The Protective Effect of γ‑aminobutyric Acid on Kidney Injury Induced by Renal Ischemia‑reperfusion in Ovariectomized Estradiol‑treated Rats

Abstract

Background: Renal ischemia‑reperfusion injury (IRI) is one of the most important causes of kidney injury, which is possibly gender‑related. This study was designed to investigate the role
of γ‑aminobutyric acid (GABA) against IRI in ovariectomized estradiol‑treated rats.

Methods: Thirty‑five ovariectomized Wistar rats were used in six experimental groups. The first three groups did not subject to estradiol treatment and assigned as sham‑operated, control, and
GABA‑treated groups. GABA (50 μmol/kg) and saline were injected in the treated and control groups 30 min before the surgery, respectively. The second three groups received the same treatments but received estradiol valerate (500 μg/kg, intramuscularly) 3 days prior to the surgery.
The IRI was induced in the control and treated groups by clamping the renal artery for 45 min and then 24 h of reperfusion. All animals were sacrificed for the measurements.

Results: The serum levels of creatinine and blood urea nitrogen, kidney weight, and kidney tissue damage score significantly increased in the IRI rats (P < 0.05). GABA significantly decreased
the aforementioned parameters (P < 0.05). The uterus weight increased significantly in rats that received estradiol (P < 0.05). Serum and kidney levels of nitrite (nitric oxide metabolite) did not alter significantly. Serum level of malondialdehyde increased significantly in the ovariectomized rats exposed to IRI (P < 0.05).

Conclusions: It seems that GABA improved IRI in ovariectomized rats. Estradiol was also nephroprotective against IRI. However, co‑administration of estradiol and GABA could not protect
the kidney against IRI.

Keywords: Estradiol, γ‑aminobutyric acid, ovariectomized rats, renal ischemia‑reperfusion