DOI: 10.21276/ajptr
Tue, 22 Jan 2019

Cyclooxygenase-Independent Mechanism of Nonsteroidal Anti-Inflammatory Drugs

Abdelhady S1*, El Ashmawy N2, El Bahrawy H2, Fouad H3

1.Faculty of Pharmacy, Pharos University, Alexandria, Egypt.

2.Faculty of Pharmacy, Tanta University, Egypt.

3.Faculty of Pharmacy, Alexandria University, Egypt


A potential mechanism of NSAID-mediated anti-proliferative activity may be through the induction of NAG-1. The present study was conducted to investigate the possible role of selective and non-selective COX inhibitors in inflammation associated angiogenesis and apoptosis. Wistar rats were classified into 5 experimental groups; 9 rats each. Group (1) normal control and group (2) injected s.c. with 0.3 % carrageenan in muscle. Groups (3, 4 and 5) were injected s.c. with carrageenan and at the same time given orally 10 mg/Kg Celecoxib, 12.5 mg/Kg Nimesulide or 10 mg/Kg Sulindac, respectively. NAG-1 gene expression in the liver was measured by RT-PCR. Serum TNFα and muscle caspase-3 were measured by ELISA.Immunohistochemical detection of VEGF in the muscle was investigated. Carrageenan untreated rats showed insignificant change in NAG-1 gene expression compared with control group. Serum TNFα and muscle caspase-3 as well as VEGF expression in carrageenan untreated group were significantly increased compared with normal control rats. In Sulindac treated group, NAG-1 gene expression in the liver and muscle caspase-3 were significantly increased compared with Celecoxib and Nimesulide groups. TNFα serum level was significantly decreased in Nimesulide and Celecoxib treated groups compared with carrageenan and Sulindac groups. The examined NSAIDs proved proapoptotic and antiangiogenic effects.

Keywords: NSAIDs,  NAG-1, Csapase-3,TNFα, carrageenan

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