title: Therapeutic efficacy of lipoic acid in combination with dimercaptosuccinic acid against lead-induced renal tubular defects and on isolated brush-border enzyme activities.
abstract: The combined therapeutic potentials of lipoic acid and dimercaptosuccinic acid were compared against their sole administrations in restoring the altered lead sensitive indices in urine and isolated renal brush-border preparations. Toxicity was induced in male albino rats (Wistar strain) by administering lead acetate (0.2%) in drinking water for 5 weeks, followed by therapy comprising lipoic acid (25 mg/kg body weight) and dimercaptosuccinic acid (20 mg/kg body weight) solely as well as combined during the 6th week. Changes in kidney weights encountered upon lead administration improved after therapy with lipoic acid and dimercaptosuccinic acid. Renal integrity was assessed by measuring the activities of alkaline phosphatase, acid phosphatase, lactate dehydrogenase, leucine aminopeptidase, N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transferase and beta-glucuronidase in urine along with some urinary constituents (urea, uric acid, creatinine, protein and phosphorous). The effects of lead were also studied on isolated brush-border enzymes (alkaline phosphatase, acid phosphatase, gamma-glutamyl transferase and beta-glucuronidase) that showed a decline upon its administration. Increased activities of urinary enzymes were accompanied by increase in the urinary constituents. Increase in renal lead content was paralleled by a drastic fall in the renal delta-aminolevulinic acid dehydratase and a rise in urinary lead levels. Relative to the administration of lead, the combined therapy showed betterment on the renal integrity with respect to the functional parameters assessed, thereby indicating its efficacy over the monotherapies.
authors.affiliation: Department of Medical Biochemistry, Dr. A.L.M. PGIBMS, University of Madras, Taramani Campus, Chennai 600113, India. prasadrsp@rediffmail.com
authors.forename: Thylambal Rajagopalan
authors.initials: TR
authors.lastname: Sivaprasad
authors.forename: Saroja Palanichamy
authors.initials: SP
authors.lastname: Malarkodi
authors.forename: Palaninathan
authors.initials: P
authors.lastname: Varalakshmi
mesh_terms: D000624:5-Aminolevulinate Synthetase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D015415:Biomarkers / Q000652:urine; D001835:Body Weight / Q000187:drug effects; D002614:Chelating Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology; D007855:Lead Poisoning / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000652:urine; D008297:Male; D008871:Microvilli / Q000187:drug effects* / Q000201:enzymology; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000633:toxicity / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D004113:Succimer / Q000627:therapeutic use*; D008063:Thioctic Acid / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D002614:Chelating Agents; D009942:Organometallic Compounds; D008063:Thioctic Acid; D004113:Succimer; D000624:5-Aminolevulinate Synthetase; C008261:lead acetate