Expression of Concern: Carrageenan‐induced mouse paw oedema is biphasic, age‐weight dependent and displays differential nitric oxide cyclooxygenase‐2 expression

Abstract

Injection of carrageenan 1% (50 μl) in the mouse paw causes a biphasic response: an early inflammatory response that lasts 6 h and a second late response that peaks at 72 h, declining at 96 h. Only mice 7‐ or 8‐week old, weighing 32–34 g, displayed a consistent response in both phases. In 8‐week‐old mice, myeloperoxidase (MPO) levels are significantly elevated in the early phase at 6 h and reach their maximum at 24 h to decline to basal value at 48 h. Nitrate+nitrite (NOx) levels in the paw are maximal after 2 h and slowly decline thereafter in contrast to prostaglandin E2 levels that peak in the second phase at the 72 h point. Western blot analysis showed that inducible nitric oxide synthase (iNOS) is detectable at 6 h and cyclooxygenase 2 (COX‐2) at 24 h point, respectively. Analysis of endothelial nitric oxide synthase (eNOS), iNOS and COX‐2 expression at 6 and 24 h in 3–8‐week‐old mice demonstrated that both eNOS and iNOS expressions are dependent upon the age–weight of mice, as opposite to COX‐2 that is present only in the second phase of the oedema and is not linked to mouse age–weight. Subplantar injection of carrageenan to C57BL/6J causes a biphasic oedema that is significantly reduced by about 20% when compared to CD1 mice. Interestingly, in these mice, iNOS expression is absent up to 6 h, as opposite to CD1, and becomes detectable at the 24 h point. Cyclooxygenase (COX‐1) expression is upregulated between 4 and 24 h after carrageenan injection, whereas in CD1 mice COX‐1 remains unchanged after irritant agent injection. MPO levels are maximal at the 24 h point and they are significantly lower, at 6 h point, than MPO levels detected in CD1 mice. In conclusion, mouse paw oedema is biphasic and age‐weight dependent. The present results are the first report on the differential expressions of eNOS, iNOS, COX‐1 and COX‐2 in response to carrageenan injection in the two phases of the mouse paw oedema. British Journal of Pharmacology (2004) 142, 331–338. doi:

Antioxidant, analgesic and anti-inflammatory activities of the leafy stems of Waltheria indica L. (Sterculiaceae)

“…Carrageenan induced paw edema in a biphasic phenomenon (Swingle, 1974). The initial phase involves the release of mediators such as histamine, serotonin and bradykin in while the late phase is characterized by infiltration of leukocytes and prostaglandins biosynthesis (Posadas et al, 2004). In this study, a significant edema reduction was observed at the first, the third and fifth hours.…”

Phytochemical Screening and Anti-Inflammatory Effect of Marrubium vulgare L. Methanol Extract on Carrageenan-Induced Paw Inflammation in Rats

“…20 Carrageenan-induced rat paw edema, a fully characterized model from past, is a routine test to determine the anti-inflammatory activity and its underling mechanisms. 21 Taking into account the former findings on superior anti-inflammatory and immunomodulatory of antioxidants and diterpenes, it was decided to research on anti-inflammatory activity of M. vulgare on carrageenan-induced paw edema in rats. So, herein, the effect of M. vulgare methanolic extract together with its antioxidant activity in different in vitro models was evaluated, with an approach to introduce a medicinal herb with antiinflammatory properties.…”

Albizia zygia (DC.) Macbr. Hydroethanol Root Extract Exerts Anti-Oedemic and In Vivo Antioxidant Activities in Animal Models

“…Proinflammatory mediators-histamine, serotonin, bradykinin, tachykinins, complement and ROS are responsible for inducing the inflammation (Morris, 2003). Prostaglandins then induce the last phase of the oedema; as a result of the action of inducible forms of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) (Posadas et al, 2004). Preemptive and curative administration of AZEto chicks significantly suppressed the acute local oedema in both treatment protocols.…”

“…and diclofenac (3-30 mg/kg, i.p.) (Roach and Sufka, 2003). Figures 1(a, c) Analysis of the curves with respect to the vehicle control group shows a significant reduction in the mean maximal paw oedema at 2-3 h by AZE (prophylaxis: F 3,20 …”

“…The acute anti-oedemic effect of AZE was investigated in the carrageenan-induced oedema model in chicks (Roach and Sufka, 2003;Abotsi et al, 2012). A volume of 10 μl carrageenan suspension (2 % w / v ) was administered into the chicks' right footpads.…”