Drug Res (Stuttg) 2020; 70(01): 49-56
DOI: 10.1055/a-1017-5085
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

The Nephroprotective Role of Carnosine Against Ifosfamide-Induced Renal Injury and Electrolytes Imbalance is Mediated Via the Regulation of Mitochondrial Function and Alleviation of Oxidative Stress

Mohammad Mehdi Ommati
1  College of Life Sciences, Shanxi Agricultural University, Taigu, P. R. China
,
Omid Farshad
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Vahid Ghanbarinejad
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Hamid Reza Mohammadi
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4  Hepatitis Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
,
Mousavi Khadijeh
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Azarpira Negar
,
Mahboubi Zahra
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Farshid Ilkhaninasab
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
,
Leila Moezi
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5  Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
,
Reza Heidari
2  Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
› Institutsangaben
Acknowledgments This investigation was financially supported by the Vice Chancellor of Research Affairs of Shiraz University of Medical Sciences (Grant # 95–01–36–13619). Authors thank Pharmaceutical Sciences Research Center (PSRC) of Shiraz University of Medical Sciences for providing technical facilities to carry out this study.
Weitere Informationen

Publikationsverlauf

received 07. April 2019

accepted 19. September 2019

Publikationsdatum:
31. Oktober 2019 (online)

Abstract

Background Ifosfamide (IFO) is an alkylating agent administered against different types of malignancies. Several cases of renal injury and serum electrolytes disturbances have been reported in IFO-treated patients. Oxidative stress and mitochondrial dysfunction are suspected of being involved in the mechanism of IFO nephrotoxicity. Carnosine is a dipeptide which its antioxidant and mitochondria protecting properties have been mentioned in different experimental models. The current study aimed to evaluate the nephroprotective properties of carnosine against IFO-induced renal injury.

Methods Rats were treated with IFO (50 mg/kg, i.p) alone or in combination with carnosine. Serum and urine biomarkers of renal injury in addition to kidney markers of oxidative stress were evaluated. Moreover, kidney mitochondria were isolated, and some mitochondrial indices were assessed.

Results Elevated serum creatinine and BUN, hypokalemia, and hypophosphatemia, in addition, to an increase in urine glucose, protein, γ-GT, and alkaline phosphatase (ALP), were evident in IFO-treated animals. IFO also caused an increase in kidney reactive oxygen species (ROS) and lipid peroxidation (LPO). Renal GSH levels and antioxidant capacity were also depleted with IFO therapy. Mitochondrial dehydrogenase activity, GSH level, membrane potential, and ATP content were decreased while mitochondrial LPO and permeabilization were increased in IFO group. Carnosine (250 and 500 mg/kg, i.p) mitigated IFO-induced oxidative stress and mitochondrial impairment in renal tissue.

Conclusion Our data suggest mitochondrial dysfunction and oxidative stress as fundamental mechanisms of renal injury induced by IFO. On the other hand, carnosine supplementation protected kidneys against IFO-induced injury through regulating mitochondrial function and mitigating oxidative stress.

* The authors contributed equally to this work.