Effect of Pentylenetetrazole and Carbodiimide on Oxidation Stress Markers in Rat Brain

Abstract

A number of studies suggest that epileptic seizures are related to certain harmful functions of nitric oxide (Tsuda et al. 1998). This disorder can be induced with pentylenetetrazole, a drug that causes generalized seizures with abnormal levels of nitric oxide and serotonin (5-HT) (Balakrishnan et al. 1999). Analogous to pentylenetetrazole, carbodiimide participates in the biochemical metabolism of nitric oxide (Rotzingers et al. 1995), even though its mechanism of action remains unknown. Since nitric oxide is an unstable and gaseous free radical with a short half-life, its indirect measurement is possible as a result of the calculation of nitrites or nitrates. Diseases associated with epileptic seizures involve the role played by oxidative stress generated by the effect of free radicals (Bashkatova et al. 2003), where unknown biochemical mechanisms are related with lipid peroxidation levels (Ischiropoulos & Beckman 2003). The aim of the present study is to evaluate the effect of pentylenetetrazole and carbodiimide on some biochemical markers of oxidative stress as nitric oxide metabolites, 5HT, Naπ Kπ ATPase and thiobarbituric acid in rat brain. Twenty-four Wistar male adult rats (350 g) were divided into 3 groups of 8 animals: group I, control group 0.9% NaCl was given; group II treated with carbodiimide (20 mg/ kg), and group III, treated with pentylenetetrazole (40 mg/ kg), drugs were administered in a single intraperitoneal dose. After 10 min. the animals were decapitated and dissected in sagittal section: the tissue of left-sided section was used for the Naπ, Kπ-ATPase, and total ATPase assays, lipid peroxidation (TBARS), and levels of nitrites and nitrates. The right-sided section was used for determination of serotonin (5-HT). The inorganic phosphorus (Pi) content was measured using the method proposed by Balbonting et al. (1961), the difference of inorganic phosphorus content