Inflammation Carrageenan

The observation that copper complexes have anti-inflammatory activity has been confirmed and extended by many others with reports that the same and additional copper complexes listed in Table 6.4 have anti-inflammatory activity in an even greater variety of animal models of inflammation carrageenan, kaolin, dextran, hydroxyapatite and concanavolin A (Con A) paw oedemas, cotton wad granuloma, polyarthritis and ultraviolet erythema. Data presented for copper complexes and their parent ligands in all subsequent reports when compared on a molar basis also show marked increases in anti-inflammatory... 

To study the effects of iron overloading on inflammatory cells, Muntane et al. [186] investigated the effect of iron dcxtran administration on the acute and chronic phases of carrageenan-induced glanuloma. It was found that iron dcxtran increased the iron content in plasma and stores, and enhanced lipid peroxidation and superoxide production by inflammatory cells. At the same time, iron dcxtran had a beneficial effect on recovery from the anemia of inflammation. It has been suggested that iron overload may affect nitric oxide production in animals. For example, alveolar macrophages from iron-overloaded rats stimulated with LPS or interferon-7 diminished NO release compared to normal rats [187]. 

A group from La Jolla Pharmaceuticals has released data on their novel hydrazines in recent scientific [20,59,60] and patent literature [61,62], A series of arylallyl hydrazines (e.g., 8 and 9) were shown to be potent, irreversible inhibitors of rat and human SSAO/VAP-1 [59]. LJP-1207 (8, IC50 = 2nM, human) was evaluated in a series of in vivo inflammation models. Significant efficacy was observed in a mouse ulcerative colitis, mouse LPS-induced septic shock, and the rat carrageenan foot models [20], in a mouse model that resembles human multiple sclerosis [63], and in a transient forebrain ischemia model in estrogen-treated ovariectomized female rats [60]. 

L-701,324 has been shown to reverse the inflammation-induced mechanical hyperalgesia in rats without affecting the accompanying carrageenan-induced paw edema (Laird et al., 1996). 

Wu WP, Hao JX, Halldner-Henriksson L, Xu XJ, Jacobson MA, Wiesenfeld-Hallin Z, Fredholm BB (2002) Decreased inflammatory pain due to reduced carrageenan-induced inflammation in mice lacking adenosine A3 receptors. Neuroscience 114(3) 523-527... 

Primary screening data correlated with the in vivo results. Four selected hits, when tested on a carrageenan induced rat paw edema model of acute inflammation and were bioavailable and pharmacologically active, reducing swelling of the paw (data not shown here). The efficacies of the extracts were measured by calculating the reduction in swelling as compared to the vehicle-treated control. Aspirin was used as a positive control for anti-inflammatory activity. These observations validated the potential use of the hits discovered in the RT-PCR assay for the in vivo anti-inflammatory applications. 

Garry, M. G., Richardson, J. D., and Hargreaves, K. M. (1994). Carrageenan induced inflammation alters the content of i-cGMP and i-cAMP in the dorsal horn of the spinal cord. Brain Res. 646, 135-139. 

The in vivo assays for the Cox-2 inhibitors are essentially those used historically for NSAIDs to evaluate both their desired effects on inflammation, pain, and fever and their undesired effects, mainly on GI lesions. The primary in vivo assay for anti-inflammatory efficacy is the carrageenan-induced rat paw edema assay, and 51 Cr fecal excretion is used to test for damage to the intestinal mucosa in rats and in squirrel monkeys. Additional tests for efficacy are the endotoxin-induced pyresis in rats and squirrel monkeys for control of fever and the carrageenan-induced rat paw hyperalgesia assay for analgesic efficacy. These in vivo assays have been described (Chan et al., 1995 Chan et al., 1997). The rat... 

It has been consistently and repeatedly reported that the inflammatory process is accompanied by a seemingly paradoxical enhancement of the antinociceptive activity of opioids [152], For example, carrageenan-induced inflammation elicited a 30-fold increase in the ability of morphine to inhibit evoked activity of C-fibers [153]. The antinociceptive effect of morphine was similarly enhanced in arthritic rats [154], Further, the effect of ITH DAMGO... 

Curcuminoids and other constituents of turmeric are well known for their antiinflammatory activity. Turmeric extract, volatile oils from turmeric and curcuminoids were reported to possess this property in different experimental models of inflammation in mice, rats, rabbits and pigeons (Arora et ah, 1971 Ghatak and Basu, 1972 Chandra and Gupta, 1972). Thus, curcuminoids are effective against carrageenan-induced oedema in rats (Srivastava et al.,... 

The hydrophilic members of the 3-hydroxypyridin-4-one family, e.g. CP20 (Structure 4), also possess anti-inflammatory activities in the acute carrageenan-pleurisy model when presented at relatively high doses [66], Although iron chelators undoubtedly possess anti-inflammatory properties, high concentrations are necessary and selective direction of these molecules to the site of inflammation presents a major problem. 

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