Abstract
In the present study, we investigated the potential beneficial impact of the addition of antioxidant supplements to diclofenac regimen in a model of carrageenan-induced paw. Rats were treated daily with antioxidants, that is, a-lipoic acid (50 mg/kg), selenium (2.5 mg/kg), vitamin C (1 g/kg), vitamin E (300 mg/kg), or zinc (25 mg/kg) on seven successive days and then received a single treatment with diclofenac or saline before carrageenan was injected to induce paw inflammation. The results indicated that these combinations did not significantly affect the percentage inhibition of paw edema caused by diclofenac alone; however, some combination treatments ameliorated signs of concomitant oxidative stress (such as alterations in plasma malondialdehyde (MDA) levels, hemolysate reduced glutathione levels, and erythrocytic superoxide dismutase enzyme activities) imparted by diclofenac alone. In some cases, few tested antioxidants in combination with diclofenac resulted in increased plasma levels of interleukin- (IL-) 6 and C-reactive protein (CRP). In conclusion, the results of these studies suggested to us that the added presence of natural antioxidants could be beneficial as standard anti-inflammatory therapeutics for a patient under diclofenac treatment, albeit that these effects do not appear to significantly build upon those that could be obtained from this common anti-inflammatory agent per se.
Highlights
During the last decade, great advances have been made for understanding the pathophysiology of inflammation and the involvement of reactive oxygen species (ROS) in its pathogenesis
While we focused on the potential for these agents to reduce any undesired toxicities from the chronic use of diclofenac, we were mindful that these studies could provide information that would allow for an unintended benefit potentially allowing for a decrease in the effective dose of diclofenac needed by a patient and a subsequent decrease in the risk of development of adverse effects
The inhibitory effects imparted by the combinations were significantly no better than the diclofenac alone; only in the case of combination with Zn the inflammation was reduced better than the outcome induced by diclofenac alone
Summary
Great advances have been made for understanding the pathophysiology of inflammation and the involvement of reactive oxygen species (ROS) in its pathogenesis. Inflammation is a complex defense mechanism in which leukocytes migrate from the vasculature into damaged tissues to destroy the agents that can potentially cause tissue injury [1]. Millions of people all over the world are suffering from inflammatory disorders, making them use huge amounts of anti-inflammatory agents (i.e., diclofenac, a nonselective cyclooxygenase [COX] inhibitor) for many years in their lives. A subsequent oxidative stress (OS) predominates when production of ROS exceeds the capacity of cellular antioxidant defenses to remove these toxic species [2]. Due to their high reactivity, ROS are potentially causing damage to biomolecules such as DNA, lipids, and proteins. There is increasing interest in examining the potential benefits from providing patients antioxidants, such as αlipoic acid (α-LA), selenium (Se), Vitamin C (Vit C), Vitamin E (Vit E), and zinc (Zn)-supplements, as “add-ons” to their diclofenac regimen
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