Differential Effects of Selective Cyclooxygenase (COX)-1 and COX-2 Inhibitors on Anorexic Response and Prostaglandin Generation in Various Tissues Induced by Zymosan

Abstract

We have shown that anorexic response is induced by intraperitoneal injection of zymosan in mice, although the role of prostaglandins in this response is relatively unknown as compared with lipopolysaccharide (LPS)-induced anorexic response. Indomethacin (0.5 and 2.0 mg/kg), a non-selective cyclooxygenase (COX) inhibitor, as well as meloxicam (0.5 mg/kg), a selective COX-2 inhibitor, but not FR122047 (2.0 mg/kg), a selective COX-1 inhibitor, attenuated zymosan-induced anorexia. Zymosan injection elevated COX-2 expression in brain and liver but not in small intestine and colon. Meloxicam (0.5 mg/kg) and FR122047 treatment (2.0 mg/kg) similarly suppressed the generation of brain prostaglandin E 2 (PGE 2 ) and peritoneal prostacyclin (PGI 2 ) upon zymosan injection. PGE 2 generation in liver upon zymosan injection was suppressed by meloxicam (0.5 mg/kg) but not by FR122047 treatment (2.0 mg/kg). Our observations suggest that COX-2 plays an important role in zymosan-induced anorexia, which is a similar feature in LPS-induced anorexic response. However, non-selective inhibition by selective COX-1 and COX-2 inhibitors of brain PGE 2 generation upon zymosan injection does not support the role of COX-2 expressed in brain in zymosan-induced anorexic response. PGE 2 generation in liver may account for peripheral role of COX-2 in zymosan-induced anorexic response.

CRTH2, a prostaglandin D2 receptor, mediates depression-related behavior in mice

“…Recently, we found that central CRTH2 but not DP1 regulates emotional aspects of lipopolysaccharide (LPS)-and tumor-induced sickness behaviors [16]. Given that LPS-induced sickness behavior critically involves the COX-2-PG pathway [17][18][19][20][21], PGD 2 -CRTH2 is likely to modulate sickness behavior by regulating COX-2-mediated signaling in the brain [16]. Furthermore, several lines of evidence suggest that sickness behavior and depression share many of the same symptoms and common inflammatory pathways [22].…”

Kamikihito Ameliorates Lipopolysaccharide-Induced Sickness Behavior <i>via</i> Attenuating Neural Activation, but Not Inflammation, in the Hypothalamic Paraventricular Nucleus and Central Nucleus of the Amygdala in Mice

“…25) In addition, an increase in prostaglandin synthesis through inflammation-induced COX-2 in the CNS is also implicated in sickness behavior. 13,22,26,27) We previously reported that genipin, a main constituent of Gardeniae Fructus, is one of the component herbs of KKT, ameliorated LPS-induced sickness behavior and inflammation in the hypothalamus and amygdala 2 h after LPS administration. 15) Therefore, it seemed likely that KKT would also attenuate LPS-induced inflammation in the hypothalamus and amygdala 2 h after LPS administration.…”

Cattle Bile Aggravates Diclofenac Sodium‐Induced Small Intestinal Injury in Mice

“…For the determination of PGE 2 content, ethanol extracts from the small intestine prepared as described above were dried under nitrogen gas. PGE 2 content in the samples was determined using enzyme immunoassay kits (Cayman Chemicals, Ann Arbor, MI) [21]. …”

“…The specimens were blotted onto dry filter papers to remove excess water. The expression levels of COX-1 and COX-2 in the small intestine were determined by western blot analysis as described previously [21]. …”