Anti-ulceral and anti-oxidative properties of "earthworm paste" of Lampito mauritii (Kinberg) on Rattus Norvegicus

Studies have been made to understand the anti-ulceral and anti-oxidant properties of the "earthworm paste" derived from Lampito mauritii (Kinberg), an indigenous species, in comparison with the standard anti-ulceral drug-ranitidine, on the Wistar strain albino rats Rattus norvegicus. Administration of 200 mg/kg aspirin was found to increase the volume of gastric juice secretion, total acidity, free acidity, ulcer index and reduce the pH. It also had decreased the anti-oxidant levels such as reduced glutathione, glutathione peroxidase, catalase, superoxide dismutase and increased the level of thiobarbituric acid reactive substances. Pretreatment with the standard drug-ranitidine (50 mg/kg) and different doses of "earthworm paste" (20, 40, 80, 160 and 320 mg/kg) in ulcer induced animal had enhanced the pH, decreased the volume of gastric juice, free acidity, total acidity and reduced the ulcer index. Further the activities of reduced glutathione, glutathione peroxidase, catalase, superoxide dismutase were increased whereas the thiobarbituric acid reactive substance had decreased. The results were more significant in rats administered with 160 mg/kg "earthworm paste" than the application of ranitidine and other doses of "earthworm paste". This indicates the presence of antiulcer and anti-oxidative effects in "earthworm paste". In conclusion, administration of 160 mg "earthworm paste"/kg was found to have better therapeutic properties.     

Earthworm paste (Lampito mauritii, Kinberg) alters inflammatory, oxidative, haematological and serum biochemical indices of inflamed rat

Experiments were conducted to understand the therapeutic properties such as anti-inflammatory, anti-oxidative, haematological and serum biochemical markers of earthworm paste (EP) derived from an indigenous species Lampito mauritii (Kinberg), in comparison with the standard anti-inflammatory drug- aspirin, on Wistar albino rat (Rattus norvegicus). Administration of earthworm paste of Lampito mauritii at the rate of 80 mg/kg into albino rats which were induced of inflammation, was found to reduce inflammation, restore the levels of antioxidants-reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase and thiobarbituric acid reactive substances, normalise the values of erythrocyte, leukocyte, differential levels of neutrophils, lymphocytes, eosinophils, haemoglobin and serum biochemical contents e.g., protein, albumin, glucose, cholesterol, acid and alkaline phosphatase, electrolytes e.g., sodium, potassium and chloride. The anti-inflammatory activity together with antioxidant property of EP seems to be due to the high polyphenolic content of earthworm tissue.     

Effect of Azadirachta indica (Neem) leaf aqueous extract on paracetamol-induced liver damage in rats

The effect of aqueous leaf extract of Azadirachta indica (A. indica) was evaluated in paracetamol induced hepatotoxicity in rats. Liver necrosis was produced by administering single dose of paracetamol (2 g/kg, p.o.). The liver damage was evidenced by elevated levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transpeptidase (gamma-GT) and by histopathological observations of liver sections. Aqueous A. indica leaf extract (500 mg/kg, p.o.) significantly (P < 0.01) reduced these elevated levels of AST, ALT and gamma-GT. Paracetamol induced liver necrosis was also found to be reduced as observed macroscopically and histologically.     

Effect of old age on paracetamol-induced lipid peroxidation in rat liver

Post-mitochondrial supernatants isolated from the livers of mature rats (3 to 6 months old) 2 h or more after the administration of a single large oral dose of paracetamol (800 mg/kg) showed rapid rates of lipid peroxidation when incubated in vitro. In similar experiments with old rats (27-30 months old) the time between administration of paracetamol and the onset of lipid peroxidation was much longer (6 h or more). In both age groups, lipid peroxidation was dependent on the depletion of glutathione from the liver.     

Repair of rat liver DNA in vivo damaged by ethylene dibromide.

Tube feeding of [¹⁴C]Jethylene dibromide (EDB) to non-fasted rats resulted in the incorporation of the radioactivity into liver DNA, RNA and protein. Using alkaline and neutral sucrose gradients, it was observed that administration of the pesticide to non-fasted rat caused slower sedimentation of liver DNA in alkaline and not in neutral sucrose gradients. Slower sedimentation of liver DNA in alkaline sucrose gradients was apparent within 2 hr after the administration of a dose of 22 mg/100 g or 4 hr after a dose of 7.5 mg/100 g of body weight. Using a dose of 7.5 mg/100 g, the EDB-induced liver DNA damage was repaired significantly by 17.5 hr and almost completely by 96 hr. Administration of diethyldithiocarbamate, a free radical scavenger, did not inhibit liver DNA damage caused by EDB.     

羧甲基壳聚糖对D-半乳糖诱导氧化损伤模型小鼠肝、脑的保护作用

目的:探索羧甲基壳聚糖(CMC)对D-半乳糖诱导氧化损伤模型小鼠肝、脑的作用。方法:实验分为4组:对照组、CMC组、D-半乳糖模型组、D-半乳糖+CMC组。测定各组小鼠肝、脑超氧化物歧化酶(SOD)、过氧化氢酶(CAT)的活性、丙二醛(MDA)的含量及蛋白质羰基化程度。结果:D-半乳糖可诱导小鼠蛋白质羰基化,诱导小鼠氧化损伤,CMC可使小鼠蛋白质羰基化含量降低,SOD、CAT活性增加,MDA含量降低。结论:CMC对D-半乳糖引起的氧化损伤有一定的保护作用。     

银杏提取物对过氧化氢损伤的培养大鼠心肌细胞的保护作用

目的:探讨银杏叶提取物(GbE)对过氧化氢损伤的培养心肌细胞的保护作用及其机制。方法:比色法测定乳酸脱氢酶活性;戊巴比妥酸法测定细胞内脂质过氧化物含量;透射电镜下观察细胞超微结构。结果:过氧化氢导致心肌细胞LDH释放从(2166±247)U·L~(-1)增至(5180±648)U·L~(-1),MDA含量从每10~6细胞(3.5±0.2)nmol增至(7.2±0.4)nmol;心肌细胞超微结构受到严重损伤。加GbE使LDH释放从(5180±648)U·L~(-1)降至(3496±386)U·L~(-1);MDA生成由每10~6细胞(7.2±0.4)nmol降至(4.8±0.9)nmol并减轻心肌超微结构的损伤。结论:GbE通过清除氧自由基保护过氧化氢损伤的心肌细胞。     

二苯甲酰甲烷对对乙酰氨基酚所致MT(-/-)小鼠急性肝损伤的保护作用

目的探讨二苯甲酰甲烷(DBM)对对乙酰氨基酚所致MT(-/-)小鼠急性肝损伤的保护作用。方法采用对乙酰氨基酚(450mg·kg-1,sc)所致小鼠急性肝损伤模型。雌性MT(-/-)小鼠随机分为5组,对照组、模型组、DBM50,100和200mg·kg-1组。DBM组分别igDBM50,100和200mg·kg-1·d-1,共4d。第4天给药后30min,模型组和DBM组小鼠sc对乙酰氨基酚造模。24h后,测定血清中谷丙转氨酶(GPT)、谷草转氨酶(GOT)和乳酸脱氢酶(LDH)的活性。制备肝匀浆,测定肝中还原型谷胱甘肽(GSH)、氧化型谷胱甘肽(GSSG)和丙二醛(MDA)的含量;留取肝脏组织,常规石蜡包埋切片,HE染色,光镜观察肝脏组织病理变化。结果与模型组相比,各DBM组小鼠血清中GPT,GOT和LDH活性显著降低;GSH/GSSG比值升高,MDA含量下降;肝脏组织病理损伤明显减轻。结论DBM对对乙酰氨基酚引起的MT(-/-)小鼠急性肝损伤具有明显的保护作用。     

银杏提取物对过氧化氢损伤的培养大鼠心肌细胞的保护作用

探讨银杏叶提取物对过氧化氢损伤的培养心肌细胞的保护作用及其机制。方法；比色法测定乳酸脱氢酶活性；戊巴比妥酸法测定细胞内质质过氧化物含量；透射电镜下观察细胞超微结构。结果：过氧化氢导致心肌细胞ＬＤＨ释放从（２１６６±２４７）Ｕ．Ｌ＾－１增至（５１８０±６４８）Ｕ．Ｌ＾－１ＭＤＡ含量从每１０＾６细胞９３．５±０．２）ｎｍｏｌ增至（７．２±０．４）ｎｍｏｌ；．心肌细胞超微结构受到严重损伤。     

Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes,oxidative stress,impaired liver and kidney functions and haematotoxicity in rat

The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.     

D-Dopachrome tautomerase is a candidate for key proteins to protect the rat liver damaged by carbon tetrachloride

Carbon tetrachloride (CCl4) is known to induce liver damage. Animal experiments with CCl4 injections have revealed many findings, especially mechanisms of liver damage and liver regeneration. Recently, proteomic approaches have been introduced in various studies to evaluate the quantitative and qualitative changes in the comprehensive proteome level. The aim of this research is to elucidate the key protein for liver damage, liver protection and liver regeneration by using proteomic techniques. 50 % (v/v) CCl4 in corn oil was administered intraperitoneally to adult male rats at a dose of 4ml/kg body weight. Approximately 24h after the injection, the liver was removed and extracted proteins were analyzed with cleavable isotope coded affinity tag (cICAT) reagents, two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). A twelvefold increase in D-dopachrome tautomerase (DDT) was indicated. This enzyme has been reported to be involved in the biosynthesis of melanin, an antioxidant. According to the histological analysis, melanin levels were increased in un-damaged hepatocytes of CCl4-treated rats. These results suggest that the increase in DDT is a response to liver damage, accelerates melanin biosynthesis and protects the liver from oxidative stress induced by CCl4.     

Inhibition of glycosaminoglycan synthesis in anatomically intact rat patellar cartilage by paracetamol-induced serum sulfate depletion

We have studied the effect of low sulfate concentrations on the glycosaminoglycan synthesis in rat patellar cartilage in vivo as well as in vitro. The oral administration of 200 mg/kg paracetamol to male Wistar rats resulted in a significant reduction of the serum sulfate concentration. Reduced serum sulfate availability resulted in a 34% decrease of glycosaminoglycan synthesis in patellar cartilage. This is due to sulfate depletion since paracetamol had no direct effects on glycosaminoglycan synthesis and a slight but significant inhibitory effect on the catabolism of radiolabeled glycosaminoglycans in vitro. The glycosaminoglycans synthesized at low sulfate concentrations in vivo were similar to the glycosaminoglycans synthesized at physiological sulfate concentrations. Studying the effect of sulfate availability in vitro on glycosaminoglycan synthesis in patellar cartilage we found that incubation of rat patellae in medium containing less than 0.5 mM inorganic sulfate led to a decreased sulfate incorporation. The use of potential sulfate decreasing drugs can lead to inhibition of glycosaminoglycan synthesis. This argues for a reconsideration of the use of these drugs in patients with already dysfunctioning cartilage metabolism as in rheumatoid arthritis and osteoarthrosis.     

Liver antioxidant capacity in the early phase of acute paracetamol-induced liver injury in mice

The aim of our study was to investigate the relationship between liver antioxidant capacity and hepatic injury in the early phase of acute paracetamol intoxication in mice. Male Swiss mice were divided into groups: (1) control, that received saline, (2) paracetamol-treated group (300 mg/kg intraperitoneally). Animals were sacrificed 6, 24 and 48 h after treatment. Oxidative stress parameters were determined in blood and liver samples spectrophotometrically. Liver malondialdehyde and nitrite + nitrate level were significantly increased 6 h after paracetamol administration in comparison with control group (p < 0.05). Paracetamol induced a significant reduction in total liver superoxide dismutase (SOD) and copper/zinc SOD activity at all time intervals (p < 0.01). However, manganese SOD activity was significantly increased within 6 h (p < 0.01), while its activity progressively declined 24 and 48 h after paracetamol administration in comparison with control group (p < 0.01). Content of sulfhydryl groups in the liver was increased 24 h after paracetamol administration (p < 0.05), while its level was decreased within next 24 h when compared to control animals (p < 0.01). Our data showed that liver antioxidant capacity increases in first 24 h of paracetamol-induced liver injury were in correlation with manganese SOD activity and increase in level of sulfhydryl groups.     

Chemoprevention of N-nitrosodiethylamine induced phenobarbitol promoted liver tumors in rat by extract of Indigofera aspalathoides

The chemopreventive effect of ethanol extract of Indigofera aspalathoides (EIA) on N-nitrosodiethylamine (DEN, 200 mg/kg)-induced experimental liver tumor was investigated in male Wistar rats. Oral administration of ethanol extract of Indigofera aspalathoides (250 mg/kg) effectively suppressed liver tumor induced with DEN as revealed by decrease in the levels of extend of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), total bilirubin, gamma glutamate transpeptidase (GGTP), lipid peroxidase (LPO), glutathione peroxidase (Gpx) and glutathione S-transferase (GST) with a concomitant increase in enzymatic antioxidant (superoxide dismutase and catalase) levels when compared to those in liver tumor bearing rats. The histopathological changes of liver sample were compared with respective control. Our results show a significant chemopreventive effect of EIA against DEN induced liver tumor.     

Metabolism of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes.

1. The metabolic dispositions of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes have been investigated, and the results compared. 2. The drug was well absorbed after oral administration to rats and was widely distributed in all tissues, which, with the exception of brain, had higher concentrations of the drug, its metabolites, or both, than did plasma. 3. Metabolism by rat-liver microsomes included N-oxidation, N-demethylation, S-oxidation and aryl hydroxylation. Metabolites hydroxylated in the aromatic ring were excreted only in bile, both by the isolated perfused rat livers and by anaesthetized bile-duct-cannulated rats. 4. Liver perfusion of the benzothiazine or its monodesmethyl analogue (V) resulted in temporary cessation of the flow of perfusate through the organ. The benzothiazine sulphoxide (IV) had only a slight effect on the flow of liver perfusate, but IV followed by I caused the flow of perfusate to cease.