Clinical and experimental evaluation of some unwanted effects of sodium valproate

The aim of the present work was to evaluate some side effects induced by sodium valproate in epileptic patients. Moreover, to study the effect of the drug on brain chemical neurotransmitters, namely GABA and 5-HT: to confirm its anticonvulsant effect and to exptain some of its side effects. This study was carried out in 2 parts: clinical and experimental. The clinical part was done by clinical evaluation of side effects of sodium valproate on 40 epileptic patients receiving it for at least 3 months. Liver function tests and serum prolactin level were also done before and after treatment. The experimental part was carried out on 30 rats receiving the same drug, and another 30 rats as a control group. Measurements of GABA and 5-HT in different brain areas in both groups was done. Liver biopsy was taken also from both groups and examined under light microscope. The results of the study revealed that side effects appeared in 35% of patients. Weight gain [in 15%], increased appetite, gastrointestinal disturbances and tremors were the commonest side effects. But sedation, headache and skin rashes were less common. The effect of sodium valproate on hepatic enzymes showed significant [P /= 0.05] on serum prolactin level. Moreover, sodium valproate significantly elevates GABA in different areas of brain, and 5-HT in cerebral cortex and midbrain. There was significant reduction of 5-HT level [P

Reduction of chemically induced hepatitis in rats by adenosine

The protective effect of adenosine [1 mg/kg LP.] in hepatitis induced experimentally in rats with dgalactosamine [800 mg/kg LP.] was assessed. The degree of protection was determined biochemically by measuring AST, ALT and bilirubin in addition to hepatic nitric oxide, and by histo-pathological examination of liver. In d-galactosamine induced hepatitis in rats, there were significant elevation of ALT, AST, bilirubin and NO2 and NO3 in addition to foci of necrosis and infiltration of lymphocytes in hepatic lobules and portal tracts. In rats treated with adenosine [1 mg/kg LP.] there were significant reduction of ALT, AST, bilirubin and NO2 and NO3 in addition to more or less normal histological picture of liver. In conclusion, these findings revealed that adenosine had a protective anti-inflammatory effect on liver and this effect may be due to a reduction of hepatic nitric oxide

Effect of guanfacine on kidney, heart and GABA level in DOCA and salt hypertensive rats

Experimental hypertension, was induced in rats by intramuscular injection of desoxycorticosterone [DOCA] in a dose of 50 mg/kg body weight/week for six weeks, in addition to salt in drinking water. Guanfacine was given to normotensive and hypertensive rats intraperitoneally in a daily dose of 0.09 and 0.18 mg/kg body weight for 30 days. Induction. of hypertension resulted in significant reduction in the neurotransmitter gamma aminobutyric acid [GABA] concentration in the brain, hypertrophy of the cardiac muscle and nephrosclerosis with impaired renal function. However, these histophathological and biochemical changes were paradoxically decreased after giving guarifacine in a daily dose of 0.09 mg/kg body weight for 30 days, as a result of marked decrease of blood pressure. The hypertensive rats treated with 0.18 mg/kg body weight of guanfacine for 30 days showed marked increase in the incidence and severity of cardiac and renal histopathological changes, due to the combined toxic effect of guanfacine and hypertension. The increased GABA concentration in the brain and the reduction in blood pressure after giving the drug were more significant with the low dose. In normotensive groups, rats treated with guanfacine in a daily dose of 0.18mg/kg body weight for 30 days showed moderate renal toxicity, while no biochemical or histopathological changes were observed with 0.09 mg/kg body weight of guanfacine. The two doses of guanfacine induced insignificant changes in both blood pressure and GABA concentration in the brain as compared to control non-treatment rats. Thuse law dose of guanfacine is considered more effective and safe and so it is superior to high dose in the ambulatory treatment of hypertension

Serum immunoglobulin level in Egyptian male schizophrenics under chlorpromazine treatment

This work was carried out to study serum immunoglobulin [Ig] levels in chronic Egyptian schizophrenics and the possible effects of chlorpromazine [CPZ] medication on them. Results of the present work revealed that there was significant elevation [P <0.05] of serum IgM, IgG, and IgA in schizophrenics compared with control healthy group. Moreover, in schizophrenics under CPZ treatment there was significant rise [P <0.05] in serum IgG, IgM and IgA compared with control healthy group, but IgM level was significantly elevated [P <0.05] compared with schizophrenic group. In addition, there were nonsignificant differences [P> 0.05] in serum albumin or total protein. In conclusion, increased Ig levels may suggest that schizophrenia might be caused by viral infections or may be an autoimmune disease. Moreover, stimulation of immune system by CPZ may explain the resistance of schizophrenics to CPZ treatment. It can be recommended that patient who develop an increase in serum IgM while on CPZ be switched to other type of antipsychotic medications

study of the effect of sodium valproates on brain neurotransmitters GABA and 5HT and its teratogenic effect an experimental study

White albino rats were given sodium valproates 400mg / kgm / day for 21 days in males and till 20th day of gestation in females compared to other group of rats didn't receive any drug. The effect of the drug on rats showed significant elevation of GABA concentrations in all tested brain areas and 5HT in cerebral cortex and midbrain, while reduced 5HT in thalamus and hypothalamus. Maternal adminstration of Sodium Valproates induced non Significant change in the number of resorption and live fetuses, as well as number of implantation. Fetuses revealed spina bifida [30%], absence of angle of mandible and ossific centers in upper and lower limbs [15%] and short neck [15%]. Side effects of sodium Valproates such as sedation and weight gain could be attributed to increase of GABA concentration, whereas increased appetite may be due to decreased 5HT in hypothalamus. The anticonvulsant effect of Sodium Valproates could be due to such increase of GABA and to some extent incease of 5HT