Abstract Comparing macrophage-derived cytokine and
nitric oxide (NO) profiles in type I and type II diabetes
mellitus (DM); and determining whether thymoquinone
(TQ) has any modulatory effect were the main objectives
of the present study. Peritoneal macrophages have been
collected from Otsuka Long-Evans Tokushima Fatty
(OLETF) as a model for type II DM and its control Long-
Evans Tokushima Otsuka (LETO) rats, as well as from
streptozotocin (STZ)-injected LETO ones as a model for
type I DM. The cells were cultured and incubated with or
without TQ (10 μM) in the absence or presence of
lipopolysaccharide (LPS; 1 μg/ml). The same parameters
have been also assessed in sera of the used animals with or without TQ treatment (3 mg/kg) under both LPS-stimulated (10 mg/kg) and unstimulated conditions. Nitrite, IL-1β and TNF-α were significantly higher in macrophage supernatants and sera of the acutely affected STZ-LETO
rats either with or without LPS stimulation compared to
corresponding controls. On the other hand, chronically
diabetic OLETF rats’ macrophage supernatants showed
significant decreases of IL-1β and TNF-α levels upon LPS
stimulation or even without stimulation (IL-1β); and
insignificant increase in nitrite concentration, which
turned significant upon LPS stimulation. Sera of these animals, however, showed significant increase in TNF-α
level. TQ normalised the elevated nitrite and cytokine profiles both in vitro and in vivo, yet had no significant effect
on the already decreased parameters in chronically affected OLETF rats. These data suggest that there is a tendency for macrophage inflammatory products to increase in acute type I and to decrease in chronic type II DM; and that TQ has the potential to normalise the elevated levels of these macrophage-derived inflammatory mediators. |
