Carbon tetrachloride-induced liver injury in the rabbit.

CCl4 administration to rabbits leads to early destruction of liver microsomal cytochrome P-450, to depression of glucose 6 phosphatase, to ultrastructurally revealable alterations and to an intense necrosis and fat accumulation in liver. Despite the known resistance of rabbit liver microsomes to lipid peroxidation, CCl4 administration to rabbits promoted lipid peroxidation of their liver microsomal lipids as revealable by the diene hyperconjugation technique, at periods of time from 1 to 12 h. Nevertheless, the intensity of this process is not equivalent to that occurring in rat liver microsomes, since the arachidonic acid content of rabbit liver microsomal lipids does not decrease at either 6 or 24 h after CCl4 administration. Rabbit liver is able to activate CCl4 to reactive metabolites that bind covalently to lipids. Relevance of covalent binding of CCl4 reactive metabolites and CCl4-promoted lipid peroxidation to CCl4-induced rabbit liver injury is analysed.     

Prevention of carbon tetrachloride-induced liver necrosis by several amino acids.

Aspartic acid, cystine, methionine and tyrosine were protective against carbon tetrachloride (CCl4)-induced liver necrosis 24 h after its administration, when given 30 min before the hepatotoxin. Aspartic acid, cystine and tyrosine were also effective when given as late as 6 h after CCl4. The protective effects of these amino acids, however, were no longer evident when observations of CCl4-induced necrosis were made at 72 h, except for cystine, which retained its protective potential. Protective amino acid administration did not modify the concentration of CCl4 in liver, nor did it decrease the intensity of the covalent binding of CCl4 reactive metabolites to cellular constituents or the CCl4-induced lipid peroxidation. Consequently, protection cannot be attributed to modulation of these parameters. Cystine, tyrosine and aspartic acid significantly lowered body temperature of the CCl4-treated rats, while methionine did not. Combined, these results suggest that the protective effect is not attributable to lowering of body temperature in CCl4-treated animals. Protection probably results from changes in the cell response to injury promoted by amino acid administration.     

Prevention of carbon tetrachloride-induced liver necrosis by the chelator alizarin sodium sulfonate.

The administration of the calcium chelator alizarin sodium sulfonate (ASR) (100 mg/kg ip in saline) 30 min before or 6 or 10 hr after CCl4 (1 ml/kg ip as a 20% v/v solution in olive oil) partially prevents the necrogenic effect of the hepatotoxin at 24 hr, but prevention of CCl4 fat accumulation was not observed. Protective action cannot be attributed to potential decreasing effects of ASR on CCl4 levels reaching the liver, on the covalent binding of CCl4-reactive metabolites to cellular components, or on CCl4-induced lipid peroxidation because ASR does not modify these parameters significantly. ASR administration increases GSH levels in livers of both control and CCl4-poisoned animals and decreases the calcium content of intoxicated animals at 24 hr of poisoning. ASR significantly lowers the body temperature of CCl4-treated animals at different times of the intoxication process. Present and previous results from our laboratory on the preventive effects of another very specific calcium chelator, calcion, and several anticalmodulins suggest that the beneficial effects of ASR might be associated with its calcium chelating ability. Other protective effects of ASR, such as lowering body temperature or increasing GSH content in liver, cannot be excluded.     

Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis

We previously reported that phenylmethylsulfonyl fluoride (PMSF) administration to rats (100 mg/kg, ip in olive oil) as late as 6 or 10 hr after CCl4 (1 ml/kg, ip as a 20% v/v solution in olive oil) can partially prevent the necrogenic response to the hepatotoxin at 24 hr. Here we confirm that observation by electron microscopy and provide further evidence that only in these circumstances were nuclear clumping of chromatin, slight dilatation of the endoplasmic reticulum, myelin figures and lipid droplets in the cytoplasm, large numbers of lysosomes and peroxisomes, glycogen, and slightly swollen mitochondria observable in the protected animals. A very minor part of the late protective effects of PMSF might be due to the effects of this drug on decreasing the intensity of covalent binding of CCl4-reactive metabolites or the intensity of CCl4-induced lipid peroxidation still occurring 6 or 10 hr after CCl4. PMSF administration did not prevent CCl4-induced decreases in cytochrome P450 content or glucose-6-phosphatase activity but partially prevented CCl4-induced calcium accumulation in liver. PMSF treatment increased glutathione and glycogen content in CCl4-poisoned animals, but did not markedly modify protein/phospholipid synthesis or degradation processes. Results suggest that the late protective effects of PMSF administration in CCl4-induced liver necrosis might be due to a favorable modulation of the calcium-calmodulin system similar to that previously described for other drugs.     

Studies on the mechanism of enhancement of carbon tetrachloride hepatotoxicity by Triton WR 1339.

Pretreatment of rats with Triton WR 1339 significantly enhanced the intensity of CC14-induced liver necrosis. Previous workers suggested that this effect might be due to enhancement by Triton WR 1339 of cellular degradative processes. This pretreatment, however, also enhanced the intensity of covalent binding of [14C]CC14 metabolites to microsomal protein at 3 or 6 h, but not 1 h after its administration. This effect is not due to changes of microsomal P-450 content or increased activity of mixed-function oxygenase-metabolizing drugs like pentobarbital. Pretreatment with Triton WR 1339 also partially increased CC14-induced peroxidation of microsomal lipids at 1, 3 or 6 h after administration of the hepatotoxin. Liver concentrations of CC14 in Triton WR 1339-treated rats were significantly higher at 3 or 6 h but not at 1, 10 or 24 after its i.p. administration. Triton WR 1339 treatment decreased the body temperature of the rats and further intensified the decrease produced by CC14. Results suggest that, in addition to possible effects of Triton WR 1339 administration on liver-cell degradative processes, there are other actions of this detergent on CC14 activation and lipid peroxidation which might play a role in the heightened response of the liver of CC14-induced injury.     

Carbon tetrachloride-induced early biochemical alterations but not necrosis in pigeon's liver

In contrast to what is well known to occur in rats, pigeons recelving CCl₄ (1 ml/kg i.p.) were not susceptible to necrogenic effects of the hepatotoxin at 24 h. There were, such as depression of glucose 6 phosphatase activity, decrease in the cytochrome P-450 content and in aminopyrine-N-demethylase activity in pigeon liver microsomes at 3 and 6 h after CCl₄ administration. Pigeon liver was able to activate CCl₄ to reactive metabolites that bind covalently to lipids, but no CCl₄-induced lipid peroxidation was proved by the diene hyperconjugation technique in pigeon liver microsomes at 1, 3 or 6 h after administration. Results suggest that covalent binding of CCl₄-reactive metabolities are more relevant to early biochemical alterations induced by CCl₄ than is lipid peroxidation. Absence of CCl₄-induced necrosis in pigeon liver could be attributabie to a smaller intensity of covalent binding interactions observed, when compared to susceptible specles, and to absence of lipid peroxidation.     

Pyrazole prevention of CC14-induced ultrastructural changes in rat liver.

Carbon tetrachloride (CC14) administration to rats leads to an early dilatation, vesiculation and disorganization of the liver endoplasmic reticulum (ER). This hepatotoxin also causes detachment of ribosomes from ER membranes, dilatation of the Golgi cisternae and occasionally dilatation of the perinuclear membrane. Prior treatment of the rats with pyrazole completely prevents CC14- induced ultrastructural alterations observed in liver at 3 h. This drug is known to decrease the intensity of the irreversible binding of CC14 reactive metabolites to cellular constituents without modifying the intensity of the CC14- induced lipid peroxidation, either in vitro or in vivo, as measured by the diene conjugation procedure or by decreases inthe arachidonic acid content of microsomal phospholipids. Results suggest that interaction of reactive metabolites rather than lipid peroxidation mediates deleterious effects of CCl4 on the liver ER.     

Studies on the mechanism of alloxan-diabetes potentiation of carbon tetrachloride-induced liver necrosis.

Carbon tetrachloride (CCl4)-induced liver necrosis in alloxan diabetic rats is markedly more intense than in controls as established by determination of isocitric dehydrogenase activity in plasma or by histological techniques. The covalent binding (CB) of CCl4 reactive metabolites to liver microsomal lipids is higher in alloxan diabetic rats than in controls. Cytochrome c reductase activity remains unchanged in alloxan diabetic rats. All the alterations described above observed in the diabetic animals are reverted by insulin administration. CCl4-induced lipid peroxidation of microsomal lipids, in contrast, is equally intense in controls than in alloxan diabetic animals and it is not modified by insulin treatment. Body temperature in alloxan diabetic animals treated with CCl4 is lower than in controls treated with the hepatotoxin. Results suggest that part of the enhanced necrogenic response of the liver observed in alloxan diabetic rats is due to increased CB to liver cell constituents but available evidence from the present and another work suggest that increased susceptibility of the liver from alloxan diabetic animals play a major role in the potentiation of CCl4 deleterious effects.     

Protection against carbon tetrachloride hepatotoxicity by pretreatment with indole-3-carbinol

The effects of administering indole-3-carbinol (I-3-C) on carbon tetrachloride (CCl4)-induced hepatotoxicity were examined. Mice received by gavage 0-150 mg I-3-C/kg body wt in methanol-extracted corn oil, followed 1 h later by 15 microliters CCl4/kg body wt in corn oil. Animals were sacrificed 24 h after receiving CCl4. Pretreatment with I-3-C reduced the degree of centrolobular necrosis, as observed histologically. Additionally, CCl4-mediated elevated serum enzymes were reduced by I-3-C. Although I-3-C induced elevated levels of cytochrome P-450 and associated mixed-function oxidase activity, the CCl4 depression of these parameters was not clearly reversed by I-3-C. However, CCl4 produced decreases in hepatic levels of glutathione (GSH), total reducing equivalents, and protein sulfhydryls, all of which were restored to control levels by I-3-C. Using mouse liver microsomes in an NADPH-fortified reaction mixture, I-3-C inhibited, in a concentration-dependent manner, CCl4-initiated lipid peroxidation, with 50% inhibition at 35-40 microM I-3-C. When mice were treated by gavage with 50 mg [14C]I-3-C/kg body wt, concentrations of radiolabel in the liver were greater than 100 microM after 1 hr. This was five times the level of radioactivity measured in blood and three times the concentration of I-3-C necessary for 50% inhibition of CCl4-mediated lipid peroxidation in vitro. The data are consistent with the hypothesis that I-3-C intervenes in CCl4-mediated hepatic necrosis by combining with reactive free radical metabolites of CCl4, thereby protecting critical cellular target sites.     

Effect of 3 amino 1,2,4 triazole administration on the early CCl4-induced ultrastructural alterations in rat liver.

CCl4 administration to rats caused at 3 and 6 h intense effects on the liver-cell endoplasmic reticulum such as dilatation, disorganization, detachment of ribosomes, development of extensive areas of smooth component (SER) and formation of myelin figures. 3 Amino 1,2,4 triazole administration (AT) at 3 and 6 h led to the formation of round small vesicles from the rough endoplasmic reticulum (RER), detachment of ribosomes, appearance of extensive areas of SER, appearance of elongated and distorted mitochondria with an increase in the number of peroxisomes. The administration of CCl4 to AT-pretreated animals led to a mutual cancellation of the effects on the RER, particularly remarkable at 3 h but still evident at 6 h; also, the formation of myelin figures was prevented. The other effects on cell ultrastructure exerted either by CCl4 or by AT were also observed with the combination of both chemicals. These observations reinforce the hypothesis about the need of either covalent binding of CCl4 metabolites to cellular constituents or lipid peroxidation, or both, in the origin of CCl4-induced alterations.     

Hepatoprotective effect of the natural fruit juice from Aronia melanocarpa on carbon tetrachloride-induced acute liver damage in rats.

The fruits of Aronia melanocarpa are rich in anthocyanins--plant pigments with anti-inflammatory and antioxidant activity. We studied the effect of the natural fruit juice from A. melanocarpa (NFJAM) on carbon tetrachloride (CCl4)-induced acute liver damage in rats. Histopathological changes such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins occurred in rats following acute exposure to CCl4 (0.2 ml kg(-1), 2 days). The administration of CCl4 increased plasma aspartate transaminase (AST) and alanine transaminase (ALT) activities, induced lipid peroxidation (as measured by malondialdehyde (MDA) content in rat liver and plasma) and caused a depletion of liver reduced glutathione (GSH). NFJAM (5, 10 and 20 ml kg(-1), 4 days) dose-dependently reduced the necrotic changes in rat liver and inhibited the increase of plasma AST and ALT activities, induced by CCl4 (0.2ml kg(-1), 3rd and 4th days). NFJAM also prevented the CCl4-induced elevation of MDA formation and depletion of GSH content in rat liver.     

Liver glutathione depletion induced by bromobenzene, iodobenzene, and diethylmaleate poisoning and its relation to lipid peroxidation and necrosis.

The mechanisms of bromobenzene and iodobenzene hepatotoxicity in vivo were studied in mice. Both the intoxications caused a progressive decrease in hepatic glutathione content. In both instances liver necrosis was evident only when the hepatic glutathione depletion reached a threshold value (3.5-2.5 nmol/mg protein). The same threshold value was evident for the occurrence of lipid peroxidation. Similar results were obtained in a group of mice sacrificed 15-20 hours after the administration of diethylmaleate, a drug which is mainly conjugated with hepatic glutathione without previous metabolism. The correlation between lipid peroxidation and liver necrosis was much more significant than that between covalent binding and liver necrosis. This fact supports the view that lipid peroxidation is the major candidate for the liver cell death produced by bromobenzene intoxication. Moreover, a dissociation of liver necrosis from covalent binding was observed in experiments in which Trolox C (a lower homolog of vitamin E) was administered after bromobenzene poisoning. The treatment with Trolox C, in fact, almost completely prevented both liver necrosis and lipid peroxidation, while not changing at all the extent of the covalent binding of bromobenzene metabolites to liver protein.     

Carbon tetrachloride-mediated lipid peroxidation induces early mitochondrial alterations in mouse liver

Although carbon tetrachloride (CCl(4))-induced acute and chronic hepatotoxicity have been extensively studied, little is known about the very early in vivo effects of this organic solvent on oxidative stress and mitochondrial function. In this study, mice were treated with CCl(4) (1.5?ml/kg ie 2.38?g/kg) and parameters related to liver damage, lipid peroxidation, stress/defense and mitochondria were studied 3?h later. Some CCl(4)-intoxicated mice were also pretreated with the cytochrome P450 2E1 inhibitor diethyldithiocarbamate or the antioxidants Trolox C and dehydroepiandrosterone. CCl(4) induced a moderate elevation of aminotransferases, swelling of centrilobular hepatocytes, lipid peroxidation, reduction of cytochrome P4502E1 mRNA levels and a massive increase in mRNA expression of heme oxygenase-1 and heat shock protein 70. Moreover, CCl(4) intoxication induced a severe decrease of mitochondrial respiratory chain complex IV activity, mitochondrial DNA depletion and damage as well as ultrastructural alterations. Whereas DDTC totally or partially prevented all these hepatic toxic events, both antioxidants protected only against liver lipid peroxidation and mitochondrial damage. Taken together, our results suggest that lipid peroxidation is primarily implicated in CCl(4)-induced early mitochondrial injury. However, lipid peroxidation-independent mechanisms seem to be involved in CCl(4)-induced early hepatocyte swelling and changes in expression of stress/defense-related genes. Antioxidant therapy may not be an efficient strategy to block early liver damage after CCl(4) intoxication.     

Effect of fermented Angelicae gigantis Radix on carbon tetrachloride-induced hepatotoxicity and oxidative stress in rats

This study is aimed to evaluate the protective effect of fermented Angelicae gigantis Radix (AGR) with Monascus purpureus strain on carbon tetrachloride (CCl(4))-induced hepatotoxicity and oxidative stress in rats. The activities of liver marker enzymes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and the levels of lipid peroxidation were increased when CCl(4) was treated but these parameters were significantly decreased by fermented AGR treatment. CCl(4) treatment exhibited decrease in serum concentrations of triglyceride, total cholesterol, HDL-cholesterol, and free fatty acids, and these were also decreased by fermented AGR administration. The level of serum leptin was significantly lower in fermented AGR administration than that in normal control group. CCl(4) treatment significantly increased the concentration of liver triglyceride. The current study observed significant elevations of the thiobarbituric acid-reactive substances (TBARS) levels in the liver homogenate, mitochondrial, and microsomal fractions of CCl(4) control group compared with normal control group. CCl(4) treatment resulted in a significant decrease in the levels of plasma and hepatic glutathione, but these reductions were significantly increased by fermented AGR administration. CCl(4) induced the marked hepatocytes necrosis and fatty accumulation around the central veins. Accordingly, fermented AGR may be an ideal candidate for the hepatoprotective effect in animal model.     

Further studies on the late preventive effects of the anticalmodulin trifluoperazine on carbon tetrachloride-induced liver necrosis

Trifluoperazine (TFP) (50 mg/kg ip) administration to rats 6 or 10 hr after CCl4 (1 ml/kg ip in olive oil) significantly prevented liver necrosis but not fatty liver caused by the hepatotoxin at 24 hr as evidenced by either histology or electron microscopy. TFP given 6 hr after CCl4 significantly decreased the CCl4-induced increases in liver calcium content. TFP raised four to five times the liver glycogen content in control rats but was unable to modify decreased glycogen content of CCl4 poisoned animals. TFP administration increased phospholipid and protein synthesis as evidenced by studies on 32P incorporation into microsomal phospholipid and by experiments on [14C]leucine incorporation in microsomal protein fractions from control rat livers. No significant changes were observed in microsomal phospholipid degradation as studied by decay of label from 32P-prelabeled microsomal lipids or in increased protein degradation as evidenced by decay of label from [14C-guanidino]arginine-prelabeled microsomal proteins found in livers of control rats after TFP treatment. Electron microscopy observations of liver from control animals treated with TFP evidenced accumulation of glycogen in areas close to smooth endoplasmic reticulum (SER); large Golgi areas with an abundant number of lysosomes, and minor dilatation effects on the rough endoplasmic reticulum (RER) and nuclear membrane. Results suggest that TFP preventive effects might be due to the anticalmodulin actions of this drug.     

Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats

ABSTRACT: BACKGROUND: Launaea procumbens (Asteraceae) is used as a folk medicine to treat hepatic disorders in Pakistan. The effect of a chloroform extract of Launaea procumbens (LPCE) was evaluated against carbon-tetrachloride (CCl4)-induced liver damage in rats. METHODS: To evaluate the hepatoprotective effects of LPCE, 36 male Sprague-Dawley rats were equally divided into six groups. Animals of group 1 (control) had free access to food and water. Group II received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for 4 weeks. Group III received 1 ml of silymarin via gavage (100 mg/kg b.w.) after 48 h of CCl4 treatment whereas groups IV and V were given 1 ml of LPCE (100 and 200 mg/kg b.w., respectively) after 48 h of CCl4 treatment. Group VI received 1 ml of LPCE (200 mg/kg b.w.) twice a week for 4 weeks. The activities of the antioxidant enzymes catalase, peroxidase (POD), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) were measured in liver homogenates. DNA damage, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology were studied in liver samples. Serum was analyzed for various biochemical parameters. Phytochemical composition in LPCE was determined through high-performance liquid chromatography (HPLC). RESULTS: LPCE inhibited lipid peroxidation, and reduced the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase in serum induced by CCl4. GSH contents were increased as were the activities of antioxidant enzymes (catalase, SOD, GST, GSR, GSH-Px) when altered due to CCl4 hepatotoxicity. Similarly, absolute liver weight, relative liver weight and the number of hepatic lesions were reduced with co-administration of LPCE. Phyochemical analyses of LPCE indicated that it contained catechin, kaempferol, rutin, hyperoside and myricetin. CONCLUSION: These results indicated that Launaea procumbens efficiently protected against the hepatotoxicity induced by CCl4 in rats, possibly through the antioxidant effects of flavonoids present in LPCE. KEYWORDS: Launaea procumbens, hepatic injuries, flavonoids, antioxidant enzymes, carbon tetrachloride.     

Mechanism of chloramphenicol prevention of carbon tetrachloride-induced liver damage

Chloramphenicol (CAP), when given prior to CCl₄, prevented the CCl₄-induced liver necrosis observed at either 24 or 72 hr after its administration. CAP administration did not modify either body temperature of the CCl₄-treated rats or the CCl₄ levels in the liver at different times after CCl₄ administration. Prior treatment of the rats with CAP decreased the extent of irreversible binding of ¹⁴CCl₄ to liver microsomal lipids, reduced CCl₄-induced lipid peroxidation, decreased CCl₄-induced polysome breakdown, and attenuated the dilation and vesiculation of the endoplasmic reticulum induced by CCl₄. The results are analyzed in relation to the hypothesis that drug-metabolizing enzymes and activation of CCl₄ are related to its hepatotoxic effects.     

Phytomedicinal activity of Terminalia arjuna against carbon tetrachloride induced cardiac oxidative stress.

Chronic and acute overproduction of reactive oxygen species (ROS) plays a positive role in the development of cardiovascular diseases under pathophysiological conditions. However, very little is known about carbon tetrachloride (CCl(4)) induced cardiac oxidative stress. The present study was conducted to find out CCl(4) induced oxidative insult in cardiac tissue and the cardioprotective effect of the 70% ethanol extractable active constituents of the bark of Terminalia arjuna (TA) against that stress in mice. Oral administration of CCl(4) at a dose of 1ml/kg body weight for 2 days significantly reduced the activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST), as well as depleted the level of reduced glutathione (GSH) in the cardiac tissue. In addition, extent of lipid peroxidation and the level of oxidized glutathione (GSSG) were increased under the same experimental conditions. Oral treatment of the active constituents of TA at a dose of 50mg/kg body weight for 7 days prior to CCl(4) administration significantly restored the activities of all antioxidant enzymes as well as increased the level of GSH and decreased the level of lipid peroxidation end products. In addition, FRAP assay showed that the active constituents of TA enhanced the cardiac intracellular antioxidant activity. Histological studies also supported the cardioprotective role of the active constituents. The active constituents-induced protective effect was compared with a known antioxidant, vitamin C. To the best of our knowledge, this is the first report describing the CCl(4) induced cardiac oxidative stress and cardioprotective action of the active phytoconstituents of Terminalia arjuna against that oxidative insult.     

Effect of pretreatment with artichoke extract on carbon tetrachloride-induced liver injury and oxidative stress.

Artichoke is a plant with antioxidant properties. In this study, we investigated the effect of artichoke extract pretreatment on carbon tetrachloride (CCl(4))-induced oxidative stress and hepatotoxicity. Rats were given artichoke leaf extract (1.5g/kg/day) by gavage for 2 weeks and after then CCl(4) (1ml/kg; i.p.) was applied. All rats were killed 24h after the CCl(4) injection. CCl(4) administration resulted in hepatic necrosis and significant increases in plasma transaminase activities as well as hepatic malondialdehyde (MDA) and diene conjugate (DC) levels in the liver of rats. Glutathione (GSH) and vitamin C levels decreased, but vitamin E levels increased in the liver of CCl(4)-treated rats. Hepatic superoxide dismutase (SOD) activities remained unchanged, but glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities decreased following CCl(4) treatment. In rats pretreated with artichoke extract, significant decreases in plasma transaminase activities and amelioration in histopathological changes in the liver were observed following CCl(4) treatment as compared to CCl(4)-treated rats. In addition, hepatic MDA and DC levels decreased, but GSH levels and GSH-Px activities increased without any change in other antioxidant parameters following CCl(4) treatment in artichoke-pretreated rats. The present findings indicate that in vivo architoke extract administration may be useful for the prevention of oxidative stress-induced hepatotoxicity.     

Protective effect of Launaea procumbens (L.) on lungs against CCl

ABSTRACT: BACKGROUND: Launaea procumbens (L.) is traditionally used in the treatment of various human ailments including pulmonary damages. The present study was arranged to evaluate the role of Launaea procumbens methanol extract (LME) against carbon tetrachloride (CCl4) induced oxidative pulmonary damages in rat. METHODS: 36 Sprague--Dawley male rats (170-180 g) were randomly divided into 06 groups. After a week of acclamization, group I was remained untreated while group II was given olive oil intraperitoneally (i.p.) and dimethyl sulfoxide (DMSO) orally, groups III, IV, V and VI were administered CCl4, 3 ml/kg body weight (30% in olive oil i.p.). Groups IV, V were treated with 100 mg/kg, 200 mg/kg of LME whereas group VI was administered with 50 mg/kg body weight of rutin (RT) after 48 h of CCl4 treatment for four weeks. Antioxidant profile in lungs were evaluated by estimating the activities of antioxidant enzymes; catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GSR), glutathione peroxidase (GSH-Px), quinone reductase (QR) and reduced glutathione (GSH). CCl4-induced lipid peroxidation was determined by measuring the level of thiobarbituric acid reactive substances (TBARS) with conjugation of deoxyribonucleic acid (DNA) damages, argyrophilic nucleolar organizer regions (AgNORs) counts and histopathology. RESULTS: Administration of CCl4 for 6 weeks significantly (p < 0.01) reduced the activities of antioxidant enzymes and GSH concentration while increased TBARS contents and DNA damages in lung samples. Co-treatment of LME and rutin restored the activities of antioxidant enzymes and GSH contents. Changes in TBARS concentration and DNA fragmentation were significantly (p < 0.01) decreased with the treatment of LME and rutin in lung. Changes induced with CCl4 in histopathology of lungs were significantly reduced with co-treatment of LME and rutin. CONCLUSION: Results of present study revealed that LME could protect the lung tissues against CCl4-induced oxidative stress possibly by improving the antioxidant defence system.