Hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot (Prunus armeniaca L.) and its kernel against ethanol-induced oxidative stress in rats

The present study was carried to evaluate the hepatoprotective effect and antioxidant role of sun, sulphited-dried apricot and its kernel against ethanol-induced oxidative stress. The hepatopreventive and antioxidant potential of the plant’s supplementations were evaluated by measuring level of serum liver damage marker enzymes (AST, ALT, GGT and LDH), antioxidant defense systems (GSH, GR, SOD, GST and GPX) and MDA content in various tissues of rats. Eight experimental groups: I (control), II (20% ethanol), III (ethanol + 15% sun-dried apricot), IV (ethanol + 30% sun dried). V (ethanol + 15% sulphited-dried), VI (ethanol + 30% sulphited-dried), VII (ethanol + 15% kernel) and VIII (ethanol + 30% kernel). According to the results, the levels of serum enzymes increased significantly in the II group as compared to those of I group, but they decreased in the III, IV, V and VI groups as compared to those of II group. Also, administration of sun and sulphited-dried apricot supplementation restored the ethanol-induced imbalance between MDA and antioxidant system towards near normal particularly in tissues but not its kernel. It is concluded that apricot has a hepatoprotective effect in rats with ethanol, probably acting by promoting the antioxidative defense systems.     

Neuroprotective effect of ginger on anti-oxidant enzymes in streptozotocin-induced diabetic rats

The aim of the present study was to investigate the effect of ginger on oxidative stress markers in the mitochondrial fractions of cerebral cortex (CC), cerebellum (CB), hippocampus (HC) and hypothalamus (HT) of diabetic rats. Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage. A marked decrease in anti-oxidant marker enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), reduced glutathione (GSH) and increase in malondialdehyde (MDA) was observed in the diabetic rats. Decreased activities of anti-oxidant enzymes in diabetic rats were augmented on oral administration of ginger. Moreover, ginger administration depleted the MDA level, which was earlier increased in the diabetic rats. These results suggest that ginger exhibit a neuroprotective effect by accelerating brain anti-oxidant defense mechanisms and down regulating the MDA levels to the normal levels in the diabetic rats. Thus, ginger may be used as therapeutic agent in preventing complications in diabetic patients.     

Combined treatment with exogenous estradiol and progesterone increases the incidence of breast cancer in TA2 mice without ovaries

TA2 mice have a high incidence of spontaneous breast cancer without chemical stimulus. There are two proposed explanations for this phenomenon: one is gravidity and the frequency of pregnancies, and the other is related to the presence of the mouse mammary tumor virus (MMTV). MMTV is hormonally regulated and indirectly promotes tumor formation by leading to the activation of Wnt oncogenes through insertional mutagenesis. In order to clarify the relationship between estrogen, progesterone, MMTV, Wnt oncogenes and breast cancer, ovaries from virgin female TA2 mice were removed and the mice were treated with exogenous estradiol and progesterone in different patterns. This study found that the combination of exogenous estradiol and progesterone induced breast cancer formation in TA2 mice without ovaries. MMTV-LTR mRNA exhibited the highest expression in tumor tissue from the combination treatment group (CT). Mammary tissue from mice in the CT group had the highest Wnt1, Wnt5a, Wnt5b and Wnt10b mRNA expression levels. These results indicate that estradiol and progesterone act in a synergistic manner to upregulate MMTV, which subsequently induces breast cancer in TA2 mice. Various members of the Wnt gene family may play specific roles in different stages of carcinogenesis in TA2 mice.     

滋阴清热方对MRL／1pr狼疮鼠皮质醇及糖皮质激素受体mRNA表达的影响

目的 观察MRL／1pr狼疮鼠皮质醇及糖皮质激素爱体（GR）mRNA表达的变化及滋阴清热方对其水平的影响,探讨中药减轻激素不良反应的机理。方法40只MRL／1pr狼疮模型鼠随机分为4组,即模型组、中药组、西药组、中西药组。分别给予生理盐水、滋阴清热方、强的松悬液、滋阴清热复方＋强的松悬液灌胃,均每日1次,每次0．5mL,连续用药10周。另选用昆明小鼠10只作为正常对照组。应用放射免疫法测定MRL／1pr狼疮鼠糖皮质醇水平,反转录酶一聚合酶链反应法（RT—PCR）检测GRmRNA,观察各组皮质醇、GRmRNA表达的变化。结果模型组血清皮质醇水平与正常组比较,P〉0．05,而GRocmRNA表达明显低于正常组（P〈0．05）。西药组GRαmRNA、GRBmRNA下调水平高于中药组和中西药组（P〈0．01或P〈0．05）。结论滋阴清热方可上调MRL／1pr狼疮鼠GRmRNA表达水平,从而增强糖皮质激素的临床疗效,减少激素不良反应。     

The 5-HT1-like receptors mediating inhibition of sympathetic vasopressor outflow in the pithed rat: operational correlation with the 5-HT1A, 5-HT1B and 5-HT1D subtypes

1. It has been suggested that the inhibition of sympathetically-induced vasopressor responses produced by 5-hydroxytryptamine (5-HT) in pithed rats is mediated by 5-HT₁-like receptors. The present study has re-analysed this suggestion with regard to the classification schemes recently proposed by the NC-IUPHAR subcommittee on 5-HT receptors.
2. Intravenous (i.v.) continuous infusions of 5-HT and the 5-HT₁ receptor agonists, 8-OH-DPAT (5-HT_1A), indorenate (5-HT_1A), CP 93,129 (5-HT_1B) and sumatriptan (5-HT_1B/1D), resulted in a dose-dependent inhibition of sympathetically-induced vasopressor responses.
3. The sympatho-inhibitory responses induced by 5-HT, 8-OH-DPAT, indorenate, CP 93,129 or sumatriptan were analysed before and after i.v. treatment with blocking doses of the putative 5-HT receptor antagonists, WAY 100635 (5-HT_1A), cyanopindolol (5-HT_1A/1B) or GR 127935 (5-HT_1B/1D). Thus, after WAY 100635, the responses to 5-HT and indorenate, but not to 8-OH-DPAT, CP 93,129 and sumatriptan, were blocked. After cyanopindolol, the responses to 5-HT, indorenate and CP 93,129 were abolished, whilst those to 8-OH-DPAT and sumatriptan (except at the lowest frequency of stimulation) remained unaltered. In contrast, after GR 127935, the responses to 5-HT, CP 93,129 and sumatriptan, but not to 8-OH-DPAT and indorenate, were abolished.
4. In additional experiments, the inhibition induced by 5-HT was not modified after 5-HT₇ receptor blocking doses of mesulergine.
5. The above results suggest that the 5-HT₁-like receptors, which inhibit the sympathetic vasopressor outflow in pithed rats, display the pharmacological profile of the 5-HT_1A, 5-HT_1B and 5-HT_1D, but not that of 5-HT₇, receptors.

     

Potent inhibition of both the acute and delayed emetic responses to cisplatin in piglets treated with GR205171, a novel highly selective tachykinin NK1 receptor antagonist

1. The effects of {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171, a selective tachykinin NK₁ receptor antagonist, were investigated on both the acute and delayed phases of cisplatin-induced nausea-like behaviour and vomiting in the conscious piglet.
2. Animals receiving cisplatin (5.5 mg kg⁻¹, i.v.) were observed for 60 h. Fifteen min prior to cisplatin infusion (T0_−15 min), eight piglets acting as controls received an intravenous injection of saline solution (1 ml kg⁻¹), whereas experimental animals received a single i.v. administration of {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171 (1 ml kg⁻¹) at a dose of 0.01 (n=8), 0.03 (n=8), 0.1 (n=8), 0.3 (n=16) or 1.0 (n=13) mg kg⁻¹. In eight additional piglets, {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171 (1 mg kg⁻¹) was administered 15 min before the onset of the delayed phase (T16_−15 min). A further five piglets received {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171 (1 mg kg⁻¹) every 6 h throughout the experiment.
3. The latencies of the first emetic episode (EE) and nausea-like behavioural episode (NE) increased in all experimental groups treated at T0_−15 min, and the total number of both EE and NE during the 60 h was reduced in a dose-dependent manner. In piglets treated at T0_−15 min with {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171 1 mg kg⁻¹, eight out of 13 (62%) did not vomit throughout the experiment. Animals treated with {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171 (1 mg kg⁻¹) at T16_−15 min exhibited an acute response to cisplatin but did not vomit during the delayed phase. The greatest inhibition of both nausea-like behaviour and vomiting was observed in piglets receiving multiple injections of {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171.
4. These results demonstrate the long-lasting anti-emetic effects of {"type":"entrez-nucleotide","attrs":{"text":"GR205171","term_id":"238470896","term_text":"GR205171"}}GR205171, and confirm the key role of substance P within the emetic reflex.

     

Heterogeneity of behavioural profile between three new putative selective D3 dopamine receptor antagonists using an ethologically based approach

The effects on behaviour of the putative selective D₃ dopamine receptor antagonists GR 103691, nafadotride and U 99194A were compared with those of the generic D₂-like antagonist haloperidol, using an ethologically based approach. Neither GR 103691 (0.008–1.0 mg/kg) nor nafadotride (0.025–1.6 mg/kg) influenced any element of behaviour. Conversely, U99194A (1.67–45 mg/kg) effected a dose-dependent stimulation of episodes of non-stereotyped sniffing, locomotion, chewing and eating, with some stimulation of rearing, and reduced baseline levels of grooming; thereafter, as sniffing and locomotion declined, stimulation of episodes of grooming emerged. Haloperidol (0.0008–0.1 mg/kg) failed to promote any element of behaviour and reduced baseline levels of grooming; responsivity to U99194A was antagonised by pretreatment with haloperidol. The lack of effect of GR 103691 (>100-fold D₃/D₂ selectivity) and nafadotride (10-fold D₃/D₂ preference), in contrast to the characteristic ‘‘ethogram’’ for U99194A (25-fold D₃/D₂ selectivity), indicated a fundamental difference in their mechanisms of action. This topography of responsivity to U99194A overlapped somewhat with the profiles of both D₂-like and D₁-like agonists, and its sensitivity to antagonism by haloperidol also indicated a dopaminergic basis thereto. However, differences among GR 103691, nafadotride and U99194A bore no relation to their relative selectivities for the D₃ receptor, and the basis thereof remains unclear. Theorising as to the behavioural role of the D₃ receptor may need to be tempered pending the identification of a range of chemically distinct D₃ antagonists of higher selectivity. Received: 14 August 1997/Final version: 10 October 1997     

Propolis alleviates aluminium-induced lipid peroxidation and biochemical parameters in male rats

Aluminium is present in many manufactured foods and medicines and is also added to drinking water during purification purposes. Therefore, the present experiment was undertaken to determine the effectiveness of propolis in alleviating the toxicity of aluminium chloride (AlCl₃) on biochemical parameters, antioxidant enzymes and lipid peroxidation of male Wistar Albino rats. Animals were assigned to 1 of 4 groups: control; 34 mg AlCl₃/kg bw; 50 mg propolis/kg bw; AlCl₃ (34 mg/kg bw) plus propolis (50 mg/kg bw), respectively. Rats were orally administered their respective doses daily for 70 days. The levels of thiobarbituric acid reactive substances (TBARS) was increased, and the activities of glutathione S-transferase, superoxide dismutase, catalase and glutathione peroxidase were decreased in liver, kidney and brain of rats treated with AlCl₃. While, TBARS was decreased and the antioxidant enzymes were increased in rats treated with propolis alone. Plasma transaminases, lactate dehydrogenase, glucose, urea, creatinine, bilirubin, total lipid, cholesterol, triglyceride and LDL-c were increased, while total protein, albumin and high HDL-c were decreased due to AlCl₃ administration. The presence of propolis with AlCl₃ alleviated its toxic effects in rats treated with AlCl₃. It can be concluded that propolis has beneficial influences and could be able to antagonize AlCl₃ toxicity.     

Chemoprevention of rat mammary carcinogenesis by Azadirachta indica leaf fractions: Modulation of hormone status,xenobiotic-metabolizing enzymes,oxidative stress,cell proliferation and apoptosis

We evaluated the chemopreventive potential of the ethyl acetate fraction (EAF) and methanolic fraction (MF) of Azadirachta indica (neem) leaf on 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary carcinogenesis. Estradiol and estrogen receptor status, xenobiotic-metabolizing enzyme activities, redox status, DNA and protein modifications, and the expression of cell proliferation, and apoptosis related proteins in the mammary gland and liver were used as biomarkers of chemoprevention. Administration of both EAF and MF at a dose of 10 mg/kg bw effectively suppressed tumour incidence. Chemoprevention by neem leaf fractions was associated with modulation of hormone and receptor status, xenobiotic-metabolising enzymes, and lipid and protein oxidation, with upregulation of antioxidants, inhibition of oxidative DNA damage, protein modification, and cell proliferation, and induction of apoptosis. However EAF rich in constituent phytochemicals was more effective than MF in modulating multiple molecular targets. These results provide evidence for the chemopreventive efficacy of neem leaf fractions in the rat mammary tumour model.     

Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden.