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Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity.
J Pharm Pharmacol. 2016 Apr; 68(4):523-32.JP

Abstract

OBJECTIVE

This study aimed to investigate the potential protective effect of sitagliptin on gentamicin-induced nephrotoxicity and to elucidate the underlying mechanism.

METHODS

Wistar rats were allocated as follows: Gentamicin group: received gentamicin intraperitoneally (100 mg/kg/day); Gentamicin plus sitagliptin group: received simultaneous gentamicin and sitagliptin (30 mg/kg/day orally); Sitagliptin group: received only sitagliptin; and

CONTROL GROUP

received saline. Blood urea nitrogen (BUN), serum creatinine, urine protein levels and histopathology of kidney tissues were evaluated. The activity of mitochondrial enzyme complexes reflects the mitochondrial function. Oxidative stress biomarkers and immunohistochemical studies for apoptotic markers caspase-3 and bax were evaluated.

KEY FINDINGS

Gentamicin causes significant elevation of BUN, serum creatinine and urine proteins. Oxidative stress was revealed by decreased superoxide dismutase activity and catalase activity, glutathione depletion and increased malondialdehyde. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicates mitochondrial dysfunction, along with significant elevation in renal caspase-3 and bax. The aforementioned markers and the histological injury in renal tubules were significantly reversed upon sitagliptin treatment.

CONCLUSION

These findings suggest that sitagliptin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction and apoptosis in the kidney.

Authors+Show Affiliations

Faculty of Medicine, Pharmacology Department, Ain-Shams University, Cairo, Egypt.Faculty of Medicine, Pharmacology Department, Ain-Shams University, Cairo, Egypt.Faculty of Medicine, Histology Department, Ain-Shams University, Cairo, Egypt.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27019059

Citation

Abuelezz, Sally A., et al. "Alleviation of Renal Mitochondrial Dysfunction and Apoptosis Underlies the Protective Effect of Sitagliptin in Gentamicin-induced Nephrotoxicity." The Journal of Pharmacy and Pharmacology, vol. 68, no. 4, 2016, pp. 523-32.
Abuelezz SA, Hendawy N, Abdel Gawad S. Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity. J Pharm Pharmacol. 2016;68(4):523-32.
Abuelezz, S. A., Hendawy, N., & Abdel Gawad, S. (2016). Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity. The Journal of Pharmacy and Pharmacology, 68(4), 523-32. https://doi.org/10.1111/jphp.12534
Abuelezz SA, Hendawy N, Abdel Gawad S. Alleviation of Renal Mitochondrial Dysfunction and Apoptosis Underlies the Protective Effect of Sitagliptin in Gentamicin-induced Nephrotoxicity. J Pharm Pharmacol. 2016;68(4):523-32. PubMed PMID: 27019059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alleviation of renal mitochondrial dysfunction and apoptosis underlies the protective effect of sitagliptin in gentamicin-induced nephrotoxicity. AU - Abuelezz,Sally A, AU - Hendawy,Nevien, AU - Abdel Gawad,Sara, Y1 - 2016/03/28/ PY - 2015/10/20/received PY - 2016/01/30/accepted PY - 2016/3/29/entrez PY - 2016/3/29/pubmed PY - 2017/5/10/medline KW - apoptosis KW - gentamicin KW - mitochondrial dysfunction KW - nephrotoxicity KW - oxidative stress KW - sitagliptin SP - 523 EP - 32 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 68 IS - 4 N2 - OBJECTIVE: This study aimed to investigate the potential protective effect of sitagliptin on gentamicin-induced nephrotoxicity and to elucidate the underlying mechanism. METHODS: Wistar rats were allocated as follows: Gentamicin group: received gentamicin intraperitoneally (100 mg/kg/day); Gentamicin plus sitagliptin group: received simultaneous gentamicin and sitagliptin (30 mg/kg/day orally); Sitagliptin group: received only sitagliptin; and CONTROL GROUP: received saline. Blood urea nitrogen (BUN), serum creatinine, urine protein levels and histopathology of kidney tissues were evaluated. The activity of mitochondrial enzyme complexes reflects the mitochondrial function. Oxidative stress biomarkers and immunohistochemical studies for apoptotic markers caspase-3 and bax were evaluated. KEY FINDINGS: Gentamicin causes significant elevation of BUN, serum creatinine and urine proteins. Oxidative stress was revealed by decreased superoxide dismutase activity and catalase activity, glutathione depletion and increased malondialdehyde. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicates mitochondrial dysfunction, along with significant elevation in renal caspase-3 and bax. The aforementioned markers and the histological injury in renal tubules were significantly reversed upon sitagliptin treatment. CONCLUSION: These findings suggest that sitagliptin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction and apoptosis in the kidney. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/27019059/Alleviation_of_renal_mitochondrial_dysfunction_and_apoptosis_underlies_the_protective_effect_of_sitagliptin_in_gentamicin_induced_nephrotoxicity_ L2 - https://doi.org/10.1111/jphp.12534 DB - PRIME DP - Unbound Medicine ER -