title: Chitosan Prevents Gentamicin-Induced Nephrotoxicity via a Carbonyl Stress-Dependent Pathway.
abstract: Aminoglycosides are widely used to treat infections; however, their applications are limited by nephrotoxicity. With the increase of antibiotic resistance, the use of aminoglycosides is inevitable. Low-molecular-weight chitosan (LMWC) has shown renal protective effects in dialysis patients. However, no study has evaluated LMWC for preventing aminoglycoside-induced nephrotoxicity or determined the mechanisms underlying the renal protective effects. In this study, LMWC (165 or 825 mg/kg/day) or metformin (100 mg/kg/day) was orally administered for 13 days to rats with nephropathy induced by gentamicin (GM), a kind of aminoglycoside (150 mg/kg/day i.p. for 6 days). Both LMCW doses improved renal function. Serum creatinine levels improved in rats treated with 165 and 825 mg/kg/day LMWC (from 2.14 ± 0.74 mg/dL to 1.26 ± 0.46 mg/dL and 0.69 ± 0.12 mg/dL, resp., P < 0.05). Blood urea nitrogen levels were also improved in these rats (from 73.73 ± 21.13 mg/dL to 58.70 ± 22.71 mg/dL and 28.82 ± 3.84 mg/dL, resp., P < 0.05). Additionally, renal tissue morphology improved after LMWC treatment, and accumulation of renal methylglyoxal, a damage factor associated with carbonyl stress, was reversed. These results show that LMWC prevents GM-induced renal toxicity via a carbonyl stress-dependent pathway.
authors.forename: Chu-Kuang
authors.initials: CK
authors.lastname: Chou
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City 11031, Taiwan.
authors.forename: Yi-Chieh
authors.initials: YC
authors.lastname: Li
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City 11031, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Chen
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City 11031, Taiwan.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Shih
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wuxing Street, Taipei City 11031, Taiwan.
authors.forename: Jen-Ai
authors.initials: JA
authors.lastname: Lee
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D048271:Chitosan / Q000008:administration & dosage*; D005839:Gentamicins / Q000009:adverse effects; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008687:Metformin / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects*; D011765:Pyruvaldehyde / Q000097:blood; D051381:Rats; D006435:Renal Dialysis
chemical_list: D005839:Gentamicins; D011765:Pyruvaldehyde; D048271:Chitosan; D008687:Metformin