Effect Of Lysine Acetylsalicylate Research Articles

Effect of lysine acetylsalicylate on aluminium accumulation and (Na+/K+)ATPase activity in rat brain cortex synaptosomes after aluminium ingestion

Aluminium is neurotoxic in humans and has been implicated in several neurological disorders. Chronic use of buffered aspirins, as aspegic, would likely constitute the major human aluminium uptake source. Low-dose aspirin is beneficial in secondary prevention of cardiovascular events, so it is widely used for long periods of time. We studied if oral administration of aspegic to rats modified the aluminium inhibitory effect on brain (Na+/K+)ATPase due to alteration in synaptosomal membrane aluminium content. Adult male Wistar rats were submitted to sub-acute (1.00g/day during 10 days) and chronic (0.03g/day during 4 months) dietary AlCl3 exposure and/or to aspegic (0.11g/day). The exposure protocol increased the synaptosomal aluminium content especially after a long-term exposure to aluminium and aspegic. Although no alterations were observed in rat body weight gain and adenylate energy charge, the (Na+/K+)ATPase activity was significantly reduced when aluminium was orally administered to rats. The oral administration of aspegic increased the synaptosomal aluminium content and concomitantly enhanced the (Na+/K+)ATPase inhibition. In our exposure protocol the increase in synaptosomal aluminium content correlates with the reduction of the (Na+/K+)ATPase activity.

Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury

The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg−1 of PQ and 125 mg kg−1 of PQ + 316 mg kg−1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury.

Lysine acetylsalicylate improves the safety of paraquat formulation in rats by increasing its elimination and preventing lung and kidney injury

The incorporation of lysine acetylsalicylate (LAS) in the commercial formulation of paraquat (PQ), Gramoxone®, has been shown to significantly increase the survival of intoxicated mammals while maintaining the herbicidal effect. The aim of the present study was to clarify the mechanisms involved in the protective effect of LAS in a rodent model through monitoring PQ levels and the histological and biochemical biomarkers of toxicity in male Wistar rats following intoxication with PQ formulations in the absence and presence of LAS. Gramoxone® and the formulation with LAS were administered by gavage at the doses of 125 mg kg−1 of PQ and 125 mg kg−1 of PQ + 316 mg kg−1 of LAS, respectively. The obtained results showed that LAS improves the safety of PQ formulation by increasing its elimination and preventing lung and kidney injury. LAS prevented the biochemical and histological alterations in lung induced by PQ measured at the end of 24 h and 48 h. This was evidenced by a significant reduction in lipid peroxidation, the maintenance of reduced glutathione levels and decreased levels of oxidized glutathione, as well as the normalization of the urinary biomarkers, creatinine and N-acetyl-β-glucosaminidase. LAS treatment also caused a significant reduction in PQ-induced activation of nuclear factor kappa B (NF-κB) in the lung. The results allow us to conclude that lysine acetylsalicylate improves the safety of PQ formulation in rats by increasing its elimination and preventing lung and kidney injury.

The Effect of Lysine Acetylsalicylate on Somatostatin Inhibition of Insulin Secretion Induced by Arginine

The inhibitory effect of somatostatin (SRIF) on immunoreactive insulin release and on many other hormonal secretions has been widely studied in both animal and man. However, the mechanism by which SRIF acts on these functions remains poorly defined. Aim of this study is to determine the inhibitory effect of SRIF on insulin secretion induced by arginine after the administration of lysine acetylsalicylate (LAS) in a dose which inhibits the endogenous synthesis of prostaglandins. Ten healthy informed volunteer subjects were studied. Four studies were carried out in randomized order, each one separated by a three day interval. The first study was a test of arginine (25 g i.v. in 30 min). The second study was a test of arginine with SRIF infusion (150 micrograms bolus followed by 100 micrograms/h for 120 min). The third study was a test of arginine with an infusion of SRIF and LAS (66 mg/min for 120 min). The fourth study was a test of arginine with LAS infusion. Plasma insulin levels were determined by radioimmunoassay. After arginine administration the typical biphasic insulin response was observed with a precocious peak at 3 min and a late peak at 30 min. This response is not significantly modified under LAS infusion. With the infusion of SRIF at a dose of 100 micrograms/hr after arginine administration only a very modest insulin response was observed. The addition of LAS does not modify the inhibitory effect of SRIF on insulin secretion induced by arginine. This result demonstrates that the inhibitory action of SRIF on the secretion of insulin is not dependent upon the activation of the endocellular prostaglandin system.

The effect of lysine acetylsalicylate on joint capsule mechanoreceptors in rats with polyarthritis.

Joint capsule mechanoreceptors in arthritic rats are more sensitive to pressure than similar receptors in normal animals. This greater sensitivity was reversed by the intravenous or topical administration of lysine acetylsalicylate in anaesthetised rats in doses of 15 to 50 mgm ASA-equivalent/kg. The reduction in sensitivity began within 5-10 min and reached a minimum mean value of 35% of the control after 35 to 40 min. During this period there was a negative linear or exponential relation between the amplitude of response to a controlled mechanical stimulus and time after administration of lysine acetylsalicylate. Control values of sensitivity were reached about 65-70 min following treatment with lysine acetylsalicylate. The results are interpreted as indicating that the high sensitivity of the arthritic joint capsule receptors is due to locally produced prostaglandins, such as prostacyclin.

Renal Hemodynamic Abnormalities in Patients with Short Term Insulin-Dependent Diabetes Mellitus: Role of Renal Prostaglandins*

To determine if renal functional alterations in diabetes mellitus could be related to disturbances of vasoactive systems, renal plasma flow (RPF), glomerular filtration rate (GFR), PRA (basal and stimulated), plasma catecholamine levels, and urinary excretion of prostaglandin E2 (PGE2), 6-keto-PGF1 alpha, and kallikrein were determined in 21 patients with insulin-dependent diabetes mellitus (IDDM) of short duration and 15 normal subjects. In 7 additional patients with IDDM and in 4 normal subjects, the effect of lysine acetylsalicylate (LAS; 450 mg, iv) on GFR and RPF was studied. Patients with IDDM had higher RPF and GFR than normal subjects. Plasma norepinephrine and basal and stimulated PRA were significantly lower in IDDM than in the control group [161 +/- 82 (+/- SD) vs. 243 +/- 114 pg/ml, 0.19 +/- 0.20 vs. 1.15 +/- 0.33 ng/ml X h, and 0.93 +/- 0.82 vs. 2.8 +/- 1.73 ng/ml X h, respectively). No significant differences were found in the urinary excretion of PGE2, 6-keto-PGF1 alpha, and kallikrein in the two groups. LAS administration significantly reduced RPF (from 641 +/- 72 to 535 +/- 38 ml/min X 1.73 m2) and GFR (from 168 +/- 25 to 150 +/- 18 ml/min X 1.73 m2) in patients with IDDM, but not in normal subjects. In IDDM patients, there was a close direct correlation between the percent decrease in RPF and GFR induced by LAS and the baseline values of these parameters. The results suggest that in IDDM, there may be an imbalance between the degree of activation of the renin-angiotensin and sympathetic nervous systems and the renal production of PGs. The observation that LAS administration reduced RPF and GFR in these patients suggests that renal PGs are involved in the renal hyperperfusion of IDDM.

Effect of lysine acetylsalicylate on biliary lipid secretion in dogs.

1. The influence of lysine acetylsalicylate on bile flow, erythritol clearance and bile salt, phospholipid and cholesterol secretion in bile was studied in unanaesthetized dogs fitted with a Thomas duodenal cannula. 2. Lysine acetylsalicylate induced a marked increase in bile flow and a parallel increase in erythritol clearance although the bile salt secretion remained unchanged; this suggests that the compound stimulated the formation of the canalicular (hepatocytic) bile salt-independent fraction of bile flow. 3. Lysine acetylsalicylate induced a significant decrease in biliary phospholipid and cholesterol secretion and the cholesterol saturation of bile was significantly reduced. 4. It is postulated that the decrease in phospholipid and cholesterol secretion resulted from the dilution of intracanalicular bile salts. This effect of lysine acetylsalicylate, and possibly of other bile salt-independent choleretics, may be of value in the treatment of cholesterol gallstones in man.