Abstract
Apart from reducing the acid secretion, omeprazole inhibits activation of the nuclear factor-κB, release of inflammatory cytokines, and chemotaxis of neutrophils. These mechanisms prompted us to evaluate antineuropathic effect of omeprazole in the chronic constriction injury (CCI)-induced rat model of neuropathic pain and LPS mediated ROS-induced U-87 cells. Omeprazole at 50 mg/kg/day/oral for 14 days significantly reduced the intensity of neuropathic pain estimated as paw withdrawal latency, withdrawal pressure threshold and restored the motor nerve conduction velocity in the constricted nerve, when compared with respective groups. The histological findings revealed the protective effect of omeprazole against the CCI-induced damage. Omeprazole significantly decreased the levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) as compared to their respective control groups. It also reduced the oxidative stress by up regulating the SOD, catalase activity and decreasing MDA content. Similarly, in-vitro study, LPS mediated ROS-induced U-87 cells, omeprazole reduced the oxidative stress as well as the release of TNF-α, IL-1β and IL-6. Altogether, these results suggest that, neuroprotective effect of omeprazole is mediated through preventing release of proinflammatory cytokines, augmenting endogenous anti-oxidant defense system, and maintain the structural integrity of sciatic nerve from the CCI-induced structural damage and inflammatory changes.
Highlights
Neuropathic pain is a debilitating condition arising from injury to the somatosensory neurons which triggers the development of allodynia and hyperalgesia[1]
The present study demonstrated that in addition to its pump inhibitors (PPIs) effect, omeprazole exhibits a protective effect by improving nerve conduction velocity and paw withdrawal latency (PWL); restoring the endogenous antioxidant system; preventing the increased level of inflammatory cytokines such as TNF-α, IL-1βand IL-6; reducing lipid peroxide metabolism; and preserving the structure and morphology of sciatic nerve via inhibiting proinflammatory cytokines
Our study provides direct evidence that the cytokines signaling pathway plays a key role in regulating oxidative stress and subsequent nerve injury in constriction injury (CCI)-induced neuropathic pain
Summary
Neuropathic pain is a debilitating condition arising from injury to the somatosensory neurons which triggers the development of allodynia and hyperalgesia[1]. Correspondence and requests for materials should be addressed to www.nature.com/scientificreports/ In preview of such repositioning approach, many recent preclinical and clinical evaluations have highlighted diverse effects of omeprazole other than its proton pump inhibitory actions. Omeprazole reduces the LPS-induced release of TNF-αand IL-6 from the human microglial cell culture and human monocytes culture in vitro This effect is proposed to contribute to the neuroprotective effect of omeprazole against the microglial and monocytic toxicity[14]. It has been revealed to reduce the IFN-γinduced astrocyte toxicity and phosphorylation of STAT314 It inhibits the carrageenan-induced acute paw inflammation in rats[10,15]. The present study was designed to investigate the effects of chronic oral administration of omeprazole employing the CCI-induced neuropathic pain in rats
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