In the formalin test ketorolac at a dose

In the formalin test, ketorolac at a dose levels of 15 mg/kg, 30 mg/kg and 60 mg/kg exerted better analgesic effect demonstrated at the late phase of the nociceptive response which may be due to its peripheral anti-inflammatory effect. Following irradiation, treatment with ketorolac exerted a more powerful analgesic activity. Thus, our results suggest the presence of synergism between irradiation and NSAID (ketorolac) at both phases. However, prostaglandin E2 levels for all groups did not significantly changed from normal control. This may be explained by the finding of Gilroy et al. [32,33] who revealed that there were differential contributions of COX-1 and COX-2 derived prostanoids in models of acute and chronic inflammation. In contrast, another study of Brzozowski et al. [34] reported that COX-1 and COX-2 products act synergistically in healing of ischemia reperfusion induced gastric lesions. Our results further indicate that, both irradiation and ketorolac analgesic effects were associated with the increase in serotonin content of the O4I1 stem area of the animals. These results suggesting that ketorolac may have an effect on brain serotonin which causes the reduction in the duration of licking response in both phases. We studied the safety of ketorolac administration to animals exposed to fractionated gamma irradiation. Our results showed that the acute LD50 of ketorolac was decreased in the irradiated animals as compared to the LD50 in normal animals which revealed increased toxicity of irradiated animals. This may be attributed to cellular change and the high sensitivity of the body organs after exposure to radiation [2]. In the present study, the activity of serum ALT was augmented. The elevation of the liver enzyme ALT was in agreement with Franken et al. [35] and El-Gabry et al. [36] They demonstrated that the increase in serum enzymes following radiation exposure may be a response to the oxidative stress and damage of liver cells and consequently the elaboration of its intracellular enzymes into the blood stream [37]. The recorded elevations could be also due to a hypoxia state in the parenchymal liver cells and increased permeability of cell membrane or mitochondrial membrane causing the release of intracellular enzymes into circulation [38]. These findings were confirmed by the histological examination of the liver tissue of rats exposed to irradiation which revealed dilatation of hepatic sinusoids associated with few inflammatory cells infiltration. Gamma irradiation stimulates acute phase response essential for generation and limitation of inflammation. This response is usually orchestrated through cytokines and hepatocyte stimulatory factors associated with characteristic metabolic changes in protein synthesis [39]. This may explain the elevation of globulin level when ketorolac was administered for 7 days to irradiated rats. Ketorolac administration for 7 days to irradiated rats was also associated with lowering of serum albumin level. This effect may be attributed to liver injury that lead to enhanced degradation of liver cells which are responsible for albumin synthesis as well as the enhanced loss of albumin through the gastrointestinal tract [40] as a result of free radicals generation which induce damage to the gastrointestinal mucosa and loss of albumin. Our study showed that there was a deterioration of renal function as manifested by the elevation of serum creatinine level associated with congestion of renal blood vessels demonstrated in the histopathological examination after radiation exposure. Furthermore, serum urea and BUN levels were also increased which may be due to the ammonia formed by deamination of amino acids in the liver, which subsequently is converted to urea. As creatinine is formed largely in muscles and occurs freely in blood, its increased levels in serum serve as an index of renal function impairment [41]. Single dose of ketorolac prevented functional and structural changes demonstrated in kidney and caused by irradiation. Furthermore, ketorolac administration for 7 days to irradiated rats prevents the vacuolization of epithelial cells and perivascular edema recorded in the histopathological examination.