Lamotrigine and liver in stressed rats

What is it about?

The present study is designed to investigate the possible hepatotoxic effects of the anti-epileptic drug “lamotrigine, LTG” in adult male wister rats after picrotoxin –induced convulsions and exposure for 21 days to chronic restraint model. This was done by a trial to find out alterations in the activities of liver enzymes and some antioxidants in this model of co-morbidity. They were treated by gastric gavage with LTG [20mg/kg body wt.] for 21days. Then rats were anesthetized and dissected to remove liver and to collect blood. Selected liver enzymes [AST, ALT] and some anti-oxidant enzymes were assayed. The results indicated that the drug significantly increased the activities of glutathione peroxidase and catalase enzymes in hepatic homogenates, while it significantly decreased the level of the lipid peroxidation expressed as thiobarbituric acid-reactive substance (TBARS) in these homogenates. However, there was an elevation of tested liver enzymes ALT & AST at the end of 21 days. This revealed the occurrence of possible hepatocellular damage. The present study recommends a regular liver function and drug monitoring during the therapeutic use of this drug in epilepsy-stress comorbidity.

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Why is it important?

The management of epilepsy-stress comorbidity by lamotrigine (LTG) could be associated with possible beneficial anti-oxidant actions on different body organs in addition to its anti-convulsant effect in mice exposed to a chemoconvulsive model. The later effect could be partially related to a decrease in levels of some oxidative stress markers as TBARS with an increase in anti-oxidant enzymes e.g. catalase and glutathione peroxidase enzymes as proved in the present study. Clinically, a strong recommendation of a careful monitoring of liver function tests and lamotrigine ( LTG) drug monitoring should be done while treating stressed epileptic patients with LTG, with an avoidance of the prescription of large doses as far as possible, especially in people who live in developing countries with the presence of a large percentage of them suffering from endemic hepatitis.