Enhanced inhibitory effects of gamma-aminobutyric acid on renal and hepatic function, molecular profiles, and histological changes in male albino mice.

Abstract

Background: The gamma-aminobutyric acid (GABA) receptors are considered the main inhibitory neurotransmitter receptors in the mammalian brain and they have been proven to be existing in non-neuronal cells.

Aim: Lorazepam which is one of the benzodiazepines, drugs known for their effect of GABA receptors, has been used in this study as an enhancer to determine the impact of GABA activity enhancement on renal and liver functions, molecular and histological characteristics in male albino mice.

Methods: Male albino mice were divided into 3 groups (each has 7 animals) each group was treated with a different dose of lorazepam and 9 animals served as a control group. The molecular parameters included the usage of raped-polymerase chain reaction to detect any universal variations. The histological changes were detected using hematoxylin and eosin histopathological examination. Liver and kidney function tests were utilized to detect any functional changes.

Results: The results of the functional parameters [serum urea, creatinine, glutamate-oxaloacetic transaminase, glutamate-pyruvic transaminase, gamma glutamyl enzyme (GGT)] and histopathological examination demonstrated that there was a significant change in treated groups compared to the control group. As for the molecular study, 7 primers out of 10 gave single and polymorphic bands using the random amplification of polymorphic DNA (RAPD) technique. The results revealed great changes in RAPD profiles of treated groups as normal bands lost and new bands appeared in comparison with the control group. The RAPD profiles of the treated and control samples gave 432 bands, 109 as control bands, 167 (loss of normal bands and appearance of new bands) as polymorphic bands, and 156 as homomorphic bands.

Conclusion: The marked changes in various biochemical, histopathological, and random amplified polymorphic DNA-polymerase chain reaction profiles indicate that lorazepam-mediated GABA modulation brings about widespread alterations in peripheral organ systems. Taken together, these data suggest caution in the use of lorazepam clinically and potentially represent an unmet need for safer therapeutic alternatives or strategies to limit benzodiazepine-induced organ toxicity.