Impact of gamma-aminobutyric acid receptors modulators on renal and liver functional, molecular and histological characteristics in white male mice

The gamma-aminobutyric acid (GABA) receptors are considered the main receptors that inhibit neurotransmitters in the mammalian brain, and they have been proven to exist in non-neuronal cells. The study's purpose is to determine the impact of GABA modulation on renal and liver functions and molecular and histological characteristics using different doses of lorazepam. Lorazepam, one of the benzodiazepine drugs known for its modulatory effect on GABA receptors, has been used as a modulator to determine the impact of GABA modulation on renal and liver functions and molecular and histological characteristics in 30 albino male mice, out of which 21 were divided into 3 groups. Each group were treated with different dose of lorazepam (1 mg/kg, 2 mg/kg and 3 mg/kg body weight respectively). The rest 9 of animals were considered as a control group. Histological and functional parameters were studied in kidney and liver functional states to evaluate the impact of GAPA modulation using lorazepam. Total genomic DNA was extracted from liver, brain, kidney and blood and random amplification polymorphic DNA (RAPD) technique were used to detect the molecular impact of GABA modulation on the genomic DNA. The data were analyzed using SPSS Version 20.0 (SPSS Inc.), with means and standard deviations (SD) calculated for quantitative variables, and ANOVA applied for comparing group means. Functional parameters (blood urea, creatinine, GOT, GPT, GGT) and histopathological examination showed a significant change in treated groups compared to the control group. In both the liver and kidneys of mice, with increasing doses of lorazepam, there was an increase in the severity of congestive phenomena in blood vessels with the appearance of hemorrhages, signs of inflammation, and cell degeneration and necrosis. The molecular investigation indicated substantial changes in RAPD profiles of treated groups, with normal bands disappearing and novel bands appearing in contrast to the control group. The RAPD profiles of the treated and control samples revealed 432 bands, with 109 as control bands, 167 (loss of normal bands and emergence of novel bands) as polymorphic bands, and 156 as homomorphic bands. It is concluded that GABA modulation by lorazepam increases the functional and histopathological alterations, producing variations in the genomic DNA.