Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats

We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg) in male Wistar rats (180-300 g, N = 6) and compared it to free diclofenac (5 or 10 mg/kg) and to the combination of diclofenac (5 or 10 mg/kg) and zinc acetate (1.68 or 3.5 mg/kg). The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip) administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18ºC) for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.

Anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex in rats.

We investigated the anti-inflammatory, antinociceptive and ulcerogenic activity of a zinc-diclofenac complex (5.5 or 11 mg/kg) in male Wistar rats (180-300 g, N = 6) and compared it to free diclofenac (5 or 10 mg/kg) and to the combination of diclofenac (5 or 10 mg/kg) and zinc acetate (1.68 or 3.5 mg/kg). The carrageenin-induced paw edema and the cotton pellet-induced granulomatous tissue formation models were used to assess the anti-inflammatory activity, and the Hargreaves model of thermal hyperalgesia was used to assess the antinociceptive activity. To investigate the effect of orally or intraperitoneally (ip) administered drugs on cold-induced gastric lesions, single doses were administered before exposing the animals to a freezer (-18 degrees C) for 45 min in individual cages. We also evaluated the gastric lesions induced by multiple doses of the drugs. Diclofenac plus zinc complex had the same anti-inflammatory and antinociceptive effects as diclofenac alone. Gastric lesions induced by a single dose administered per os and ip were reduced in the group treated with zinc-diclofenac when compared to the groups treated with free diclofenac or diclofenac plus zinc acetate. In the multiple dose treatment, the complex induced a lower number of the most severe lesions when compared to free diclofenac and diclofenac plus zinc acetate. In conclusion, the present study demonstrates that the zinc-diclofenac complex may represent an important therapeutic alternative for the treatment of rheumatic and inflammatory conditions, as its use may be associated with a reduced incidence of gastric lesions.

Pharmacokinetic profile and adverse gastric effect of zinc-piroxicam in rats.

Complexation of piroxicam with zinc extends its absorption time in rats. The time of peak concentration value for complexed piroxicam was 5.27 hr compared to only 2.56 hr for the uncomplexed agent. Piroxicam and zinc-piroxicam show similar inhibitory effects on carrageenin-induced paw edema. Zinc-piroxicam is less irritating than piroxicam on the gastric mucosa.

Adducts of nitroimidazole derivatives with rhodium(II) carboxylates: syntheses, characterization, and evaluation of antichagasic activities.

Adducts of several rhodium(II) carboxylates with two antiparasitic nitroimidazole ligands were prepared and characterized by elemental microanalysis, thermogravimetry, spectrophotometry (IR, UV, and visible), and proton magnetic resonance. Results of elemental and thermogravimetric analyses were consistent with the general formula Rh2(RCOO)4. 2L (R = aliphatic or aromatic carboxylic groups; L = metronidazole or benznidazole). The reddish-brown color of the adducts as well as their visible spectra suggest axial coordination of the nitroimidazole ligands through nitrogen atoms. NMR spectra indicate N3 as the coordinating atoms. Screening tests performed on cultures of T. cruzi indicate that aliphatic complexes--particularly propionate and acetate adducts--were more active than their aromatic counterparts, the same being observed with benznidazole adducts in relation to their metronidazole analogues. Evaluated for their usefulness as transfusion prophylactic agents against Chagas' disease, propionate derivatives failed to sterilize T. cruzi infected blood. An oral toxicity assay in mice showed mild toxic effects with daily doses of 5 mg/kg for 20 days.

[Studies on guinea pig fed on Brachiaria sp. (Tanner Grass) (author's transl)]. / Estudos sobre cobaias alimentadas com Brachiaria SP. (Tanner grass).

The investigation was developed with 80 female guinea pigs weighing about hundred grams. housed in groups of 15 or 20 animals. The daily treatments were: Brachiaria sp. (Tanner Grass), Brachiaria sp. (Tanner Grass) and meal, Brachiaria decumbens Stapf and the grass Napier. The guinea pigs fed on Brachiaria sp. did not show any symptomas observed in cattle grazing on that graminea. Liver and kidney damage detected upon histological investigation on those animals were different from those observed on intoxicated cattle. The metahemoglobinemic anemia also were not detected on guinea pigs feed on Brauchiaria sp. (Tanner Grass) (1, 2, 3, 7). The urine collected from these animals showed a dark colour, this pigmentation were not found in cattle urine. The dark urine colour of cattle grazing for about one month on "Tanner Grass" was due to hemoblobinuria. The survival time of the guinea pigs feed only with B. decumbens Stapf and the grass Napier was smoller as compared with the animals receiving Brachiaria sp. (Tanner Grass). The syndrome on cattle, the effect on guinea pig added to some other aspect like the fact that plant became more toxic (2) when green and luxurious suggest a similarity with the toxic activity of some species of Brassicas such as B. oleracea var. acephala D.C., B. olerace var. capitata L. and B napus L. (5, 8).