Hypericum Perforatum Decreased Hippocampus TNF-alpha and Corticosterone Levels with No Effect on Kynurenine/Tryptophan Ratio in Bilateral Ovariectomized Rats

The present study was designed to investigate the effect Hypericum Perforatum (HP), on behavioral changes, corticosterone, TNF-alpha levels and tryptophan metabolism and disposition in bilateral ovariectomized rats compared to 17alpha -ethinylestradiol. Behavioral analysis by measuring immobility time in forced swimming test and open field test, serum and hippocampal corticosterone and TNF-alpha along with hippocampal kynurenine/tryptophan ratio were determined in mature ovariectomized rats treated orally either by HP at three different doses 125, 250, and 500 mg/kg/day or by 17alpha-ethinylestradiol 30 microg/kg/day for 30 days. Ovariectomized rats showed significant increase in immobility time in the forced swimming test. Along with elevation in serum and hippocampal TNF-alpha and corticosterone levels associated with significant increase in hippocampal kynurenine/tryptophan ratio. Immobility time in the forced swimming test was decreased in rats treated by different doses of HP in a dose dependent manner and 17alpha-ethinylestradiol with no concomitant changes in the open field test. Only Rats treated with HP exhibited significant decrease in the elevated serum and hippocampal TNF-alpha and corticosterone, which couldn't explain the associated insignificant effect on hippocampaus kynurenine/tryptophan ratio in comparison to ovariectomized untreated rats. It is concluded that increased tryptophan metabolism toward kynurenine secondary to elevated corticosterone and TNF-alpha might be one of the pathohphysiological mechanisms that could explain depression like state observed in this rat model. Further, the observed attenuating effect of HP on TNF-alpha and corticosterone could contribute in its antidepressant effect in this animal model by other ways than their effects on tryptophan-kynurenine metabolism pathway.

Lamotrigine Decreased Hippocampal Damage and Improved Vascular Risk Markers in a Rat Model of Pentylenetetrazole Induced Kindling Seizure

Various antiepileptic drugs (AEDs) especially enzyme-inducing AEDs might be associated with increased vascular risk, through impairment of the endogenous antioxidative ability which may trigger oxygen-dependent tissue injury. Lamotrigine (LTG) a non-enzyme-inducing AED has scarce information regarding its effects on oxidative stress. The present study aimed to study the possible modulation of vascular risk factors of epileptogenesis by LTG, in a rat model of kindling seizure induced by pentylenetetrazole (PTZ). Four groups of male Wister rats were used; vehicle control group, PTZ group (alternate day PTZ, 30 mg/kg, i.p), LTG/PTZ group (LTG 20 mg/kg/day p.o and alternate day PTZ) and LTG group. The study period was 5 weeks. Lipoproteins and total homocysteine (tHcy), malondialdehyde (MDA) and reduced glutathione (GSH) were measured. Aortic endothelial function study and histopathological examination of the rats' brains, aortas and coronaries were conducted. Serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), tHcy, MDA, GSH levels were significantly higher in epileptic rats than normal controls rats. A decrease in HDL-cholesterol with high atherosclerotic index was also demonstrated. The administration of LTG improved the PTZ-kindled seizures. It produced a significant decrease in TC, TG and LDL-cholesterol, MDA, aortic GSH and increase in HDL-cholesterol with no significant effect on serum GSH and tHcy levels. LTG improved endothelium-dependent relaxation, decreased hippocampal neurodegenerative changes and atherosclerotic changes of aortas and coronaries. LTG decreased seizures severity, hippocampal damage and improved vascular risk markers in this rat model of kindling seizures.