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Agha, A. M., A. S. el-Khatib, S. A. Kenawy, and M. T. Khayyal, "The influence of carbon tetrachloride-induced liver damage on the inflammatory reaction elicited by carrageenan and its treatment with diclofenac.", Pharmacological research, vol. 32, issue 1-2, pp. 75-84, 1995 Jul-Aug. Abstract

The effect of impaired hepatic function on the development of the inflammatory process as well as on treatment with diclofenac was investigated. Carbon tetrachloride was used to induce liver injury and the elevation of serum transaminases was taken as evidence for impaired hepatic function. The carrageenan-induced rat hind paw oedema and the granuloma pouch were chosen as models of inflammation. The results of the study revealed that: (1) The intensity of inflammation in both models was markedly attenuated in CCl4-treated animals. (2) Serum total proteins were decreased in liver-injured animals particularly in acute experiments. (3) In liver-injured groups diclofenac showed more pronounced anti-inflammatory activity in chronic experiments, but not in acute ones. (4) Neither CCl4 nor diclofenac affected the levels of histamine and serotonin in the granuloma pouch exudate. The level of prostaglandins was decreased in CCl4 and in diclofenac-treated animals. At the same time, the leukotriene content was elevated. The mechanism by which CCl4 induced liver injury attenuates inflammatory response to carrageenan is not entirely understood. Its effect on protein metabolism and extravasation as well as on PG synthesis could play a possible role. Decreased drug metabolism may be, at least in part, responsible for the enhanced response of diclofenac in the cases of liver-injured animals. Dose adjustment of the drug in case of hepatic impairment might be necessary.

Mansour, M., A. S. el-Khatib, and O. El-Ahmady, "INHIBITED GENERATION OF LEUKOTRIENES FROM STIMULATED HUMAN LEUKOCYTES BY THE AQUEOUS EXTRACT OF PROPOLIS", Bull. Fac. Pharm. Cairo Uni, vol. 33, issue 2, pp. 75-79, 1995.
Khayyal, M. T., A. S. el-Khatib, M. El-Ghazaly, and A. Hatem, "Inhibition of leukotriene release by mofebutazone: a possible clinical advantage.", International journal of clinical pharmacology research, vol. 13, issue 5, pp. 255-61, 1993. Abstract

The isolated perfused lung preparation from actively sensitized guinea-pigs was used; after it was challenged with antigen, mediators such as histamine, prostaglandins and leukotrienes were released into the lung effluent. It was found that treatment of the perfused lungs before and during challenge with mofebutazone (10 micrograms/ml) inhibited the immunological release of prostaglandins as well as leukotrienes. Phenylbutazone, on the other hand, at the same dose level inhibited the release of prostaglandins, whereas the release of leukotrienes was much less affected by the drug. Histamine release was not altered by either drug. When clinically mofebutazone tablets (300 mg) were given as an analgesic twice daily for 15 days to a number of asthmatic volunteers including 3 aspirin-sensitive individuals, there was no increase in the incidence or intensity of the asthmatic attacks, even in the aspirin-sensitive patients. Pulmonary ventilatory functions which showed a certain obstructive pattern were not worsened by the treatment and even tended to be somewhat improved.

Khattab, M. M., A. M. Moustafa, O. A. Al-Shabanah, and A. S. el-Khatib, "INVOLVEMENT OF NITRIC OXIDE IN CARBON TETRACHLORIDE-INDUCED ACUTE HEPATOTOXICITY IN MICE", Res. Commun. Pharmacol. Toxicol, vol. 7, issue 1-2, pp. 53-64, 2002.