Gastroprotective and cicatrizing activity of the Ziziphus joazeiro Mart. leaf hydroalcoholic extract.

Ziziphus joazeiro Mart., popularly known as 'juazeiro', is a species used in popular medicine for the treatment of bronchitis, gastric ulcers, skin wounds, and in the manufacture of cosmetic and food products. The objective of this study is to evaluate the gastroprotective and cicatrizing activity of the Z. joazeiro Mart. leaf hydroalcoholic extract (EHFZJ). The acute pre-clinical toxicity was determined by the single administration of the EHFZJ (2000 mg/kg/p.o.) and by assessing clinical signs of toxicity, according to established criteria by Malone, or mortality. Gastroprotective activity was identified through classical models of acute gastric lesions induced by indomethacin, absolute and acidified ethanol (100, 200 and 400 mg/kg/per os) and the physical barrier mechanism (400 mg/kg/per os or intraperitoneally). The cicatrizing activity of the EHFZJ was investigated by measuring the speed of wound closure and the percentage of contraction. The acute pre-clinical toxicity of EHFZJ showed no signs of toxicity and mortality. The EHFZJ demonstrated a gastroprotective effect at the 400 mg/kg dose in the classical models of acute gastric injury induced by indomethacin, absolute and acidified ethanol. The EHFZJ administration (orally) demonstrated significant inhibition, suggesting a possible physical barrier mechanism exists. The EHFZJ showed no significant differences in terms of percentage of contraction or the speed of wound closure during the observation times (0, 3, 7, 11 and 14 days). The results obtained in this study provide evidence of a potential gastroprotective activity for the Ziziphus joazeiro Mart. Leaf hydroalcoholic extract.

Chemical Analysis and Study of Phenolics, Antioxidant Activity, and Antibacterial Effect of the Wood and Bark of Maclura tinctoria (L.) D. Don ex Steud.

Maclura tinctoria (L.) D. Don ex Steud. has one of the highest qualities among the coefficients for Brazilian woods (up to 9.6) and resistance rates equivalent to Indian teak (Tectona grandis). In this study, the macromolecular constituents and total phenols compounds as well as the antioxidant and antibacterial activities of this wood were evaluated. Total phenols and proanthocyanidin levels were higher in wood when compared with bark levels. The antioxidant activity of wood extracts (IC(50) = 18.7 µg/mL) was more effective than that of bark extracts (IC(50) = 20.9 µg/mL). Wood and bark extracts revealed a high potential for inhibition of aerobic and anaerobic bacteria. The bark extracts were the most active (MIC from 20 to 60 µg/mL). Both antioxidant activity and high potential for bacteria inhibition turn these extracts promising for drug formulations, especially as antibacterial agent.

Effects of the nonsteroidal anti-inflammatory drug nimesulide on energy metabolism in livers from adjuvant-induced arthritic rats.

The effects of nimesulide on energy metabolism and the hepatic metabolic alterations produced by adjuvant-induced arthritis were investigated in the perfused rat liver an in isolated liver mitochondria. Nimesulide, at therapeutic levels (20-50 microM), produced: (1) stimulation of oxygen consumption in the perfused rat liver and in isolated mitochondria, (2) inhibition of gluconeogenesis; (3) reduction of ADP/O ratio and the respiratory control ratio and stimulation of glycogenolysis in the livers from healthy rats, but not in livers from arthritic rats. These results indicate that nimesulide acts as a mitochondrial uncoupler. The main alterations produced by adjuvant-induced arthritis were: higher rates of oxygen consumption in both perfused livers and isolated mitochondria, with no decrease in the efficiency of mitochondrial energy transduction; (2) decreased gluconeogenesis and lack of glycogenolytic response to uncouplers, but not to alpha 1-agonists. These data allow to conclude that nimesulide-induced impairment of energy metabolism should worsen the hepatic disturbances that are already associated with the adjuvant disease.

Metabolic effects of oxalate in the perfused rat liver.

The effects of oxalate on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if oxalate is also active in intact organs as demonstrated in isolated cells. The results revealed that the action of oxalate in the perfused liver resembles only partially that observed in isolated hepatocytes. In the perfused liver, oxalate inhibited gluconeogenesis from alanine, pyruvate and lactate, inhibited glycolysis and stimulated glycogenolysis. These observations confirm previous measurements with isolated hepatocytes. However, additional effects, not observed in isolated hepatocytes, were found. In the perfused liver, oxalate stimulated glucose production from dihydroxyacetone, glycerol or sorbitol. Moreover, the effects of oxalate in the perfused rat liver occurred at concentrations well above those reported for isolated hepatocytes, revealing that the compound is less toxic in the intact tissue. In vivo, the metabolic effects reported here can only be expected to occur at supra-physiological concentrations of oxalate, as in the case of a chronic renal failure.

Glycogenolysis stimulation by non-steroidal anti-inflammatories in the perfused rat liver is not accompanied by Ca2+ release.

Several non-steroidal anti-inflammatories increase glycogenolysis and are also able to affect intracellular Ca2+ channels. In the perfused liver, glycogenolysis stimulation is often associated with a transient Ca2+ efflux, which occurs immediately after the introduction of the glycogenolytic agonist. The purpose of this work was to verify if the introduction of non-steroidal anti-inflammatories also stimulates Ca2+ efflux. Rat livers were pre-loaded with 45Ca2+ in a recirculating system. The anti-inflammatory drugs diclofenac and niflumate were infused 10 minutes after restoration of the once-through perfusion. Glycogenolysis and oxygen uptake stimulation caused by these compounds was not accompanied by any increment in 45Ca2+ release. Subsequent infusion of vasopressin greatly stimulated 45Ca2+ efflux, denoting that the intracellular Ca2+ pools had not been depleted. These results corroborate previous results suggesting that Ca2+ is not involved in glycogenolysis stimulation caused by non-steroidal anti-inflammatories.

Effects of the nonsteroidal anti-inflammatory drug piroxicam on energy metabolism in the perfused rat liver.

1. The actions of piroxicam, a nonsteroidal and noncarboxylic anti-inflammatory drug, on the metabolism of the isolated perfused rat liver were investigated. The main purpose was to verify if piroxicam is also active on glycogenolysis and energy metabolism, as demonstrated for several carboxylic nonsteroidal anti-inflammatories. 2. Piroxicam increased oxygen consumption in livers from both fed and fasted rats. 3. Piroxicam increased glucose release and glycolysis from endogenous glycogen (glycogenolysis). 4. Gluconeogenesis from lactate plus pyruvate was inhibited. 5. The action of piroxicam on oxygen consumption was blocked by antimycin A, but not by atractyloside. 6. The action of piroxicam in the perfused rat liver metabolism seems to be a consequence of its action on mitochondria. 7. It can be concluded that inhibition of energy metabolism and stimulation of glycogenolysis are not specific properties of carboxylic nonsteroidal anti-inflammatory drugs.

Naproxen inhibits hepatic glycogenolysis induced by Ca(2+)-dependent agents.

1. The non-steroidal anti-inflammatory naproxen inhibited steady-state glycogenolysis stimulation caused by norepinephrine, phenylephrine (alpha 1-agonists) and methotrexate (not receptor mediated) in the isolated perfused rat liver. Stimulation of glycogenolysis caused by these agents is Ca(2+)-dependent. 2. Naproxen did not inhibit glycogenolysis stimulation caused by glucagon. 3. The action of naproxen depended on the extracellular Ca2+ concentration. At 0.25 mM extracellular Ca2+, the norepinephrine stimulated glycogenolysis was inhibited by 60% by 0.5 mM naproxen. At 3.5 mM Ca2+, inhibition was reduced to 25%. The inhibition degree correlated linearly with the extracellular Ca2+ concentration. 4. 45Ca2+ efflux stimulation caused by norepinephrine was not affected by naproxen, indicating that the mobilization of the intracellular Ca2+ pools was not significantly affected by naproxen. The initial increases in glycogenolysis caused by norepinephrine in the absence of extracellular Ca2+ (pre steady-state) were not affected by naproxen. These increases depend on intracellular Ca2+ mobilization. 5. It can be concluded that the action of naproxen is most probably related to the cytosolic Ca2+ concentration which, under steady-state conditions, depends on the extracellular one during the action of Ca(2+)-dependent glycogenolytic agents.