Anthony Josephine

Evaluating the effect of sulphated polysaccharides on cyclosporine a induced oxidative renal injury.

Cyclosporine A (CsA) has been universally used as an immunosuppressant for the management of organ transplantation and various autoimmune diseases. However, nephrotoxicity due to CsA remains to be an important clinical challenge. In the present investigation, an attempt has been made to appraise the effect of sulphated polysaccharides on oxidative renal injury caused by CsA. Adult male Wistar rats were divided into four groups. Two groups received CsA by oral gavage (25 mg/kg body weight) for 21 days to provoke nephrotoxicity, one of which simultaneously received sulphated polysaccharides subcutaneously, (5 mg/kg body weight). A vehicle (olive oil) treated control group and sulphated polysaccharides drug control were also built-in. An increase in lipid peroxidation along with abnormal levels of enzymic (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glucose-6-phosphate dehydrogenase) and non-enzymic antioxidants (glutathione, vitamin C and vitamin E) are the salient features observed in CsA induced nephrotoxicity. CsA induced impairment of renal toxicity was evident from the marked decline in the activities of renal marker enzymes like alkaline phosphatase, acid phosphatase and lactate dehydrogenase, as well as an apparent increase in the serum urea, uric acid and creatinine; diagnostic of renal damage was normalized by sulphated polysaccharides co-administration. Sulphated polysaccharides treatment showed an effectual role in counteracting the free radical toxicity by bringing about a significant decrease in peroxidative levels and increase in antioxidant status. These observations emphasize the antioxidant property of sulphated polysaccharides and its cytoprotective action against CsA induced nephrotoxicity.

Effect of sulphated polysaccharides on erythrocyte changes due to oxidative and nitrosative stress in experimental hyperoxaluria

Kidney stones are known to haunt humanity for centuries and increase in oxalate is a predominant risk factor for stone formation. The present study was initiated with a notion to study the oxidative and nitrosative stress on erythrocytes under oxalate stress and the putative role of sulphated polysaccharides. Hyperoxaluria was induced in two groups by the administration of 0.75% ethylene glycol in drinking water for 28 days and one of them was treated with sulphated polysaccharides from Fucus vesiculosus from the 8th day to the end of the experimental period of 28 days at a dose of 5 mg/kg body weight subcutaneously. Control and drug control (sulphated polysaccharides alone) were also included in the study. Glycolic and glyoxylic acid levels of urine were analyzed as an index of hyperoxaluria. The plasma enzymic markers of cellular integrity, redox status of red blood cells, osmotic fragility, and 14C-oxalate binding were investigated. Urine and plasma nitric oxide metabolites, expression of inducible nitric oxide synthase protein, and mRNA were assessed in kidney to evaluate the nitrosative stress. Increased levels of glycolic and glyoxylic acid in urine indicated the prevalence of hyperoxaluria in ethylene glycol–administered groups. Plasma aspartate and alanine transaminase were not altered, but alkaline phosphatase and lactate dehydrogenase of hyperoxaluric group were increased indicating tissue damage. Activities of antioxidant enzymes were decreased, whereas erythrocyte membrane lipid peroxidation was increased in hyperoxaluric rats. Moreover, an altered fragility with an increase in oxalate binding activity was observed in hyperoxaluric group. Increase in nitric oxide metabolites levels in urine and plasma along with an increase in expression of inducible nitric oxide synthase protein and mRNA in kidney were observed in hyperoxaluric rats. Administration of sulphated polysaccharides to hyperoxaluric rats averted the abnormal increase in urinary glycolic and glyoxylic acid levels and enzyme activities, decreased lipid peroxidation, and increased the activities of antioxidant enzymes. Furthermore, increased nitrosative stress accompanying hyperoxaluria was also normalized on sulphated polysaccharides treatment. To conclude, sulphated polysaccharide administration was able to maintain the integrity of erythrocyte membrane and decrease the damage to erythrocytes in hyperoxaluria.

Physico‐chemical alterations of urine in experimental hyperoxaluria: a biochemical approach with fucoidan

Urinary supersaturation‐induced crystal formation has been attributed as one of the key factor for the pathogenesis/progression of lithogenesis. This study was aimed at investigating whether fucoidan, a naturally occurring sulfated glycosaminoglycan, could ameliorate the biochemical changes in urine induced by stone formation. Two groups of male albino Wistar rats (120 ± 20 g) received 0.75% ethylene glycol (EG) for 28 days to induce hyperoxaluria, and one of them received sulfated polysaccharides (fucoidan from Fucus vesiculosus, 5 mg kg−1, S.C.), commencing from the 8thday of the experimental period. One group was maintained as normal control group and another group served as drug control, which received sulfated polysaccharides. The urine collected from all the groups was analysed for changes in pH, volume, oxalate, calcium, phosphorus, uric acid, magnesium, citric acid and glycosaminoglycans. Urinary crystals were analysed with a light microscope. Renal tissues were studied under polarized light for deposition of crystals and also analysed for their oxalate and calcium content. The changes in extracellular matrix on crystal deposition were also evaluated. The urinary pH and volume were altered in rats treated with EG along with an increase in weight of the kidney. Further, administration of EG to rats increased the supersaturation of urine by escalating the levels of the stone‐forming constituents, such as oxalate, calcium, phosphorus and uric acid, which was completely restored by fucoidan treatment. The decrease in the inhibitors, like citrate, magnesium and glycosaminoglycans, in urine was prevented by the co‐treatment with fucoidan. In hyperoxaluric rats, there was an increased excretion of calcium oxalate monohydrate crystals in urine along with crystal deposition in renal tissues; this was prevented by fucoidan treatment. Fucoidan administration reversed even the tissue levels of calcium and oxalate. The increased accumulation of collagen and expression of transforming growth factor‐β1 in hyperoxaluria was normalized on fucoidan administration. These results suggest that the physico‐chemical alterations in urine produced during hyperoxaluria can be reversed by fucoidan administration.