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

Publisher: Walter de Gruyter Country of Publication: Germany NLM ID: 9101750 Publication Model: Print Cited Medium: Internet ISSN: 2191-0286 (Electronic) Linking ISSN: 07926855 NLM ISO Abbreviation: J Basic Clin Physiol Pharmacol Subsets: MEDLINE

Publication: Jun. 2011- : Berlin : Walter de Gruyter
Original Publication: London, England : Freund Pub. House, c1990-

Analgesics/*adverse effects ; Ascorbic Acid/*pharmacology ; Inflammation/*drug therapy ; Kidney Diseases/*chemically induced ; Kidney Diseases/*drug therapy ; Lipid Peroxidation/*drug effects ; Platelet Activation/*drug effects; Acetaminophen/adverse effects ; Animals ; Antioxidants/metabolism ; Biomarkers/metabolism ; Cytokines/metabolism ; Dinoprost/analogs & derivatives ; Dinoprost/metabolism ; Inflammation/metabolism ; Interleukin-1beta/metabolism ; Kidney Diseases/metabolism ; Male ; Oxidative Stress/drug effects ; Rats ; Rats, Wistar ; Thromboxane B2/analogs & derivatives ; Thromboxane B2/metabolism ; Tumor Necrosis Factor-alpha/metabolism

Background: Oxidative stress and inflammation are involved in the pathogenesis of paracetamol-induced renal damage. This study examines the relationship between 8-iso-prostaglandin F2α (8-iso-PGF2α) 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-PGF2α 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-PGF2α 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

0 (Analgesics)
0 (Antioxidants)
0 (Biomarkers)
0 (Cytokines)
0 (Interleukin-1beta)
0 (Tumor Necrosis Factor-alpha)
27415-26-5 (8-epi-prostaglandin F2alpha)
362O9ITL9D (Acetaminophen)
54397-85-2 (Thromboxane B2)
67910-12-7 (11-dehydro-thromboxane B2)
B7IN85G1HY (Dinoprost)
PQ6CK8PD0R (Ascorbic Acid)

Date Created: 20170804 Date Completed: 20180514 Latest Revision: 20180514

20221213

10.1515/jbcpp-2016-0150

28771433