Protective effect of tert-butylhydroquinone against cisplatin-induced hepatorenal injury via modulating oxidative stress, inflammation, and apoptosis

Abstract

Context

Cisplastin (CDDP) is a chemotherapeutic drug frequently used to manage a variety of cancers. However, its use is associated with hepatorenal toxicity resulting from elevated reactive oxygen species production.

Objective

Herein, the hepatorenal protective effect of tert-butylhydroquinone (tBHQ) in cisplatin (CDDP)-treated rats was examined.

Methods

Wistar male rats randomly divided into four groups: normal control, tBHQ, CDDP and tBHQ + CDDP received 50 mg/kg b.w./day of tBHQ orally for 14 days while 7 mg/kg b.w of CDDP was administered intraperitoneally on Day 8.

Results

CDDP increased serum biomarkers of hepatic (AST, ALP, ALT, GGT) and renal (creatinine, urea, uric acid, kidney injury molecule 1) function. The levels of nuclear factor erythroid-2-related factor 2 protein and the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities were decreased in liver and kidney. Also, CDDP increased hepatic and renal levels of NF-κB, TNFα, Bax and caspase-3 proteins and decreased hepatorenal levels of Bcl-2 protein in the liver and kidney. Pre-treatment with tBHQ prevented these negative effects.

Significance

Pre-intervention with tBHQ attenuates hepatorenal toxicity of CDDP by dampening oxidative stress, inflammation and apoptosis.

Keywords:

• cisplatin
• tert-butylhydroquinone
• oxidative stress
• inflammation
• apoptosis
• hepatorenal toxicity

Acknowledgements

The authors would like to acknowledge the support of Mr. Umoh Ededet of the Department of Physiology, University of Calabar, Nigeria, during the Laboratory stage of this work. The authors would also like to thank Dr. Effiom Eyo Ita for his assistance during our time in the Molecular Biology and Biotechnology Laboratory, Department of Genetics and Biotechnology, University of Calabar, Nigeria.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This study was funded solely by the authors’ financial contributions.

Author contributions

G.A. Ujah and V.U, Nna conceived and designed the study. All the authors participated in the animal study and performed the biochemical assays. Nna analysed the data sets and prepared all the figures and tables. Ujah, Nna, Ofutet and Ukam wrote the first manuscript draft. All authors edited and approved the final draft of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets used during this study can be obtained from the corresponding authors upon reasonable request.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. This study was funded solely by the authors’ financial contributions..