Effect of l-carnitine and deferoxamine on hepatotoxicity, erythrocyte ergothioneine and testicular testosterone synthesis in sodiumvalproate-treated rats

The aim of the present study was to evaluate the effect of sodium valproate [VPA] as anantiepileptic drug on liver and erythrocyte oxidative state and on testicular testosterone synthesis. The therapeuticefficacy of either L-carnitine or deferoxamine [DFO] was assessed in such situations. This study included 108 albino rats divided into control groups, single dose VPA treated groups withand without L-carnitine or DFO treatment and repeated dose VPA treated groups with and without L-carnitine orDFO treatment. Liver triglycerides and malondialdehyde levels and catalase and glutathione S transferaseactivities as well as erythrocyte ergothioneine were estimated. In testes, P450cl7 and 17/3 hydroxysteroiddehydrogenase activities were measured as testosterone synthesis. Single and repeated VPA administration caused an increase in liver triglycerides, malondialdehyde,catalase and glutathione S transferase and a decrease in erythrocyte ergothioneine. Only repeated VPAadministration could decrease testicular testosterone synthesis. Co-administration of L-carnitine or DFO withVPA resulted in improvement of all the studied parameters. These data support the oxidative stress as a possible mechanism implicated in VPA-induced liver anderythrocyte damage. Moreover, VPA could alter testosterone synthesis giving a possible link between malereproductive function and VPA. The protective influence of L-carnitine and DFO may be partly mediated by theirantioxidant effects and by improving gonadal testosterone synthesi

Texicological, histopathological and ultrastructural study of the protective effects of some antioxidants on sodium valproate induced hepatotoxicity in rats

Valproic acid [VPA] is well known for its broad spectrum antiepileptic activity and is gaining popularity as a component in antipsychotic therapy. VPA may have limited use due to the possible risk of hepatotoxicity. The aim of the present work was to investigate the hepatotoxic effect of VPA and to evaluate the protective role of deferoxamine and L-carnitine. The levels of malonaldehyde [MDA], antioxidant enzymes [catalase and glutathione -S-transferase] and liver triglycerides were measured in the liver tissues. In addition, serum levels of liver enzymes and plasma triglycerides were measured. Histological and ultrastructural changes in the hepatocytes were studied. The results showed that, VPA- induced hepatotoxicity was in the form of micro vesicular steafosis. Biochemically, evidence of oxidative stress namely, elevated levels of MDA, catalase and glutathione -S- transferase were found. Increased levels of liver enzymes and plasma and liver triglycerides were also detected. Co-administration of deferoxamine with VPA resulted in protection of the hepatocytes against VPA induced hepatotoxicity. Co-administration of L-carnitine with VPA was associated with better results than deferoxamine histologically, ultrastructurally and biochemically. In conclusion, the use of L-carnitine as an antioxidant in protecting against valproat induced hepatotoxicity should be encouraged

Toxicological, histopathological and ultrastructural study of the protective effects of some antioxidants on sodium valproate induced hepatotoxicity in rats

Valproic acid [VPA] is well known or its broad spectrum antiepileptic activity and is gaining popularity as a component in antipsychotic therapy. VPA may have limited use due to the possible risk of hepatotoxicity. The aim of the present work was to investigate the hepatotoxic effect of VPA and to evaluate the protective role of deferoxamine and L-carmitine. The levels of malonaldehyde [MDA], antioxidant enzymes [catalase and glutathione-S-transferase] and liver triglycerides were measured in the liver tissues. In addition serum levels of liver enzymes and plasma triglycerides were measured. Histological and ultrastrucural changes in the hepatocytes were studied. The results showed that, VPA-induced hepatotoxicity was in the form of microvesicular steatosis. Biochemically, evidence of oxidative stress namely, elevated levels of MDA, catalase and glutathione-S-transferase were found. Increased levels of liver enzymes and plasma and liver triglycerides were also detected. Co-administration of deferoxamine with VPA resulted in protection of the hepatocytes against VPA induced hepatotoxicity. Co-administration of L-carnitine with VPA was associated with better results than deferoxamine histologically, ultratructurally and biochemicaly. In conclusion, the use of L-carnitine as an antioxidant in protecting against valproat induced hepatotoxiciy should be encouraged

Memantine hydrochloride versus pralidoxime in the treatment of chlorpyrifos - induced pulmonary toxicity in albino rats

Chlorpyrifos [CP] is a broad-spectrum organophosphorus insecticide that is widely employed for control of many agricultural and household pests. It is extremely toxic to humans and animals. The antidotal therapy of acute organophosphorus poisoning hasn't been satisfactorily solved till now in spite of the knowledge of the basic mechanism of action of these toxic substances. The aim of this work was to investigate the effect of acute CP intoxication on the alveolar structure of albino rats and to compare the therapeutic efficacy of memantine hydrochloride [MEM]k, and amantadine derivative, and the currently used oxime [pralidoxime chloride [2-PAM] Six groups of rats were used in this study, each of ten animals. The control groups [group I, II, III], The intoxicated group [group IV that received CP in a dose of 40 mg/kg body weight orally for two consecutive days and the treated groups which, included group V [rats treated with PAM and atropine sulfate [ATS] for 2 days]. Blood samples were collected from all animals one hour after drug administration for estimation of plasma acetylcholinesterase [AchE] enzyme level. The animals were sacrificed 24 hours after the last injection and the lungs of each animal were examined histologically by the light and the transmission electron microscopes. The present study demonstrated significant reduction in the level of plasma AchE in CP group. On he other hand, the enzyme levels increased in both groups of CP and MEM and CP and 2-PAM [but still less than normal control levels]. The enzyme reactivation was much more evident with MEM treatment. Histologically, CP treatment resulted in severe pulmonary congestion with extravasation of blood cells, thickening of pulmonary interstitial and evident ultratructural aerations of the alveolar structures. Treatment with MEM after CP resulted in greater alternations of CP-induced alveolar lesions than 2-PAM treatment. In conclusion, he results of this study suggested that CP is a potent pulmonary toxicant, and MEM is more effective reactivator of CP-inhibited AchE than 2-PAM. It also offered greater alveolar protection than 2 PAM

Histological study of the effect of haloperidol on the corpus striatum of Albino rats and the possible neuro-protective role of vitamin E

Halperidol [HP] is a high potency antipsychotic drug used in treatment of schizophrenia. One of its major side effects is Tardive Dyskinesia [TDD] which is a syndrome of irreversible involuntary movements in tongue, face, arms and legs. Different mechanisms were proposed to explain the pathphysiology of TD and to suggest the proper treatment of this iatrogenic effect caused by HP. The most accepted theory could be histological alterations in the striatum caused by an oxidative stress mechanism and hence the trial of vitamin E [being an antioxidant] as a protective agent against HP-induced TD. The study was performed to investigate the effect of HP on the corpus striatum of rat and the possible neuroprotective role of vitamin E. The present study was carried out on forty adult male albino rats which were divided into four groups; the control group, vitamin E group received only vitamin E orally in a dose of 100 mg/kg/day for 4 consecutive weeks, the HP group received HP in a dose of 40 mg/kg/day for 4 consecutive weeks and the HP and vitamin E group received 100 mg/kg vitamin E in conjunction with HP for the same period. Clinical observation for VCMs [analogue of TD] was made during the period of experiment. At the end of four weeks, animals were sacrificed and brain specimens were prepare for histological study of the basal ganglia by light microscopy using H and E. and DOPA reaction. There were different histological alternations in neurons of the striatum in the HP-treated group, which were in the form of distortion, cellular infiltration,, shrinkage and hypereosinophilia of the cytoplasm. Other neurons showed cytoplasmic vacuolations, Co-administrations of vitamin E, reduced the HP-induced striatal neuronal changes, thus, vitamin E could be of value as a neuroprotective agent against HP-induced striatal changes in humans