In vitro study on the effect of histamine H2 receptor antagonism on neuromuscular transmission

The effect of varying concentrations of the histamine H2-receptor antagonists; nizatidine, ranitidine and famotidine on neuromuscular transmission was examined using isolated toad rectus abdominis muscle. Also, the possible interaction between the H2- receptor antagonists and the non-depolarizing neuromuscular blocker D-tubocurarine was investigated. Isolated total toad rectus abdominis muscle preparations were exposed to increasing concentrations of acetylcholine [Ach] to obtain full concentration- response curves, then the effects of two concentrations of nizatidine, ranitidine and famotidine, on the contractile effect of Ach was examined. Also, the effect of D-tubocurarine on the contractile effects of Ach in the absence and in the presence of chosen concentrations of the H2-receptor antagonists was examined. Nizatidine and ranitidine at low concentrations augmented and at higher ones inhibited the Ach-induced contractions of the toad rectus abdominis, while famotidine at the two concentrations used lack a significant effect on the contractile effect of Ach. In addition, nizatidine and ranitidine at a low concentration antagonized the D-tubocurarine blocking activity on the Ach induced contractions, but at high concentration they augmented D-tubocurarine's effect. In contrast famotidine did not alter the inhibitory effects of D-tubocurarine on Ach-induced contractile response

Conclusion: The present study suggests that nizatidine and ranitidine probably possess either anticholinesterase-like effect or neuromuscular blocking effect, depending on their concentration. Confirming this, low concentrations of these H2 antagonists antagonized the neuromuscular blocking activity of D-tubocurarine while their high concentrations potentiated the effect of D-tubocurarine. In contrast famotidine did not alter the contractile effect of Ach or the D-tubocurarine neuromuscular blocking activity. This would suggest that nizatidine and ranitidine should be used with caution for premedication purpose, anticipating clinically relevant drug interactions with neuromuscular blockers while famotidine, could be considered safer in premedication. Yet, further clinical studies are needed

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