Possible neuroprotective effect of some drugs modulating Nitric Oxide apoptotic pathway in L-2 chloropropionic acid-induced neuronal injury in rats

There is a recent evidence supporting that neuronal injury may be dependent upon the generation of the free radical nitric oxide [NO] with the subsequent induction of programmed cell death [apoptosis]. The aim of the present study was to assess the contribution of NO and the possible neuroprotective effect of two drugs modulating NO-apoptotic pathway, namely minocycline and ebselen, in L-2 chloropropionic acid [L-CPA] -induced neuronal injury in the rat. The present study was conducted on 40 male albino rats that were divided into: Group I; normal rats that served as control Group II; rats in which cerebellar neuronal injury was induced by L-CPA, Groups III and IV; rats with L-CPA -induced neuronal injury that received minocycline and ebselen respectively for 2 days starting half an hour before dosing with L-CPA. Forty-eight hours following L-CPA administration, signs characteristic of cerebellar ataxia, including hind limb weakness and abnormal gait were recorded, The ability of the rat to lift [retract] its hindlimbs was measured. Rats were then exsanguinated, cerebellum isolated for the determination of cerebellar: Nitric oxide synthase [NOS] activity, caspase-3 activity as an index of apoptosis, sodium concentration as a measure of cerebellar edema and glutamate concentration as a marker for cerebellar granule cell necrosis. The results of the present study demonstrated a significant increase in: the time taken by rats to retract hindlimbs, cerebellar NOS and caspase-3 activities as well as in sodium concentration, in group II compared to group I. A significant decrease in cerebellar glutamate concentration could be observed in group II compared to group I. Treatment with minocycline and ebselen resulted in significant decrease in cerebellar NOS activity and active caspase-3 and sodium concentrations together with a significant increase in cerebellar glutamate concentration compared to non-treated rats receiving L-CPA. In conclusion, the present work demonstrated that neuronal injury, induced by L-CPA, is associated with increased NOS activity resulting in increased NO production, which has been suggested to play a role in the mediation of that injury. We demonstrated that drugs that reduce the activity of NOS and caspases, like minocycline and ebselen are capable of blocking neurotoxicity. These results provide an experimental rationale for the evaluation of the role of NO-apoptotic pathway and the possible therapeutic potential of minocycline and ebselen in human neurological disorders

Study of the mechanism underlying the prokinetic action of erythromycin on lower esophageal sphincter pressure in dogs

Erythromycin [EM] and a number of its derivatives exhibit prokinetic properties. In particular, the drug increases the contractile activity of smooth muscles of esophagus and promotes gastric emptying in both health and disease. The drug enhances esophageal and gastric motility by acting as a motilin agonist. The aim of the study was to evaluate the effect of low dose of EM, as a prokinetic agent, on the lower esophageal sphincter pressure [LESP] and to study the receptors involved in the mediation of the prokinetic action of EM. The study was carried out on 30 adult healthy dogs [10-15 kg] divided into five groups, each group consisted of 6 dogs. The studied groups were: I: a control group [placebo treated], II: an erythromycin treated group [EM gp] [7 mg/kg b.w. by i.v.i], and three groups III, IV, V that were treated with EM [7 mg/kg b.w. i.v.L preceded by either atropine [a muscarinic blocker] in a dose of 40 micro ag/kg b.w. i.v.i., ondansetrone [5 HT3 antagonist] in a dose of 0.1 mg/kg b.w. i.v.i or metoclopramide [dopamine receptor type 2 antagonist] in a dose of 150 micro g/kg b.w. i.v.i. respectively. After an over night fasting, basal recording of LESP was carried out in each group by an esophageal manometer connected to a pressure transducer. LESP was recorded for all animals in all groups fifteen minutes after the end of the predescribed treatments. Data obtained showed that EM significantly increased the resting LESP. Pretreatment with either atropine or ondansetrone totally prevented the increase in LESP induced by EM. However, pretreatment with metoclopramide failed to prevent the increase in LESP induced by EM. The findings suggest that EM in a low, subantimicrobial dose has a prokinetic action on the lower esophageal sphincter. It was found that this prokinetic action is exerted most probably by stimulating cholinergic pathway and strongly suggested that 5 HT3 receptors are involved in this process. Meanwhile, the dopaminergic receptors seem to have no role in the mediation of this prokinetic action of EM. It is hoped that this prokinetic action of EM could be of a particular benefit in the improvement of GIT motility disorders. However this warrants further investigation to help more understanding of cellular mechanisms regarding that effect of EM

Serum tumor necrosis factor- alpha, interleukin-6 and vitamin D therapy in acute renal failure in rats

The aim of this study is to show the relation between the levels of TNF-alpha, IL-6 and acute renalfailure, also the effect of Vit D3 therapy on the level of these cytokines 30 male rats were used. They were subdivided into 2 groups: group 1: 10 rats as controls, Group II was subdivided into 2 subgroups: Group II A: 10 rats with gentamicin model of acute renal failure, Group II B: 10 rats received vit D3 [450 IU/Kg/d] orally for one month prior to induction of renal failure as in group II A. The following parameters were measured: Creatinine clearance, urea concentration, urinary albumin, serum TNF - alpha and serum IL - 6 levels. TNF-alpha and IL - 6 were elevated in rats with acute renal failure. vit D3 therapy, resulted in reduction of their levels. TNF-alpha and IL-6 could he implicated in this model of acute renal failure. Vit D[3] can produce significant change in the level of these cytokines. TNF-alpha antagonists holds promise for the treatment and prevention of acute renal failure

Effect of chronic lead exposure on functions and urinary excretion of some essential metals in rats

The present study was carried out on 20 male albino rats [lead exposed group and control group each of 10 rats]. Creatinine clearance, serum uric acid, serum glucose, urinary excretion of zinc, iron, copper, uric acid and serum glucose levels, also increased urinary excretion of the essential elements. It can be concluded that lead nephropathy can be related to impaired metabolism and diverse function of not only calcium but also other cations as zinc, iron, copper and magnesium