TOXIC EFFECTS OF THE EXTRACTS OF EUGENIA UNIFLORA LINN IN RATS

The toxic effects of the leaves of Eugenia uniflora Linn on rats was evaluated by observing abnormal changes in the haemogram including erythron and leukogram, serum biochemical parameters, histopathology, and hexobarbital sleeping time. The leaf extract produced significant increases in the packed cell volume (PCV) haemoglobin concentration and total red blood cell counts (P.05) but did not influence the blood coagulation time. Similarly the leaf extract of Eugenia uniflora produced significant increases (P.05) in the serum activities of alanine aminotransferase and aspartate aminotrasferase. Although the extract did not produce histological lesions of the liver, the increases in liver enzyme activities could be due to incipient liver damage.

Synthesis of some 6-alkylureido-4-aryl-2(1H)-pyridones: further transformations and pharmacological activity

The Michael addition of enaminoesters to coumarins (1) does not lead to the formation of simple adducts 3 but to the rearranged 4-aryl-2-pyridone 4a. Now, N-carbamoylation of the 6-amino-2-pyridone 4a with alkyl isocyanates and further transformation of the corresponding novel ureido-2-pyridone derivatives 6a–g into chromeno[3,4-c]pyridines 5d,g and O-acetyl derivatives 7a–g are reported. All newly synthesized compounds were characterized by means of 1H/13C NMR, MS, IR spectra and elemental analysis. The structure of the ureide 6f and of the N-cyclohexyl-O-acetyl derivative 7g were additionally confirmed by crystal structure determinations. Acute toxicity after intraperitoneal administration, blood clotting time, analgesic activity and the effects on the hexobarbital sleeping time were tested on laboratory animals (compounds 4a, 6a, 6c, 6d and 6g).

The Role of Enzyme Induction on Metabolite Formation of Bis(2-Methoxyethyl) Ether in the Rat

The effect of enzyme induction on the metabolism of the reproductive toxicant bis (2-methoxyethyl) ether (diglyme) was studied in male Sprague-Dawley rats. Rats were given either daily doses of diglyme at 5.1 mmol/kg body wt. by gavage or 0.1% (w/v)phenobarbital (PB) in the drinking water for 22 consecutive days. In one study, a significant reduction in the hexobarbital sleeping time was determined for rats pretreated with diglyme or PB in comparison with that determined for naive rats. In a second study, naive and pretreated rats given single oral doses of14C-diglyme at 5.1 mmol/kg body wt. showed similar urinary 14C excretion patterns. Urinary metabolites were separated and quantified by hplc to evaluate the influence of pretreatment with either diglyme or PB on the 14C-diglyme urinary metabolite profile. The amount of (2-methoxyethoxy) acetic acid, the principal metabolite, was similar for rats given no pretreatment and for rats pretreated with either diglyme or PB. However, both pretreatments resulted in significant increases in the formation of methoxyacetic acid, a recognized reproductive toxicant.

Comparison of the pharmacological properties of pituitary and biosynthetic human growth hormone

Biosynthetic human growth hormone was compared with pituitary human growth hormone and pituitary 22 K in the weight gain and the tibia test. The three preparations were found to be equipotent. Furthermore, the growth hormones were compared in various pharmacological test systems. All three preparations were found to have a marked antidiuretic and antinatriuretic effect in the rat and to cause a significant shortening of the hexobarbital sleeping time in mice. Biosynthetic and pituitary preparations had the same diabetogenic activity in obese mice, and the growth hormones did not differ with respect to pharmacological profiles in the test systems applied.

Tryptophan pyrrolase in haem regulation. The relationship between the depletion of rat liver tryptophan pyrrolase haem and the enhancement of 5-aminolaevulinate synthase activity by 2-allyl-2-isopropylacetamide

Rat liver tryptophan pyrrolase haem is maximally depleted at 30 min after administration of a 400 mg/kg dose of 2-allyl-2-isopropylacetamide. This depletion lasts for 24 h, by which time 5-aminoleevulinate synthase activity becomes maximally enhanced. 2. though the above maximum depletion of pyrrolase haem (at 0.5h) is also produced by a 100 mg/kg dose of the porphyrogen, this does not enhance synthase activity at 24 h. It and smaller doses, however, cause a smaller but earlier enhancement of synthase activity (maximum at 2 h) and produce a similarly short-lived deplation of pyrrolase haem. 3. The depletion of pyrrolase haem and the enhancement of synthase activity by the porphyrogen are inhibited by compound SKF 525-A and phenazine methosulphate, and are potentiated by nicotinamide but not by phenobarbitone. Phenazine methosulphate and nicotinamide also exert opposite effects on hexobarbital sleeping-time. 4. 2-Allyl-2-isopropylacetamde also the depletes pyrrolase haem in vitro. It does so in liver homogenates of control rats in the presence, and in those of phenobarbitone-treated rats in the absence of added NADPH. 5. A discussion of the present results in relation to previous work with other haemoproteins suggests that, whereas cytochrome P-450 (haem) is primarily involved in the production of the active (porphyrogenic) metabolite(s) of 2-allyl-2-isopropylacetamide, the haem pool used by tryptophan pyrrolase may play an important role in the effects of this compound on haem biosynthesis.