oxalates and lupeol

The present study was undertaken to explore the efficiency of the pentacyclic triterpene lupeol (1) and its ester derivative, lupeol linoleate (2), in experimental hyperoxaluria. Hyperoxaluria was induced in male Wistar rats with 0.75% ethylene glycol (EG) in drinking water for 28 days. Hyperoxaluric animals were supplemented orally with 1 and 2 (50 mg/kg body wt/day) throughout the experimental period of 28 days. The renal enzymes were assayed as markers of renal tissue integrity. The redox status and oxalate metabolism in animals under oxalate overloading was also assessed. Microscopic analysis was done to investigate the abnormalities associated with oxalate exposure in renal tissues. Increase in oxidative milieu in hyperoxaluria was evident by increased lipid peroxidation (LPO) and decreased enzymic and nonenzymic antioxidants. Decrease in the activities of renal enzymes exemplified the damage induced by oxalate, which correlated positively with increased LPO and increased oxalate synthesis. Renal microscopic analysis further emphasized the oxalate-induced damage. These abnormal biochemical and histological aberrations were attenuated with test compound treatment, with 2 more effective than 1. From the present study, it can be concluded that 1 and 2 may serve as candidates for alleviating oxalate toxicity.

Topics: Administration, Oral; Animals; Disease Models, Animal; Ethylene Glycol; Hyperoxaluria; Kidney Calculi; Lipid Peroxidation; Male; Oxalates; Pentacyclic Triterpenes; Rats; Rats, Wistar; Triterpenes; Urolithiasis

Investigations were carried out to evaluate the efficacy of the pentacyclic triterpene, lupeol and its ester, lupeol linoleate, against calcium oxalate urolithiasis in rats. Administration of a pyridoxine deficient diet containing 3% glycollic acid for 21 days led to increased excretion of stone forming constituents such as calcium, oxalate and uric acid. Crystal deposition and subsequent renal tubular damage resulted in increased excretion of the tubular enzymes alkaline phosphatase, lactate dehydrogenase, gamma glutamyl transferase, beta glucuronidase and N-acetyl glucosaminidase along with reduced fibrinolytic enzymes. A reduction in the urinary inhibitory factors magnesium and glycosaminoglycans was also observed. Treatment with lupeol and lupeol linoleate reduced the extent of tubular damage as evidenced from reduced enzymuria and minimized the excretion of stone forming constituents.

Topics: Acetylglucosaminidase; Alkaline Phosphatase; Animals; Calcium; Calcium Oxalate; gamma-Glutamyltransferase; Glucuronidase; Hyperoxaluria; L-Lactate Dehydrogenase; Male; Oxalates; Pentacyclic Triterpenes; Pyridoxine; Rats; Rats, Wistar; Risk Factors; Triterpenes; Uric Acid; Urinary Calculi

Naturally occurring pentacyclic triterpenes of plant origin have been identified as possessing a wide range of pharmacological effects. Lupeol (Lupa-21,20(29) dien, 3beta-ol) has been found to be efficient in reducing the risk of stone formation in animals by way of preventing crystal-induced tissue damage and dilution of urinary stone-forming constituents. In the present study, two structurally related triterpenes, lupeol and betulin (Lupa-20(29)ene-3,28 diol) were assessed for their antilithiatic effect. Foreign body implantation method followed by supplementation of ammonium oxalate was adapted to induce stone formation in the bladder. This led to elevated lipid peroxidation and depleted antioxidant status in the renal tissues. Both the triterpenes were equally efficient in minimizing crystal-induced renal peroxidative changes measured in terms of malondialdehyde and subsequent tissue damage. The antioxidant status, comprising of the enzymatic and non-enzymatic components, was found to be significantly depleted in the kidney and bladder of stone-forming animals. Both lupeol and betulin were comparable in their ability to restore the thiol status and the antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase. The mechanism by which the two compounds render protection against oxalate-induced toxic manifestations and free radical production may involve the inhibition of calcium oxalate crystal aggregation and enhancement of the body defence systems. 2000 Academic Press.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Catalase; Crystallization; Free Radicals; Glutathione; Glutathione Transferase; In Vitro Techniques; Lipid Peroxidation; Malondialdehyde; Oxalates; Pentacyclic Triterpenes; Plants, Medicinal; Rats; Thiobarbituric Acid Reactive Substances; Triterpenes; Urinary Bladder; Urinary Calculi

Investigations were carried out to evaluate the effect of two, structurally related, triterpenes-betulin and lupeol-on the membrane peroxidation and antioxidant systems in red blood cells, during pyridoxine-deficient condition in rats. Increased lipid peroxidation levels in the absence and presence of ferrous sulphate, an inducer of lipid peroxidation, indicated peroxidative damage to the red-cell membrane. Na(+), K(+)-ATPase activity was decreased while that of other ion-specific ATPases were increased in the red cells of pyridoxine-deficient rats. Antioxidants, such as reduced glutathione, glutathione peroxidase, catalase, glutathione reductase and glutathione S-transferase were decreased, while superoxide dismutase alone was increased in the pyridoxine-deficient rat red blood cells. The red-cell osmotic fragility was found to be reduced. Treatment with the triterpenes proved effective in restoring the normal condition.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Erythrocytes; Hyperoxaluria; Lipid Peroxidation; Male; Oxalates; Pentacyclic Triterpenes; Pyridoxine; Rats; Rats, Wistar; Triterpenes