Amelioration of alcohol-induced oxidative stress by Emblica officinalis (amla) in rats

The present study was aimed at investigating the ameliorative effect of Emblica (Phyllanthus Emblica L) fruit extract (EFE) against alcohol-induced oxidative changes in plasma biochemical profile in rats. Alcohol administration (5 g/kg body wt/day) for 60 days resulted in significantly (P<0.05) higher levels of plasma nitrite/nitrate (NOx), total bilirubin, creatinine, and abnormalities in lipid and lipoproteins. Moreover, alcohol receiving rats showed significantly (P<0.05) lowered plasma total protein, albumin/globulin (A/G) ratio and uric acid, with no significant change in glucose level. The EFE administration (250 mg/kg body wt/day) to alcohol-administered rats significantly modulated plasma lipids and lipoprotein patterns and also decreased nitrite/nitrate, total bilirubin and creatinine levels. EFE administration to alcohol receiving rats showed a significant (P<0.05) increase in plasma total protein, A/G ratio and uric acid levels. Total cholesterol (r = 0.466), triglycerides (r = 0.574), VLDL-C (r = 0.578), LDL-C (r = 0.225) and total bilirubin (r = 0.419) showed a stronger positive correlation with that of NOx in alcohol-treated rats. The concentration of nitric oxide (NOx) was negatively correlated with HDL-C (r = -0.285) and uric acid (r = 0.392) in alcohol-treated rats. The amelioration of alcohol-induced oxidative stress might be due to the combined effect of phytophenols, such as tannins and flavonoid compounds and vitamin C.     

Effects of L-carnitine on neutrophil-mediated ischemia-reperfusion injury in rat stomach

Reactive oxygen metabolites play an important role in ischemia-reperfusion related gastric injury. Primary sources of reactive oxygen metabolites seem to be the xanthine/xanthine oxidase system and neutrophils accumulating within the reperfused tissue. Tissue myeloperoxidase activity is an important index of neutrophil accumulation. The purpose of the present study was to clarify the effect of L-carnitine on the accumulation of neutrophils and neutrophil-induced gastric mucosal damage in rats exposed to ischemia-reperfusion. Rats were randomly divided into three groups: sham-operated, ischemia-reperfusion and ischemia-reperfusion plus L-carnitine groups. Ischemia was induced by clamping the celiac artery for 30 min and then reperfusion was established for 60 min. Gastric injury was assessed by measuring myeloperoxidase activity in gastric tissue. The neutrophil accumulation and hemorrhagic lesions due to ischemia-reperfusion in gastric mucosa were ascertained in a histological study. L-Carnitine (100 mg kg(-1)) administrated intravenously 5 min before ischemia significantly reduced both the gastric injury and myeloperoxidase activity compared with the ischemia-reperfusion group. The results suggest that L-carnitine provides marked protection against ischemia-reperfusion-related gastric injury which could be due to its ability to reduce neutrophil accumulation in ischemic tissue.     

氧自由基在应激性胃溃疡中的发病学意义

本工作研究了氧自由基在大鼠冷冻束缚应激性胃溃疡中的发病学意义。实验结果如下:(1)以超氧自由基清除剂超氧化物歧化酶(SOD)或羟自由基清除剂二甲亚砜和甘露醇预先处理大鼠,均可显著地减轻胃粘膜损伤;(2)应激时,胃粘膜内的脂质过氧化分解产物丙二醛的含量显著升高;(3)组织化学的研究显示,胃粘膜层含有丰富的黄嘌呤氧化酶,其活性在应激时明显升高,预先用别嘌呤醇处理大鼠以抑制黄嘌呤氧化酶的活性,可使胃粘膜损伤显著减轻。上述结果提示,氧自由基是应激性胃溃疡的重要致病因子,而黄嘌呤氧化酶活性的升高似可能为应激时氧自由基生成增加的重要原因。     

Dehydrogenase conversion to oxidase and lipid peroxidation in brain after carbon monoxide poisoning.

The conversion of xanthine dehydrogenase to xanthine oxidase and lipid peroxidation were measured in brain from carbon monoxide- (CO) poisoned rats. Sulfhydryl-irreversible xanthine oxidase increased from a control level of 15% to a peak of 36% over the 90 min after CO poisoning, while the conjugated diene level doubled. Reversible xanthine oxidase was 3-6% of the total enzyme activity over this span of time but increased to 31% between 90 and 120 min after poisoning. Overall, reversible and irreversible xanthine oxidase represented 66% of total enzyme activity at 120 min after poisoning. Rats depleted of this enzyme by a tungsten diet and those treated with allopurinol before CO poisoning to inhibit enzyme activity exhibited no lipid peroxidation. Treatment immediately after poisoning with superoxide dismutase or deferoxamine inhibited lipid peroxidation but had no effect on irreversible oxidase formation. Biochemical changes only occurred after removal from CO, and changes could be delayed for hours by continuous exposure to 1,000 ppm CO. These results are consistent with the view that CO-mediated brain injury is a type of postischemic reperfusion phenomenon and indicate that xanthine oxidase-derived reactive oxygen species are responsible for lipid peroxidation.     

Capsaicin protects against ethanol-induced oxidative injury in the gastric mucosa of rats

In this study, we investigated the protective effects of capsaicin on gastric mucosal oxidative damage induced by ethanol. Sprague Dawley rats intragastrically received 0.5-10 mg/kg, BW capsaicin or vehicle; 30 min later gastric lesions were induced by intragastric administration of absolute ethanol. Lipid peroxidation was estimated by measuring thiobarbituric acid reactive substances in gastric mucosa. Myeloperoxidase activity, a marker enzyme of polymorphonuclear leukocytes for tissue inflammation, was also measured in the gastric mucosa. The expression level of cyclooxygenase-2, which increases in inflammatory region, was determined by Western blot analysis. Capsaicin significantly suppressed gastric haemorrhagic erosions induced by ethanol. Capsaicin inhibited lipid peroxidation and myeloperoxidase activity in ethanol-induced gastric mucosal lesion in a dose-dependent manner. Capsaicin also inhibited the expression of cyclooxygenase-2 in the gastric mucosal lesion. The gastroprotective activity of capsaicin on the ethanol-induced oxidative damage may be important for chemoprevention.     

Salicylic acid blocks indomethacin-induced cyclooxygenase inhibition and lesion formation in rat gastric mucosa

Salicylic acid has been shown to decrease gastric mucosal lesions induced by indomethacin in the rat. In vitro, it has also been shown to counteract the inhibitory effect of indomethacin and aspirin on the cyclooxygenase enzyme system in seminal vesicle microsomes and in platelets and vascular tissue. The hypothesis that the mechanism of salicylic acid "protection" against indomethacin-induced gastric lesions involves interference with indomethacin-induced mucosal cyclooxygenase inhibition was tested. Male, fasted rats were treated with intragastric salicylic acid in doses of 50, 100, 200, 300, or 400 mg/kg concomitantly with a sc injection of 20 mg/kg of indomethacin. Gastric mucosal lesions and mucosal cyclooxygenase activity (as measured by ex vivo prostaglandin F2 alpha synthesis) were examined 3 hr later. Intragastric salicylic acid, 200-400 mg/kg, significantly reduced indomethacin-induced lesion formation, while counteracting significantly indomethacin inhibition of prostaglandin synthesis. Salicylic acid alone did not significantly change cyclooxygenase activity. It is concluded that topical salicylic acid can decrease indomethacin-induced gastric mucosal lesion in the rat, in part, by counteracting the inhibitory effect of indomethacin at the cyclooxygenase level.     

Curative effect of selenium against indomethacin-induced gastric ulcers in rats

Indomethacin is a nonsteroid anti-inflammatory agent that is known to induce severe gastric mucosal lesions. In this study, we investigated the effect of selenium on gastric mucosal lesions in rats. To confirm the curative effect of selenium against indomethacin-induced gastric ulcers, gastric ulcers were induced by oral administration of 25 mg/kg indomethacin, and then different doses (10, 50, and 100 microgram/kg of body weight) of selenium or vehicle were treated by oral gavage for 3 days. Oral administration of indomethacin clearly increased the gastric ulcer area in the stomach, whereas selenium applied for 3 days significantly decreased the gastric ulcer area in a dose-dependent manner. In addition, selenium markedly reduced the increase of lipid peroxidation induced by indomethacin in the gastric mucosa and increased activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner. These results reveal that selenium can heal indomethacininduced gastric ulcers through elimination of the lipid peroxides and activation of radical scavenging enzymes.     

Attenuation of potassium bromate-induced nephrotoxicity by coumarin (1,2-benzopyrone) in Wistar rats: chemoprevention against free radical-mediated renal oxidative stress and tumor promotion response

We report the modulatory effect of coumarin (1,2-benzopyrone) on potassium bromate (KBrO(3)) mediated nephrotoxicity in Wistar rats. KBrO(3) (125 mg/kg body weight, i.p.) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H(2)O(2)) generation with reduction in renal glutathione content and antioxidant enzymes. It also enhances blood urea nitrogen, serum creatinine, ornithine decarboxylase (ODC) activity and [(3)H]-thymidine incorporation into renal DNA. Treatment of rats orally with coumarin (10 mg/kg body weight and 20 mg/kg body weight) resulted in a significant decrease in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H(2)O(2) generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01) and antioxidant enzymes were also recovered to significant level (P < 0.001). These results show that coumarin may be used as an effective chemopreventive agent against KBrO(3)-mediated renal oxidative stress, toxicity and tumor promotion response in Wistar rats.     

Attenuation of oxidative stress, inflammation and early markers of tumor promotion by caffeic acid in Fe-NTA exposed kidneys of Wistar rats

Iron nitrilotriacetate (Fe-NTA), a chief environmental pollutant, is known for its extensive toxic manifestations on renal system. In the present study, caffeic acid, one of the most frequently occurring phenolic acids in fruits, grains, and dietary supplements was evaluated for its shielding effect against the Fe-NTA-induced oxidative, inflammatory, and pathological damage in kidney. Fe-NTA was administered (9 mg Fe/kg body weight) intraperitoneally to the Wistar male rats on 20th day while caffeic acid was administered orally (20 and 40 mg/kg body weight) before administration of Fe-NTA. The intraperitoneal administration of Fe-NTA-enhanced lipid peroxidation, xanthine oxidase, and hydrogen peroxide generation with reduction in renal glutathione content, antioxidant enzymes, viz., catalase, glutathione peroxidase, and glutathione reductase. A sharp elevation in the levels of myloperoxidase, blood urea nitrogen (BUN), and serum creatinine has also been observed. Tumor promotion markers viz., ornithine decarboxylase (ODC) and [(3)H] thymidine incorporation into renal DNA were also significantly increased. Treatment of rats orally with caffeic acid (20 and 40 mg/kg body weight) resulted in a significant decrease in xanthine oxidase (P < 0.001), lipid peroxidation (P < 0.001), γ-glutamyl transpeptidase (P < 0.01), and H(2)O(2) (P < 0.01). There was significant recovery of renal glutathione content (P < 0.001) and antioxidant enzymes (P < 0.001). There was also a reversal in the enhancement of renal ODC activity, DNA synthesis, BUN, and serum creatinine (P < 0.001). All these changes were supported by histological observations. The results indicate that caffeic acid may be beneficial in ameliorating the Fe-NTA-induced oxidative damage and tumor promotion in the kidney of rats.     

Preventive effect of tannic acid on 2-acetylaminofluorene induced antioxidant level, tumor promotion and hepatotoxicity: a chemopreventive study

Tannic acid, present in almost every food derived from plants, has been widely investigated as a chemopreventive agent because, apart from its use as a food additive, pharmacological studies have demonstrated its many health-promoting properties. In this study, we show the modulatory effect of tannic acid on 2-acetylaminofluorene (2-AAF)-mediated hepatic oxidative stress and cell proliferation in rats. 2-AAF (50 mg/kg body weight) caused reduction in hepatic glutathione content and the activities of hepatic anti-oxidant enzymes and phase-II metabolizing enzymes with an enhancement of xanthine oxidase activity, lipid peroxidation and hydrogen peroxide content. 2-AAF treatment also induced serum oxaloacetate and pyruvate transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase. Treatment of rats orally with tannic acid (125 and 250 mg/kg body weight) resulted in significant recovery of hepatic glutathione content, antioxidant and phase-II metabolizing enzymes. Also, significant decreases in lipid peroxidation, xanthine oxidase, hydrogen peroxide generation and liver damage marker enzymes were observed. The antiproliferative efficacy of the tannic acid was also evaluated. The promotion parameters induced (ornithine decarboxylase activity and DNA synthesis) by 2-AAF administration in the diet with partial hepatectomy (PH) were also significantly suppressed, dose dependently, by tannic acid. Hence, we propose that tannic acid might suppress the promotion stage via inhibition of oxidative stress and polyamine biosynthetic pathway.     

Inhibition of potassium bromate-induced renal oxidative stress and hyperproliferative response by Nymphaea alba in Wistar rats

KBrO3-mediated renal injury and hyperproliferative response in Wistar rats. In this communication, we report the efficacy of Nymphaea alba on KBrO3 (125 mg/kg body weight, intraperitoneally) caused reduction in renal glutathione content, renal antioxidant enzymes and phase-II metabolising enzymes with enhancement in xanthine oxidase, lipid peroxidation, gamma-glutamyl transpeptidase and hydrogen peroxide (H202). It also induced blood urea nitrogen, serum creatinine and tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and DNA synthesis. Treatment of rats with Nymphaea alba (100 and 200 mg/kg body weight) one hour before KBrO3 (125 mg/kg body weight, i.p.) resulted in significant decreases in xanthine oxidase (P < 0.05), lipid peroxidation, gamma-glutamyl transpeptidase, H202 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content, glutathione metabolizing enzymes and antioxidant enzymes were also recovered to significant levels (P < 0.001). These results show that Nymphaea alba acts as chemopreventive agent against KBrO3-mediated renal injury and hyperproliferative response.     

Suppressive effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant on ethanol-induced gastric mucosal injury in rats

Ethanol has been found to induce ulcerative gastric lesion in humans. The present study investigated the in vivo protective effect of astaxanthin isolated from the Xanthophyllomyces dendrorhous mutant against ethanol-induced gastric mucosal injury in rats. The rats were treated with 80% ethanol for 3 d after pretreatment with two doses of astaxanthin (5 and 25 mg/kg of body weight respectively) for 3 d, while the control rats received only 80% ethanol for 3 d. The oral administration of astaxanthin (5 and 25 mg/kg of body weight) showed significant protection against ethanol-induced gastric lesion and inhibited elevation of the lipid peroxide level in gastric mucosa. In addition, pretreatment with astaxanthin resulted in a significant increase in the activities of radical scavenging enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. A histologic examination clearly indicated that the acute gastric mucosal lesion induced by ethanol nearly disappeared after pretreatment with astaxanthin.     

The role of aldehyde oxidase in ethanol-induced hepatic lipid peroxidation in the rat.

Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.     

Protective effects of ascorbic acid, Dl-α-tocopherol acetate, and sodium selenate on ethanol-induced gastric mucosal injury of rats

In this study, the effect of ascorbic acid (vitamin C), Dl-α-tocopherol acetate (vitamin E), and sodium selenate (selenium) on ethanol-induced gastric mucosal injury in rats was investigated morphologically and biochemically. The gastric mucosal injury was produced by administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/kg), vitamin E (250 mg/kg), and selenium (0.5 mg/kg) for 3 d 1 h prior to the administration of absolute ethanol. In gastric mucosa of rats given ethanol according to control groups, neuronal nitric oxide expression decreased. This immunoreactivity was much lower in the group given ethanol+vitamin C+vitamin E+selenium than the control group and the ethanol-induced group. Scanning electron microscopic evaluation of the ethanol-induced group, when compared to control groups, revealed degenerative changes in gastric mucosa, whereas a good arrangement in surface topography of gastric mucosa in the group given ethanol + vitamin C+vitamin E + selenium was observed. In the group administered ethanol, a reduction of the stomach glutathione (GSH) and serum total protein levels and increases in serum sialic acid, triglycerides, and stomach lipid peroxidation (LPO) levels were observed. Vitamin C+vitamin E+Se administration to alcohol-treated rats significantly increased the serum total protein, triglyceride levels, and stomach GSH levels and significantly lowered the levels of serum sialic acid and stomach LPO compared to untreated alcohol-supplemented rats. As a result of these findings, we can say that the combination of vitamin C, vitamin E, and selenium has a protective effect on ethanol-induced gastric mucosal injury of rats.     

Cytoprotective effect of copper(II) complexes against ethanol-induced damage to rat gastric mucosa.

The cytoprotective effect of various copper(II) complexes on the gastric mucosa damage induced by acute intragastric administration of ethanol was investigated. For in vitro experiments, the following copper(II) complexes were tested: Cu(II)(L-Trp)(L-Phe), Cu(II)(L-Leu)Cu(II)(L-Leu-Leu)(L-Leu), Cu(II)(L-Phe-L-Leu), Cu(II)(Gly-His-Lys), and Cu(II)(cyHis)2(ClO4)2. Inorganic copper such as CuSO4 was also tested. The free radical generating system, acting for 2 hr on cardial and fundic mucosa scrapings or mucosal microsomes, was Fe++ (20 microM)/ascorbate (0.25 mM). We found a marked inhibition to 75% of lipid peroxidation in the range 10-100 mM, regardless of whether copper was given in complexed or inorganic form. The results suggest that nontoxic copper(II)-amino acid complexes are able to neutralize oxygen-derived free radicals. In addition, copper(II) complexes suppressed membrane lipid peroxidation when mucosa homogenates were exposed to t-butyl hydroperoxide (1-20 microM) plus Fe++ (50 microM). In vivo experiments on rat stomachs, pretreated p.o. by gavage either with Cu(II)(L-Trp)(L-Phe) as paradigmatic agent or with copper sulphate at equivalent doses in the range 3-30 mg/kg body weight showed a significant decrease (30 min after 95% ethanol administration) in the number and severity of mucosal hemorrhagic lesions. In the gastric mucosa scrapings of copper-treated rats after ethanol exposure, we found that malondialdehyde and conjugated diene levels were unchanged compared to those of untreated controls; five enzyme activities released from lysosomes were near control values. In isolated mucosal cells, whether or not pretreated with 200 microM solution of either Cu(II)(L-Trp)(L-Phe) or CuSO4, the release of cathepsin D activity was also unmodified. The results suggest that the cytoprotective effect of Cu(II) complexes against ethanol-induced mucosal lesions was not associated in vivo to lipid peroxidation.     

Effect of alterations in membrane lipid unsaturation on the properties of the insulin receptor of Ehrlich ascites cells

Rat heart ornithine decarboxylate activity from isoproterenol-treated rats was inactivated in vitro by reactive species of oxygen generated by the reaction xanthine/xanthine oxidase. Reduced glutathione, dithiothreitol and superoxide dismutase has a protective effect in homogenates and in partially purified ornithine decarboxylase exposed to the xanthine/xanthine oxidase reaction, while diethyldithiocarbamate, which is an inhibitor of superoxide dismutase, potentiated the damage induced by O2- on enzyme activity. Dithiothreitol at concentrations above 1.25 mM had an inhibitory effect upon supernatant ornithine decarboxylase activity, while at 2.5 mM it was most effective in the recovery of ornithine decarboxylase activity, after the purification of the enzyme by the ammonium sulphate precipitation procedure. The ornithine decarboxylase inactivated by the xanthine/xanthine oxidase reaction showed a higher value of Km and a reduction of Vmax with respect to control activity. The exposure of rats to 100% oxygen for 3 h reduced significantly the isoproterenol-induced heart ornithine decarboxylase activity. The injection with diethyldithiocarbamate 1 h before hyperoxic exposure further reduced heart ornithine decarboxylase activity.     

Superoxide radicals scavenging and xanthine oxidase inhibitory activity of magnesium lithospermate B from Salvia miltiorrhiza

In this study we investigated the superoxide radicals scavenging effect and xanthine oxidase inhibitory activity by magnesium lithospermate B, which was originally isolated from the roots of Salvia miltiorrhiza (also named Danshen or Dansham), an important herb in Oriental medicine. Superoxide radicals were generated both in beta-NADH/PMS system and xanthine/ xanthine oxidase system. Magnesium lithospermate B significantly inhibited the reduction of NBT induced by superoxide radicals with an IC(50) of 29.8 microg/mL and 4.06 microg/mL respectively in the two systems. Further study suggested that magnesium lithospermate B can directly inhibit xanthine oxidase and exhibits competitive inhibition. Magnesium lithospermate B was also found to have the hypouricemic activity in vivo against potassium oxonate-induced hyperuricaemia in mice. After oral administration of magnesium lithospermate B at doses of 10, 20 and 30 mg/kg, there was a significant decrease in the serum urate level when compared to the hyperuricemia control. In addition, magnesium lithospermate B significantly protected HL-60 cells from superoxide radicals-induced apoptosis in the xanthine/ xanthine oxidase reactions. This study provided evidence that magnesium lithospermate B exhibits direct superoxide radicals scavenging and xanthine oxidase inhibitory activity.     

Induction of renal oxidative stress and cell proliferation response by ferric nitrilotriacetate (Fe-NTA): diminution by soy isoflavones

Ferric nitrilotriacetate (Fe-NTA) is a known potent nephrotoxic agent. In this communication, we report the chemopreventive effect of soy isoflavones on renal oxidative stress, toxicity and cell proliferation response in Wistar rats. Fe-NTA (9 mg Fe/kg body weight, intraperitoneally) enhances gamma-glutamyl transpeptidase, renal lipid peroxidation, xanthine oxidase and hydrogen peroxide (H2O2) generation with reduction in renal glutathione content, antioxidant enzymes, viz., glutathione peroxidase, glutathione reductase, catalase, glucose-6-phosphate dehydrogenase and phase-II metabolising enzymes such as glutathione-S-transferase and quinone reductase. Fe-NTA treatment also induced tumor promotion markers, viz., ornithine decarboxylase (ODC) activity and thymidine [3H] incorporation into renal DNA. A sharp elevation in the levels of blood urea nitrogen and serum creatinine has also been observed. Treatment of rats orally with soy isoflavones (5 mg/kg body weight and 10 mg/kg body weight) resulted in significant decreases in gamma-glutamyl transpeptidase, lipid peroxidation, xanthine oxidase, H2O2 generation, blood urea nitrogen, serum creatinine, renal ODC activity and DNA synthesis (P < 0.001). Renal glutathione content (P < 0.01), glutathione metabolizing enzymes (P < 0.001) and antioxidant enzymes were also returned to normal levels (P < 0.001). Thus, our data suggest that soy isoflavones may be used as an effective chemopreventive agent against Fe-NTA-mediated renal oxidative stress, toxicity and cell proliferation response in Wistar rats.     

Protection by tetramethylpyrazine in acute absolute ethanol-induced gastric lesions

Acute oral administration of absolute ethanol (1.0 ml/kg) to fasting rats produced extensive necrosis of the gastric mucosa within 1 h. Pretreatment 30 min before administration of ethanol with oral tetramethylpyrazine (TMP) prevented this necrosis. Gross examination of the gastric mucosa of rats that received TMP showed fewer gastric lesions than that of rats who did not receive TMP. TMP pretreatment in rats exhibited superoxide scavenging activity in absolute ethanol-induced lipid peroxidation in gastric mucosal homogenates. TMP added in vitro to gastric homogenates made from control rats also showed scavenging activity. We conclude that the gastric protective mechanism of TMP could be attributed, at least in part, to its ability to inhibit lipid peroxidation and hence indirectly protect the gastric mucosa from oxidative stress.     

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid.

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.