title: Renoprotective effects of gamma-aminobutyric acid on cisplatin-induced acute renal injury in rats.
abstract: To investigate the effect of gamma-aminobutyric acid (GABA) on acute renal injury (ARI), we used here a rat model of acute tubular necrosis induced by the anticancer drug cisplatin (CP). GABA was given orally (100 or 500 mg/kg/day for ten consecutive days), and on the 6th day, some of the treated rats were also injected intraperitoneally with either saline or CP (6 mg/kg). Four days after CP treatment, urine was collected from all rats, which were then anaesthetized for blood pressure and renal blood flow monitoring. This was followed by intravenous injection of norepinephrine for the assessment of renal vasoconstrictor responses. Thereafter, blood and kidneys were collected for measurement of several functional, biochemical and structural parameters. GABA treatment (at 500 but not 100 mg/kg) significantly mitigated all the measured physiological and biochemical indices. Sections from saline- and GABA-treated rats showed apparently normal proximal tubules. However, kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with GABA (500 mg/kg). The concentration of platinum in the cortical tissues was not significantly altered by GABA treatment. The results suggested that GABA can ameliorate CP nephrotoxicity in rats. Pending further pharmacological and toxicological studies, GABA may be considered a potentially useful nephroprotective agent in CP-induced ARI.
authors: Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Oman, UAE.
authors: Badreldin H
authors: BH
authors: Ali
authors: Suhail
authors: S
authors: Al-Salam
authors: Mohammed
authors: M
authors: Al Za'abi
authors: Khalid A
authors: KA
authors: Al Balushi
authors: Ahmed S
authors: AS
authors: AlMahruqi
authors: Somyia
authors: S
authors: Beegam
authors: Intisar
authors: I
authors: Al-Lawatia
authors: Mostafa I
authors: MI
authors: Waly
authors: Abderrahim
authors: A
authors: Nemmar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002374:Catalase / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D006439:Hemodynamics; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000188:drug therapy*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D005680:gamma-Aminobutyric Acid; D003404:Creatinine; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D002945:Cisplatin