Protective role of gamma-aminobutyric acid against chronic renal failure in rats.
The protective effect of gamma-aminobutyric acid (GABA) against chronic renal failure (CRF) was investigated using a remnant kidney model with 5/6 nephrectomized rats. Nephrectomy led to renal dysfunction, which was evaluated via several parameters including serum urea nitrogen, creatinine (Cr) and Cr clearance. However, the administration of GABA ameliorated renal dysfunction, and a longer administration period of GABA increased its protective effect. In addition, nephrectomized control rats showed an elevation in the fractional excretion of sodium (FE(Na)) with an increase in urinary sodium, while GABA led to a significant decline in FE(Na). Moreover, nephrectomy resulted in a decrease of serum albumin and an increase of urinary protein with a change in the urinary protein pattern, whereas the rats administered GABA showed improvement in these changes associated with CRF caused by nephrectomy. This suggests that GABA would inhibit the disease progression and have a protective role against CRF. As one of the risk factors for CRF progression, hypertension was also regulated by GABA. The results also indicate that GABA may play a protective role against CRF through improvement of the serum lipid profile, with reductions in triglyceride and total cholesterol. Furthermore, nephrectomy led to renal oxidative stress with a decrease in the activity of antioxidative enzymes and elevation of lipid peroxidation. The administration of GABA attenuated oxidative stress induced by nephrectomy through an increase in superoxide dismutase and catalase, and decrease in lipid peroxidation. The histopathological lesions, including glomerular, tubular and interstitial lesions, under nephrectomy were also improved by GABA with the inhibition of fibronectin expression. This study demonstrated that GABA attenuated renal dysfunction via regulation of blood pressure and lipid profile, and it also ameliorated the oxidative stress induced by nephrectomy, suggesting the promising potential of GABA in protecting against renal failure progression.
Sasaki
Sumiyo
S
Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama, Japan.
Yokozawa
Takako
T
Cho
Eun Ju
EJ
Oowada
Shigeru
S
Kim
Mujo
M
D000284:Administration, Oral; D000419:Albuminuria / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006937:Hypercholesterolemia / Q000209:etiology / Q000517:prevention & control; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D009392:Nephrectomy / Q000009:adverse effects / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014554:Urination / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D000975:Antioxidants; D000960:Hypolipidemic Agents; D017392:Thiobarbituric Acid Reactive Substances; D005680:gamma-Aminobutyric Acid; D012964:Sodium; D003404:Creatinine; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase