Scientia Pharmaceutica

M. Raza ¹, O. A. Al-Shabanah ¹, T. M. El-Hadiyah ¹, A. A. Al-Majed ¹

Affiliations
1 Department of Pharmacology, College of Pharmacy, King Saud University, P O Box 2457, Riyadh 11451, SA

Abstract

We have evaluated vigabatrin (γ-vinyl γ-aminobutyric acid), an irreversible inhibitor of γ-aminobutyric acid (GABA)-transaminase responsible for GABA degradation, for its effects on food consumption, body weight changes, fluid intake, changes in hematological and biochemical parameters in plasma liver and kidney of Swiss albino mice. Mice received vigabatrin 0.26% wlv chronically in drinking water for 7, 14 and 21 days. Changes in all the parameters were recorded after 7, 14 and 21 days respectively in different groups. Food consumption was comparable to the control group with minor fluctuations. The body weight declined significantly but only after 3-week treatment with no appreciable change in organ indices or relative organ indices. There were essentially no adverse effects on hematological parameters (RBC, WBC, HGB, neutrophils, eosinophils, monocytes, lymphocytes and basophils) with this treatment. However, there was a decrease in monocyte counts during the first week and an increase in the neutrophil counts during the third week of vigabatrin treatment. In one part plasma biochemical parameters like AST, ALT, CK-MB, creatinine, glucose and urea were also assessed with the same dose regimen. It was observed that only CK-MB and GPT activity levels were altered slightly significantly and are thought to be a result of cross enzyme inhibitions. In this experiment it was observed that lipid peroxide levels measured, as malondialdehyde did not change appreciably in both liver and kidney tissues. However, the levels of glutathione (non-protein sulfhydryl; GSH) declined significantly in comparison to control in liver and kidney. A comparison of level of GSH in liver and kidney shows that this depletion was at early time points in the former. The depletion of GSH suggests the possible involvement of GSH in detoxification process and corroborates its role in protection.

Keywords

Vigabatrin, Hematology, Plasma, Liver, Kidney, Biochemistry

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