Effects on intestinal microflora, gastrointestinal tolerability and antiinflammatory efficacy of diclofenac and nitrofenac in adjuvant arthritic rats.

Since it is known that nitric oxide plays an important protective role in maintaining the tissue integrity and is cytotoxic for invasive micro-organisms, diclofenac and a new original diclofenac-derivate, nitrofenac (containing the nitric oxide group), was administered at doses of 0.3 and 3 mg kg-1 per os to adjuvant arthritic rats. At the 14th, 21st and 28th days after arthritis induction, the antiinflammatory efficacy and the effects on intestinal microflora of the two drugs were evaluated; moreover, at the end of the study period, the gastrointestinal tract was examined macroscopically for any presence of lesions. Daily oral administration of diclofenac and nitrofenac at 3 mg kg-1 markedly and significantly inhibited arthritis development until the end of the study period. Some significant changes were observed in anaerobic and Gram-negative bacterial flora, particularly the total disappearance, in all treated rats, of Escherichia coli 1, also 7 days after the last drug administration. Finally, no ulcers or severe damage were observed macroscopically with either drug, even if some alterations in the mucosa and haemorrhagic effusions were more evident in rats treated with diclofenac at 3 mg kg-1. In conclusion, in this chronic model a similar therapeutic efficacy of diclofenac and nitrofenac is shown in arthritic rats. The better gastrointestinal tolerability observed in nitrofenac-treated rats could be attributed to the release of nitric oxide.

Gastrointestinal effects of single and repeated doses of ferrous sulphate in rats.

The gastrointestinal effects of single and repeated administration of ferrous sulphate was evaluated measuring faecal flora modifications and histology of stomach and duodenum of the rat. The acute experiments showed reversible histopathological lesions of stomach and duodenum with iron deposition and increase in faecal Cl. perfringens toxin after treatment with a high dose of FeSO4. The chronic experiment at lower doses showed no relevant histological damage, some iron deposition and strong alterations in faecal flora. A strong impact of oral FeSO4 on gastrointestinal environment was demonstrated.

Desferrioxamine potentiated SOD antiinflammatory activity in rat adjuvant arthritis: role of iron and bacterial toxins.

In this paper we studied the modulating inflammatory activity of iron in the adjuvant arthritis, taking indomethacin as a standard antiinflammatory drug and a superoxide dismutase derivative (MPEG-SOD) as a scavenger of free radicals. Moreover, we evaluated the changes in potential intestinal pathogens requiring iron for growth, in order to study the role of bacteria in the altered gastrointestinal functions observed during arthritis. We observed a 50% arthritis inhibition on the 14th day with MPEG-SOD plus desferrioxamine, a significant decrease in serum iron in arthritic rats compared to controls, and a significant Cl. perfringens increase on the 28th day in the presence of MPEG-SOD. Our data demonstrate that hypoferremia, in arthritis, is a protective mechanism overall in the early phase and could protect the intestinal tract by inhibiting the development of potential pathogens.

The anesthetized guinea pig as a versatile pharmacological test object.

An anesthetized animal preparation suitable for testing the pharmacological properties of a variety of potentially effective new compounds is described. The advantage of such a procedure as an useful tool to determine the pharmacodynamic profile of the new agents is described in detail.