D-Limonene Alleviates Acute Kidney Injury Following Gentamicin Administration in Rats: Role of NF-κB Pathway, Mitochondrial Apoptosis, Oxidative Stress, and PCNA

Author:

Babaeenezhad Esmaeel1ORCID,Hadipour Moradi Forouzan2,Rahimi Monfared Sobhan23,Fattahi Mohammad Davood1,Nasri Maryam23ORCID,Amini Abdolhakim23,Dezfoulian Omid4ORCID,Ahmadvand Hassan23ORCID

Affiliation:

1. Department of Clinical Biochemistry, School of Medicine, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2. Razi Herbal Medicines Research Center, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

3. Department of Clinical Biochemistry, Faculty of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran

4. Department of Pathobiology, School of Veterinary Medicine, Lorestan University, P.O. Box 465, Khorramabad, Iran

Abstract

Clinical application of gentamicin (GM) is well known to be associated with the development of acute kidney injury (AKI). This study was the first to investigate the possible protective effects of D-limonene (D-lim) on AKI following GM administration in rats. 32 rats arranged in four groups ( n = 8 ): (1) the control group received saline intraperitoneally (0.5 ml/day) and orally (0.5 ml/day), (2) the D-lim group received D-lim (100 mg/kg) orally and saline (0.5 ml/day) intraperitoneally, (3) the GM group received GM (100 mg/kg/day) intraperitoneally and saline (0.5 ml/day) orally, and (4) the treated group received intraperitoneal GM (100 mg/kg) and oral D-lim (100 mg/kg). All treatments were performed daily for 12 consecutive days. Results revealed that D-lim ameliorated GM-induced AKI, oxidative stress, mitochondrial apoptosis, and inflammation. D-lim showed nephroprotective effects as reflected by the decrease in serum urea and creatinine and improvement of renal histopathological changes. D-lim alleviated GM-induced oxidative stress by increasing the activities of renal catalase, serum and renal glutathione peroxidase, and renal superoxide dismutase and decreasing renal malondialdehyde and serum nitric oxide levels. Intriguingly, D-lim suppressed mitochondrial apoptosis by considerably downregulating Bax and caspase-3 (Casp-3) mRNA and protein expressions and markedly enhancing Bcl2 mRNA and protein expressions. Furthermore, D-lim significantly decreases GM-induced inflammatory response through downregulation of NF-κB, IL-6, and TNF-α mRNA and/or protein expressions and decrease in renal myeloperoxidase activity. Finally, D-lim remarkably downregulated PCNA protein expression in the treated group compared with the GM group. In brief, this study showed that D-lim alleviated AKI following GM administration in rats, partially through its antioxidant, anti-inflammatory, and antiapoptotic activities as well as downregulation of PCNA expression.

Funder

Lorestan Medical University

Publisher

Hindawi Limited

Subject

Cell Biology,Ageing,General Medicine,Biochemistry

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