Protective role of sulphated polysaccharides in abating the hyperlipidemic nephropathy provoked by cyclosporine A.

Abstract

Cyclosporine A (CsA)-induced nephrotoxicity hampers the immense therapeutic potential of such a powerful immunosuppressant. The present study was conducted with an aim to explicate the contribution of sulphated polysaccharides (SPS) in abating the lipid abnormalities induced by CsA in the rat kidney. Hyperlipidemia associated with nephrotic syndrome may play a role in the worsening of renal function. Male albino Wistar rats sorted into four groups were used for the study. CsA was given at a dose of 25 mg/kg body weight, orally for 21 days. Significant alterations in the lipid profile as well an increase in the activity of cholesterol ester synthase, coupled with a decrease in cholesterol ester hydrolase and lipoprotein lipase enzyme activities were noted in the plasma and kidneys of CsA-administered rats. A marked increase in the lipoprotein fractions, low-density lipoprotein (LDL) and very low density lipoprotein (VLDL), along with a decrease in the HDL level were found in CsA-administered rats. The degree of nephrotoxicity allied with lipid discrepancies was evident from augmented urinary excretion of urea, uric acid and creatinine. Further, an enhanced susceptibility of the apo B-containing lipoproteins (LDL + VLDL) to oxidation in vitro, induced by copper ions was also found in the plasma of CsA given groups. While SPS co-treated groups (5 mg/kg body weight, subcutaneously) revealed a normalized lipid profile and lipid metabolizing enzymes, the supplementation of SPS also brought back the elevated urinary constituents close to that of the controls and substantially minimized the oxidative changes. With these observations, it may be concluded herein that SPS may be an ideal choice as a renoprotective and hypolipidemic agent against CsA-induced hyperlipidemic nephropathy.

• Authors: Anthony Josephine, Coothan Kandaswamy Veena, Ganapathy Amudha, Sreenivasan P Preetha, Palaninathan Varalakshmi
• Journal: Archives of toxicology (Arch Toxicol) Vol. 81 Issue 5 Pg. 371-9 (May 2007) ISSN: 0340-5761 [Print] Germany
• PMID: 17019561 (Publication Type: Journal Article)

Chemical References

• Cholesterol, LDL
• Cholesterol, VLDL
• Hypolipidemic Agents
• Immunosuppressive Agents
• Lipoproteins
• Polysaccharides
• Sulfates
• Uric Acid
• Malondialdehyde
• Cyclosporine
• Creatinine
• Phosphatidylcholine-Sterol O-Acyltransferase
• acid cholesterol ester synthetase
• Sterol Esterase
• Lipoprotein Lipase

Topics

• Animals
• Cholesterol, LDL (blood)
• Cholesterol, VLDL (blood)
• Creatinine (urine)
• Cyclosporine (toxicity)
• Hyperlipidemias (chemically induced, drug therapy)
• Hypolipidemic Agents (chemistry, isolation & purification, therapeutic use)
• Immunosuppressive Agents (toxicity)
• Kidney (drug effects, metabolism, pathology)
• Lipid Metabolism (drug effects)
• Lipoprotein Lipase (metabolism)
• Lipoproteins (metabolism)
• Male
• Malondialdehyde (metabolism)
• Nephrotic Syndrome (chemically induced, drug therapy)
• Phosphatidylcholine-Sterol O-Acyltransferase (metabolism)
• Polysaccharides (chemistry, isolation & purification, therapeutic use)
• Rats
• Rats, Wistar
• Sargassum (chemistry)
• Sterol Esterase (metabolism)
• Sulfates (chemistry)
• Uric Acid (urine)