in HK-2 (A) and HEK293T (B) cell lines. Teneligliptin significantly increases cell viability after the development of drug-induced nephrotoxicity in HK-2 and HEK293T cell lines.
*P < 0.05; Cis: cisplatin; Van: vancomycin; Gen: gentamicin; IC50: 50% inhibitory concentration
Figure 3
Figure 3. Analysis results of the antiapoptotic effect of teneligliptin in HK-2 (A) and HEK293T (B) cell lines. After the development of nephrotoxicity, teneligliptin treatment reduces the number of apoptotic cells.
**P < 0.01; ***P < 0.001; ****P < 0.0001; Cis: cisplatin; Van: vancomycin; Gen: gentamicin; TG: teneligliptin; IC50: 50% inhibitory concentration
Figure 4
Figure 4. In HK-2 (A) and HEK293T (B) cell lines. Results of reactive oxygen and nitrogen species (ROS and RNS) analysis. ROS and RNS production were higher in cells that were not treated with teneligliptin when compared with those treated with teneligliptin after the development of nephrotoxicity.
**P < 0.01; ***P < 0.001; ****P < 0.0001; Cis: cisplatin; Van: vancomycin; Gen: gentamicin; TG: teneligliptin
Figure 5
Figure 5. Results of analysis of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) in HEK293T (A) and HK-2 (B) cell lines. KIM-1 and NGAL expressions increased in cell lines with cisplatin, vancomycin, and gentamicin treatment. A reduction in the expression of these biomarkers in cell lines was observed when treated with teneligliptin after exposure to nephrotoxic agents.
*P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; Cis: cisplatin; Van: vancomycin; Gen: gentamicin; TG: teneligliptin
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References

    1. Drug-induced nephrotoxicity: pathogenic mechanisms, biomarkers and prevention strategies. Wu H, Huang J. Curr Drug Metab. 2018;19:559–567. - PubMed
    1. Drug-induced acute kidney injury: diverse mechanisms of tubular injury. Perazella MA. Curr Opin Crit Care. 2019;25:550–557. - PubMed
    1. The unique pharmacological and pharmacokinetic profile of teneligliptin: implications for clinical practice. Ceriello A, De Nigris V, Iijima H, Matsui T, Gouda M. Drugs. 2019;79:733–750. - PMC - PubMed
    1. Effect of switching to teneligliptin from other dipeptidyl peptidase-4 inhibitors on glucose control and renoprotection in type 2 diabetes patients with diabetic kidney disease. Kitada M, Ogura Y, Nitta K, et al. J Diabetes Investig. 2019;10:706–713. - PMC - PubMed
    1. Dipeptidyl peptidase-4 inhibitor teneligliptin accelerates recovery from cisplatin-induced acute kidney injury by attenuating inflammation and promoting tubular regeneration. Iwakura T, Zhao Z, Marschner JA, Devarapu SK, Yasuda H, Anders HJ. Nephrol Dial Transplant. 2019;34:1669–1680. - PubMed

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