A murine lung fibrosis model has been induced by challenging male Swiss albino mice with a fibrotic dose of bleomycin (10 mg/kg body weight, s.c.) twice weekly for 6 weeks. The model has been characterized and confirmed biochemically, histologically and morphometrically. Keeping in mind that inflammation is the forerunner of lung fibrosis, we have investigated the possible anti-fibrotic effect of meloxicam; a selective COX-2 inhibitor, in this lung fibrosis paradigm. When administered ahead of bleomycin challenge, meloxicam significantly reduced the lung content of hydroxyproline; the backbone of collagen matrix. This was further confirmed by the lower collagen deposition as revealed by histochemical examination of lung sections. Meloxicam had also anti-oxidant effect as shown by increase in lung reduced glutathione (GSH) level and decreases in lung malonedialdehyde (MDA) content and myeloperoxidase (MPO) activity. Besides, meloxicam has shown an apparent angiostatic activity. Histologically, meloxicam lessened lung inflammation and fibrotic changes induced by bleomycin. Taken together, one could conclude that meloxicam has shown anti-fibrotic effect in the bleomycin lung fibrosis model. Apart from its well-known anti-inflammatory potential, this anti-fibrotic action of meloxicam resides most probably, at least partly, in its anti-oxidant and angiostatic effects.

HDL LDL( ) LDL ( ٥ ١،٢،٣،٤ .3-Ethoxycarbonyl-4,6-dimethyl-2(1H)-pyridone I was prepared and converted to the corresponding sodium salt II.The latter reacted with certain chloroacetanilides to afford the corresponding ethers III.In addition 3-cyano-4,6-dimethyl-2(1H)-pyridone IV was prepared and converted to the corresponding potassium salt V which was allowed to react with chloroacetyl and -chloropropionyl derivatives of certain aromatic amines to afford VI.Furthermore, IV was converted to 3-cyano-4,6-dimethyl pyridine-2-thione IX.Potassium salt of the latter upon reaction with -chloroacetyl and -chloropropionyl derivatives of some aromatic amines gave the expected thioethers X. Compounds III 2 , V 4 , X 1 and X 12 were selected for testing for antihyperlipidemic effect and revealed promising hypolipidemic effect on cholesterol, triglyceride, LDL and have no effect on HDL. EXPERIMENTALAll meting points were carried out on Geriffin melting point apparatus and are uncorrected.Elemental analysis were performed on CHN analyzer at the Microanalytical unit, Cairo University, Cairo, Egypt.The IR spectra were recorded on a Pye Unicam SP-1000 IR spectrophotometer at Microanalytical Unit., Cairo University. 1 HNMR spectra were recorded on a Joel 200

The present study was designed to investigate the possible modulator effect of melatonin on uterine estrogen and progesterone receptors in rats as well as the uterine response to oxytocin. Non-pregnant rats were pretreated with melatonin in a dose of 0.8 mg kg(-1) per day for 15 consecutive days. Control animals received the vehicle. The uterus was dissected out and uterine contraction in one horne was recorded in vitro for each animal as a response to oxytocin (0.5 x 10(-11) to 2 x 10(-11)M). The other uterine horne was subjected to estrogen and progesterone receptors detection by immunohistochemical and image analysis techniques. The results reveal a significant reduction (59%) in the number of uterine estrogen receptors with concomitant increase in the progesterone receptors (53%) in melatonin-pretreated rats as compared to the control ones. In addition, our data show an inhibitory effect of melatonin on the uterine contraction as a response to oxytocin (0.5 x 10(-11), 1 x 10(-11), and 2 x 10(-11)M) amounting to 48, 77, and 59.5% reduction, respectively, in the amplitude of contraction as well as 62, 19.9, and 47% reduction in the area under the curve (AUC) of uterine contractions, respectively. The data, so far obtained, may indicate a possible relationship of melatonin-induced modulation of the number of estrogen and progesterone receptors and its inhibitory effect on uterine contraction. These findings merit further investigations on the possible beneficial role of melatonin in a plethora of hormone-dependent uterine disorders.

The antioxidant and pro-oxidant effects of thymoquinone (TQ), a natural main constituent of the volatile oil of Nigella saliva seeds, and a synthetic structurally-related tert-butylhydroquinone (TBHQ), were examined in vitro. Both TQ and TBHQ efficiently inhibited iron-dependent microsomal lipid peroxidation in a concentration-dependent manner with median inhibitory concentration (IC50) values of 16.8 and 14.9 microM, respectively. TBHQ was stronger than TQ as a scavenger of 2,2'-diphenyl-p-picrylhydrazyl radical (DPPH) (IC50 = 5 microM, 200 times more active than TQ) and as a scavenger of hydroxyl radical (OH*) with an IC50 of 4.6 microM (approximately 10 times more active than TQ). TQ was more active than TBHQ as a superoxide anion scavenger with IC50 of 3.35 microM compared to 18.1 microM for TBHQ. Only TBHQ significantly promoted DNA damage in the bleomycin-Fe(III) system. The results suggest that both TQ and TBHQ have strong antioxidant potentials through scavenging ability of different free radicals. Moreover, the data indicate that TQ is acting mainly as a potent superoxide anion scavenger.