Protective effects of remote ischemic preconditioning against cisplatin-induced hepatotoxicity in rats

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Abstract

Background
As cisplatin (CP) remains one of the most effective antineoplastics used in chemotherapy, strategies to protect tissues against CP toxicity are of clinical interest. A major dose-limiting side effect in CP-based chemotherapy is hepatotoxicity. Remote ischemic preconditioning (rIP) represents a noninvasive model for organ protection. The present study was designed to examine, , the CP-induced hepatic injury and to find the protective probability of rIP in this model in relation to an inflammatory mechanism and the hepatic energetic activity.
Materials and methods
Twenty-four adult male albino rats were divided equally into three groups that were treated as follows: (i) control group, (ii) CP group (single intraperitoneal injection of CP 7 mg/kg body weight), and (iii) preconditioned group. rIP was induced with three 10-min ischemia/10-min reperfusion cycles of the right hind limbs just before CP injection. The animals were killed 14 days after the treatment. Among all groups, the gene expression of , , an autophagy marker and fatty acid-binding protein was assessed by real-time reverse transcription-PCR in the rat liver tissue, in addition, the serum levels of liver enzymes alanine aminotransferase and aspartate transaminase were measured.
Results
CP induced an increase in hepatic NF-κB and mitochondrial dysfunction as reflected by the decrease in and a significant reduction in the mitochondrial clearance mechanism: mitochondrial autophagy, which is known as mitophagy. Further, CP significantly decreased the expression of the main protein involved in fatty acid transport, , which is also considered an effective endogenous antioxidant. However, these alterations were ameliorated in preconditioned rats.
Conclusion
We can assume that the alleviative outcome of rIP in CP-induced hepatotoxicity could be because of induction of anti-inflammatory and antioxidant responses associated with the upregulation of mitochondrial function.

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