Biomedical subjects

A R Brito

Publications and source records attributed to A R Brito.

9 recordsLinked to original sources

PubMed2000

Evaluation of the gastroprotective activity of cordatin, a diterpene isolated from Aparisthmium cordatum (Euphorbiaceae).

Aparisthmium cordatum (Juss.) BAIL. (Euphorbiaceae) is a medium sized tree native to the North Brazilian coastal region, which is known in the State of Pará as "ariquena queimosa." To our knowledge it has no popular use. Phytochemical studies of the benzene extract of the bark of A. cordatum yielded a furan diterpene with a clerodane skeleton, called cordatin. Recently, we reported the antiulcerogenic activity of trans-dehydrocrotonin (DHC), another furan diterpene isolated from Croton cajucara bark, in different ulcerogenic models in mice and rats. The aim of the present study was to assess the possible antiulcerogenic activity of cordatin, another compound of the clerodane diterpene group present in A. cordatum bark. When previously administered (p.o.) at the dose of 100 mg/kg, cordatin significantly reduced (p<0.01) gastric injury induced by the indomethacin/bethanechol (78%), ethanol (76%), and hypothermic restraint-stress models (66%) and by pylorus ligature (50%) in mice and rats. In the HCl/ethanol-induced gastric ulcer model in mice, at oral doses of 100 and 250 mg/kg, cordatin from A. cordatum significantly reduced (p<0.001) the formation of gastric lesions by 70% and 77%, respectively, when compared to the control. In the pylorus-ligature model, cordatin (p.o.) only decreased the volume of gastric juice compared to the control (p<0.001). When cordatin (100 mg/kg) was administered intraduodenally to mice, significant modifications were found, such as a decrease in gastric acidity compared to the control (p<0.05). In the animals pre-treated with cordatin, free mucus production was not altered when compared with the control group. The results suggest that cordatin from A. cordatum presents a significant anti-ulcer effect when assessed in these induced ulcer models. Although the mechanism underlying this antiulcerogenic effect remains unknown, it seems to be related to an anti-secretory property but the involvement of mucosal defensive mechanisms are not to be ignored. The good yield of cordatin obtained from A. cordatum, as well as its antiulcerogenic activity, suggest that this compound should be submitted to pharmacological research as a potential new antiulcerogenic drug.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed1999

Antiulcerogenic mechanisms of dehydrocrotonin, a diterpene lactone obtained from Croton cajucara.

The bark of Croton cajucara Benth, is used in Brazilian folk medicine as an infusion to treat gastrointestinal disorders. The aim of the present study was to assess the mechanisms involved in the antiulcerogenic activity of dehydrocrotonin (DHC), a diterpene isolated from C. cajucara bark. We studied the effects of DHC on pylorus ligature (Shay) in mice treated with the drug (100 mg/kg) by the intraduodenal route. DHC did not induce any alteration in gastric volume in Shay mice but modified the pH and total acid concentration of gastric juice. Incubation of gastric juice with DHC did not reduce gastric acidity compared to control. We also investigated the effects of DHC on the response to histamine of right atria isolated from guinea pigs and on the response to carbachol of stomach fundus strips from rats. The concentration-response curves for the chronotropic effect of histamine in guinea pig right atria were shifted to the right, with a significant decrease in the maximum response, in the presence of DHC. Similar results were obtained with DHC (30 microM) for the concentration-response curves to carbachol in the isolated rat stomach. The ability of DHC to increase PGE2 release from rat stomach mucous cells was also studied. We observed that DHC induced a significant increase in PGE2 production (60% compared to control). In addition, the effects of DHC on the healing of acetic acid-induced gastric ulcer in rats were evaluated 14 days after acid injection. Oral administration of DHC (100 mg/kg per day) for 14 consecutive days had no effect on gastric ulcer healing in rats. Thus, the protective effect of DHC on induced gastric lesions could be due to synergistic effects, e.g., an increase in PGE2 release and non-competitive antagonism of H2-receptors and of muscarinic receptors. Whereas the former result represents an increase in the protective factors, the latter one shows a decrease in the aggressive factors against the gastric mucosa.

Animals↗

PubMed1999

Anti-inflammatory and antinociceptive effects in rodents of the essential oil of Croton cajucara Benth.

The plant Croton cajucara Benth. (Euphorbiaceae) is widely used in Amazonian folk medicine for the treatment of a wide range of illnesses. In this investigation the analgesic and anti-inflammatory properties of the essential oil from the bark of C. cajucara Benth., administered orally, were determined in several standard rodent models of pain and inflammation. We observed that pretreatment with essential oil significantly reduced the latency of sleeping time evoked by pentobarbital compared with the control group (P < 0.001). Doses of 100 or 1000 mg kg(-1) also increased the sleeping time induced by pentobarbital (30.9 +/- 3.91 and 52.1 +/- 15.6 min, respectively) compared with the negative control (12.4 +/- 4.27 min). We investigated the antinociceptive effect of the essential oil in chemical (acetic acid) and thermal (hot-plate) models of nociception in mice. Dipyrone (200 mg kg(-1)) and the highest doses of the essential oil (1000 mg kg(-1)) significantly inhibited acetic acid-induced abdominal constriction in mice (5.00 +/- 1.38 and 6.8 +/- 2.1 constrictions, respectively) compared with the negative control (33.1 +/- 2). The same dose of essential oil also raised the pain thresholds of mice in the hot-plate test and significantly (P < 0.05) increased the latency at all observation times. In acetic acid-induced abdominal constriction in mice pretreatment of the animals with naloxone (5 mg kg(-1)) significantly reversed the analgesic effect of morphine and of the essential oil at the highest dose (1000 mg kg(-1)). The essential oil of C. cajucara was also investigated for its anti-inflammatory properties. At the lowest dose (100 mg kg(-1)) the essential oil had anti-inflammatory effects in animal models of acute (carrageenin-induced paw oedema in mice) and chronic (cotton pellet granuloma) inflammation. The essential oil at doses of 50, 100 and 200 mg kg(-1) significantly and dose-dependently inhibited carrageenan-induced oedema (49 +/- 5; 37 +/- 5; 34 +/- 8 mg, respectively) compared with the negative control (74 +/- 8 mg). The essential oil (100 mg kg(-1)) also inhibited chronic inflammation by 38% whereas diclofenac inhibited it by 36%. However, the essential oil did not inhibit the migration of neutrophils into the peritoneal cavity. These data show that the essential oil from C. cajucara contains compounds that had a significant antinociceptive effect when the oil was administered at the highest dose. This effect seems to be related to interaction with the opioid system. The essential oil also had a significant anti-inflammatory effect in acute and chronic inflammation models when administered at lower doses. This effect seems to be related to cyclooxygenase inhibition.

Analgesics, Opioid↗

PubMed1998

Antiulcerogenic activity of trans-dehydrocrotonin from Croton cajucara.

trans-Dehydrocrotonin (DHC), the major diterpene isolated from Croton cajucara Benth, was assayed for antiulcerogenic activity in four induced gastric ulcer models in the rat. At an oral dose of 100 mg/kg DHC showed a significant antiulcerogenic effect on ulcers induced by hypothermic restraint stress, ethanol, and pylorus ligature. No significant changes in indomethacin-induced gastric lesions or modifications in gastric parameters such as wall mucus, secretion rate, pH, and total acid content were found after DHC treatment. The acute toxicological effects of DHC were assessed in mice. The LD50 values were 876 mg/kg and 47.2 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of DHC was also studied. A dose-dependent inhibition of cell viability was observed in V-79 fibroblast cell cultures with an IC50 of 240 microM. The high yields of DHC obtained from dried C. cajucara barks as well as its good antiulcerogenic activity and low toxicity support the pharmacological study of this compound as a potential new antiulcerogenic drug.

Animals↗

PubMed1996

How to study the pharmacology of medicinal plants in underdeveloped countries.

This paper presents a reflection based on 15 years' experience of studies on the pharmacology of medicinal plants in an underdeveloped country, Brazil. In these countries the investment in research is small and frequently interrupted. There is no new-medicines development program. Brazilian pharmaceutical companies have been short-sighted and have not developed new drugs. Although the diversity of the Brazilian flora is a remarkable opportunity for the development of new medicine products, natural product research is limited to a small group. These difficulties are common to all underdeveloped countries. Strategies for the pharmacological study of medicinal plants are proposed, the main difficulties are identified and a discussion of possible ways to overcome them is presented.

Animals↗

PubMed1993

Forty years of Brazilian medicinal plant research.

The Brazilian Foundation of Medicinal Plants has developed a medicinal plant database. Data were obtained from communications presented in Brazilian Scientific Meetings in the 1949-1989 period and include plant species, family, local name, part used, extract analyzed, claimed therapeutic action, pharmacological activity and active compounds. The families most frequently studied and the usual popular indications are analyzed. The history of research during this period and the current state of medicinal plant research in Brazil are outlined.

Brazil↗

PubMed1990

A double perfusion system with two-channel recording for the simultaneous study of the contractile responses of the circular and longitudinal smooth muscle layers of the rat vas deferens.

A device for double perfusion of the vas deferens externally and through the lumen is described in detail. The perfusion system allows the simultaneous recording of drug-induced or spontaneous contractions of the circular and longitudinal smooth muscle layers of the organ. Isometric contractions of the longitudinal (external) layer are recorded through a tension transducer. The contractions of the circular (internal) smooth muscle layer are recorded as changes of the pressure of internal perfusion. Therefore, four different effects can be recorded for a given concentration of agonist by combining the variables related to the route of perfusion (external or internal) and type of muscle (longitudinal or circular). In addition, antagonism or synergism can be studied by simultaneously perfusing a second drug. Results can be expressed as single records or as mean concentration-response curves from which drug-receptor parameters can be directly or indirectly obtained. The importance of employing this method for the analysis of some less usual problems related to the mechanism of drug action is discussed.

Animals↗

PubMed1989

Do differences in innervation result in different post-synaptic responses to exogenous agonists?

1. The pharmacological reactivity of the epididymal and prostatic portions of the rat vas deferens to BaCl2, phenylephrine and carbachol were recorded by isometric and isotonic technique. 2. The maximum response induced by the three agonists were similar at the epidiymal end, while at the prostatic portion phenylephrine produced a response 80% lower than that of barium and carbachol. 3. The pD2 value to agonists and the sensitivity to calcium channel blockers were lower at the prostatic end. 4. The data suggest that not only the pharmacological reactivity of the prostatic and epididymal portions differs, but also that the activity of the prostatic portion is much more reduced to alpha 1-agonists.

Animals↗

PubMed1988

Some pharmacological properties of the circular smooth muscle layer of the rat vas deferens.

Vas deferens preparations were perfused in-vitro through the lumen and externally with a modified Tyrode solution alone or containing drugs. Contractions of the circular (internal) smooth muscle layer were recorded as changes in the pressure of internal perfusion. Contractions of the longitudinal (external) layer were simultaneously recorded through a tension transducer. When the organ was perfused through the lumen, the circular layer contracted after addition of methacholine (pD2 = 4.13), and noradrenaline (pD2 = 5.00), and relaxed after addition of isoprenaline (pD2 = 5.22). These effects were also observed when the drugs were perfused externally, although with lower values of pD2 for noradrenaline and methacholine. The circular fibres were less sensitive when compared with the longitudinal fibres perfused externally with the above agonists. Methacholine-induced contractions of the circular layer were competitively antagonized by atropine (pA2 = 8.53), indicating the presence of muscarinic receptors. The effects induced by noradrenaline and isoprenaline were antagonized by indoramin (pA2 = 7.78), and timolol (pA2 = 8.68), respectively, indicating the presence of alpha- and beta-adrenoceptors. The effect of noradrenaline was potentiated by cocaine and denervation, indicating the presence of neuronal uptake, and by corticosterone, indicating the presence of extraneuronal uptake in the circular layer.

Animals↗