The impact of vitamin C on the relationship among inflammation, lipid peroxidation and platelet activation during analgesic nephropathy in rats

Nikola Hadzi-Petrushev; Dine Mitrov; Vladimir Kostovski; Mitko Mladenov

doi:10.1515/jbcpp-2016-0150

Article

The impact of vitamin C on the relationship among inflammation, lipid peroxidation and platelet activation during analgesic nephropathy in rats

Nikola Hadzi-Petrushev , Dine Mitrov , Vladimir Kostovski and Mitko Mladenov

Published/Copyright: August 3, 2017

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 28 Issue 5

Abstract

Background:

Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F_2α (8-iso-PGF_2α) and platelet activation as well as the relative contribution of the pro-inflammatory markers interleukin (IL)-1β and tumor necrosis factor-α (TNF-α) in enhanced 8-iso-PGF_2α biosynthesis, as a complementary onset during analgesic nephropathy induced by chronic treatment with paracetamol. The protective effects of vitamin C on the aforementioned settings are also investigated.

Methods:

Analgesic nephropathy was induced in Wistar rats. Renal function markers and the activity of antioxidant enzymes were determined spectrophotometrically. Immunoassays were used to measure the pro-inflammatory markers and the markers of lipid peroxidation and platelet activation.

Results:

The chronic treatment with paracetamol led to renal dysfunction, represented by the elevation of plasma urea and creatinine and the decline in the enzymatic antioxidant status, but did not cause a significant increase in TNF-α and IL-1β. The paracetamol-induced lipid peroxidation and enhanced production of 8-iso-PGF_2α was not sufficient to cause changes in platelet activation represented by the level of 11-dehydro thromboxane B₂.

Conclusions:

Our results suggest that oxidative stress cannot circumvent the need of stimulation by circulatory cytokines in order to induce inflammatory response and changes in platelet activation during analgesic nephropathy. Vitamin C proved to be beneficial in restoring the renal function markers to normal, increasing the renal enzymatic antioxidant potential, inhibiting lipid peroxidation, and lowering cytokine production and 11-dehydro thromboxane B₂ excretion. The observed effects of vitamin C offer support for its potential use as protective treatment in cases of chronic paracetamol overdose.

Keywords: inflammation; lipid peroxidation; nephropathy; paracetamol; platelet activation; vitamin C

Corresponding author: Nikola Hadzi-Petrushev, PhD, Assistant Professor of Physiology, Department of Physiology, Faculty of Natural Sciences and Mathematics, Institute of Biology, “Ss. Cyril and Methodius” University, Skopje, Republic of Macedonia, Phone: +389 2 3249 605, Fax: +389 2 3228 141

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-10-4

Accepted: 2017-6-5

Published Online: 2017-8-3

Published in Print: 2017-9-26

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Articles in the same Issue

https://doi.org/10.1515/jbcpp-2016-0150

Keywords for this article

inflammation; lipid peroxidation; nephropathy; paracetamol; platelet activation; vitamin C