Renal oxidative stress and renal CD8⁺ T-cell infiltration in mercuric chloride-induced nephropathy in rats: role of angiotensin II

Abstract

Mercuric chloride (HgCl₂) induces kidney damage, in part, through oxidative stress. A role for angiotensin II (Ang II) in pro-inflammatory events in a model of acute HgCl₂-induced nephropathy was reported. Ang II is a potent oxidative stress inducer; however, its role in oxidative/anti-oxidative events in HgCl₂-induced nephropathy remains unknown. The aim of this study was to determine the role of Ang II in the oxidative stress and renal infiltration of CD8⁺ T-cells after an acute HgCl₂ intoxication. Three groups of Sprague Dawley rats were treated with a single subcutaneous dose of 2.5 mg/kg HgCl₂: for 3 days prior to and for 4 days after that injection, rats in one group received Losartan (30 mg/kg), in another group Enalapril (30 mg/kg) or normal saline in the last group. Two other groups of drug-treated rats received saline in place of HgCl₂. A final group of rats received saline in place of HgCl₂ and the test drugs. All treatments were via gastric gavage. At 96 h after the vehicle/HgCl₂ injection, blood and kidney samples were harvested. Renal sections were homogenized for measures of malondialdehyde (MDA), reduced glutathione (GSH) and catalase activity. Frozen sections were studied for the presence of superoxide anion () and CD8⁺ T-cells. HgCl₂-treated rats had increased interstitial and tubular expression of , high levels of MDA, normal catalase activity and GSH content, increased levels of interstitial CD8⁺ T-cells and an increased percentage of necrotic tubules. Anti-Ang II treatments diminished the HgCl₂-induced increases in interstitial , CD8⁺ T-cells and tubular damage and increased catalase and GSH expression above that due to HgCl₂ alone; the HgCl₂-induced high MDA levels were unaffected by the drugs. These data provide new information regarding the potential role of Ang II in the oxidative stress and renal CD8⁺ T-cell infiltration that occur during HgCl₂ nephropathy.

Keywords:

• Angiotensin II
• Enalapril
• kidney
• Losartan
• mercuric chloride
• oxidative stress

Acknowledgements

We thank the Instituto de Investigaciones Clinicas “Dr. Americo Negrette”, Facultad de Medicina (Universidad del Zulia, Venezuela) that provided support for this study. The Institution was not involved in the study design, collection, analysis and interpretation of data, writing of the report or in the decision to submit the article for publication.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.