Hepatoprotective Activity of Vitex trifolia against Carbon Tetrachloride-induced Hepatic Damage

Aqueous and ethanol extracts of leaf of Vitex trifolia was investigated for hepatoprotective activity against carbon tetrachloride induced liver damage. To assess the hepatoprotective activity of the extracts, various biochemical parameters viz., total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities were determined. Results of the serum biochemical estimations revealed significant reduction in total bilirubin and serum marker enzymes and increase in total protein in the animals treated with ethanol and aqueous extracts. However significant rise in these serum enzymes and decrease in total protein level was noticed in CCl4 treated group indicating the hepatic damage. The hepatoprotective activity is also supported by histological studies of liver tissue. Histology of the liver tissue treated with ethanol and aqueous extracts showed normal hepatic architecture with few fatty lobules. Hence the present study revealed that Vitex trifolia could afford significant protection against CCl₄ induced hepatocellular injury.     

Hepatoprotective activity of Amaranthus spinosus in experimental animals

The hepatoprotective and antioxidant activity of 50% ethanolic extract of whole plant of Amaranthus spinosus (ASE) was evaluated against carbon tetrachloride (CCl₄) induced hepatic damage in rats. The ASE at dose of 100, 200 and 400 mg/kg were administered orally once daily for fourteen days. The substantially elevated serum enzymatic levels of serum glutamate oxaloacetate transaminase (AST), serum glutamate pyruvate transaminase (ALT), serum alkaline phosphatase (SALP) and total bilirubin were restored towards normalization significantly by the ASE in a dose dependent manner. Higher dose exhibited significant hepatoprotective activity against carbon tetrachloride induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, in vivo antioxidant activities as malondialdehyde (MDA), hydroperoxides, reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were also screened which were also found significantly positive in a dose dependent manner. The results of this study strongly indicate that whole plants of A. spinosus have potent hepatoprotective activity against carbon tetrachloride induced hepatic damage in experimental animals. This study suggests that possible mechanism of this activity may be due to the presence of flavonoids and phenolics compound in the ASE which may be responsible to hepatoprotective activity.     

Protective Effect of Ethanol Extract of Gymnosporia montana (Roth) Bemth. in Paracetamol-induced Hepatotoxicity in Rats

The aim of the present study was to explore the hepatoprotective activity of the ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family: Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of paracetamol and studied by comparing parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and histopathological examination of liver. Pre and post-treatment with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100 mg/kg was studied by comparing the above mentioned parameters with silymarin (100 mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth) Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg produced effects comparable to those of silymarin. The present study indicates that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant hepatoprotective activity.     

Effect of l-ornithine l-aspartate against thioacetamide-induced hepatic damage in rats

Objective:

To investigate the hepatoprotective activity of L-ornithine-L-aspartate against thioacetamide (TAA)-induced hepataopathy in rats.

Materials and Methods:

The hepatoprotective activity of L-ornithine-L-aspartate (OA) at a dose of 2 g/kg, p.o. for 10 days was evaluated against TAA (250 mg/kg, i.p. for 2 days) induced hepatopathy in rats. Biochemical parameters such as serum aspartate transaminase, alanine transaminase, alkaline phosphatase, bilirubin and glutathione, thiobarbituric acid reactive substances, and protein in liver tissues were estimated to assess the liver function.

Results:

TAA-induced pathogenic changes in the levels of the above indices were significantly (P < 0.01) reversed by the OA treatment. OA treatment also exhibited significant restoration of the hepatic architecture and lobular structure in histological evaluation of the rat liver sections.

Conclusion:

Ornithine aspartate exhibited significant hepatoprotective activity against TAA-induced hepatic damage in rats.     

Development and Evaluation of Hepatoprotective Polyherbal Formulation Containing Some Indigenous Medicinal Plants

The present study explores the hepatoprotective activity of various extracts of Ferula asafoetida, Momordica charantia Linn and Nardostachys jatamansi against experimental hepatotoxicity. Polyherbal suspensions were formulated using extracts showing significant activity and evaluated for both physicochemical and hepatoprotective activity in comparison with LIV-52 as standard. Petroleum ether (60-80°), chloroform, benzene, ethanol and aqueous extracts of Ferula asafetida, Momordica charantia Linn and Nardostachys jatamansi were evaluated for hepatoprotective activity against carbon tetrachloride-induced liver toxicity in Wistar rats. Polyherbal suspensions were prepared by the trituration method using a suspending agent and other excipients. Formulation F3 has shown significant hepatoprotective effect by reducing the elevated serum enzyme levels such as glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase. These biochemical observations were supplemented by histopathological examination of liver sections. Various parameters evaluated for all formulations were within the official specifications. Experimental data suggested that treatment with formulation F3 enhances the recovery from carbon tetra chloride-induced hepatotoxicity. From these results it may be concluded that the F3 formulation (containing chloroform, petroleum ether and aqueous extracts of Ferula asafetida, petroleum ether and ethanol extracts of Momordica charantia Linn. and petroleum ether and ethanol extracts of Nardostachys jatamansi) demonstrated significant hepatoprotective activity, that might be due to combined effect of all these extracts.     

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.     

Antihepatotoxic activity of ferolactone, a new furanocoumarin from Feronia limonia

The Fruit of Feronia limonia Swingle (Rutaceae) afforded a new furanocoumarin, characterized as Monoterpenoid-5-methoxy furanocoumarin lactone, named as ferolactone. Ferolactone exhibited a significant antihepatotoxic activity by reducing the elevated levels of serum enzymes such as serum glutamate oxaloacetate transaminase (SGOT) by 43.44%, serum glutamate pyruvate oxaloacetate transaminase (SGPT) by 39.63%, and alkaline phosphatase (ALP) by 41.16%; while the total protein (TP) levels were increased by 36.15%. When compared with standard drug, silymarin decreased SGOT by 45.80%, SGPT by 43.67%, ALP by 37.96%, and increased TP levels by 55.16%, against CCl₄-induced toxicity in albino wistar rats. These biochemical observations were also supplemented by histopathological examinations of the liver sections, which showed significant recovery of hepatocytes of the liver in ferolactone-treated animals.     

Antihepatotoxic activity of a sterol glucoside from aerial parts of Clerodendrum phlomidis

We isolated a sterol glucoside from ethanol extract of aerial parts of Clerodendrum phlomidis. Chemical structure was identified as 24-ethyl-cholesta-5(6), 22(23), 25(26)-triene-3-O-β-d-glucopyranoside was a rare glucoside of 22-dehydroclerosterol. It was isolated for the first time from this plant. Compound (1) has shown significant antihepatotoxic activity by decreasing the elevated levels of serum enzymes such as serum glutamate oxaloacetate transaminase (SGOT) by 57.71%, serum glutamate pyruvate oxaloacetate transaminase (SGPT) by 52.25%, and alkaline phosphatase (ALP) by 93.14%; while the total protein (TP) levels were increased by 100.47%, When compared with standard drug silymarin that have decreased SGOT by 77.03%, SGPT by 69.67%, ALP by 93.14%, and increased TP levels by 100.47%, against CCl₄-induced toxicity in albino wistar rats. The biochemical parameters also showed the significant antihepatotoxic activity.     

Investigations of Free Anthraquinones from Rhubarb Against α‐Naphthylisothiocyanate‐induced Cholestatic Liver Injury in Rats

Abstract: The protective effects of anthraquinones from Rhubarb, a Chinese herbal medicine, consisting of the root and rhizome of Rheum palmatum L., R. tanguticum Maxim. Ex Balf., or R. officinale Baill. (family Polygonaceae) were investigated and compared in rats with liver injury induced by α‐naphthylisothiocyanate. α‐Naphthylisothiocyanate was given intragastrically in rats, liver injury with cholestasis developed within 36 hrs, as indicated by characteristic serum levels of glutamate‐pyruvate transaminase, glutamic oxaloacetic transaminase, total bilirubin, direct bilirubin, alkaline phosphatase, γ‐glutamyltransferase and total bile acid. The intragastrical administration of rhein, aloe‐emodin and physione to α‐naphthylisothiocyanate‐treated rats reduced significantly the serum level of both glutamate‐pyruvate transaminase, glutamic oxaloacetic transaminase and the serum total bilirubin, direct bilirubin, alkaline phosphatase, γ‐glutamyltransferase and total bile acid. For all hepatic biochemical markers and cholestasis index, rhein was most efficient. By comparison, the administration of emodin and chrysophanol did not reduce the serum levels of hepatic enzymes glutamate‐pyruvate transaminase and glutamic oxaloacetic transaminase but decreased the levels of serum total bilirubin, direct bilirubin, alkaline phosphatase, γ‐glutamyltransferase, and total bile acid, showing their partial protective effects on cholestatic liver injury. The liver in α‐naphthylisothiocyanate‐treated rats showed cholangiolitic hepatitis characterized by intrahepatic cholestasis, necrosis of hepatocytes and biliary epithelial cells and bile obstruction. The concurrent intragastrical administration of rhein reduced the severity of all morphological alteration, especially the neutrophil infiltration and sinusoid congestion. Rhein, aloe‐emodin, and physione all exhibited protective effects on hepatocytes and cholangiocytes against α‐naphthylisothiocyanate‐induced damage, whereas emodin and chrystophanol provided partial protection.     

Effect of ethanol on carbon tetrachloride levels and hepatotoxicity after acute carbon tetrachloride poisoning

To study the effect of an acute dose of ethanol on carbon tetrachloride (CCl₄) concentration and hepatotoxicity, female rats received ethanol (2.5 ml/kg body wt.) either intragastrically or intraperitoneally following intragastric administration of CCl₄ (1.5 ml/kg body wt.). Three hours after acute CCl₄ intoxication there was a striking increase in CCl₄ concentration in animals treated simultaneously with ethanol intragastrically compared to those receiving ethanol intraperitoneally. This increase was significant (P<0.05) and amounted to 211% for blood, 236% for liver and 405% for fat tissue, whereas animals treated with CCl₄ alone showed CCl₄ concentrations in the range between the two other experimental groups. Serum activities of glutamate oxalacetate transaminase, glutamate pyruvate transaminase and glutamate dehydrogenase were found to be considerably higher in animals treated with the combination of CCl₄ and ethanol when compared to those receiving CCl₄ alone, showing that ethanol given intraperitoneally or intragastrically enhances CCl₄ hepatotoxicity. Since the intraperitoneal administration of ethanol led to a reduction rather than an increase in CCl₄ concentration in the early phase of intoxication, additional mechanisms independent of actual levels of CCl₄, such as direct effects of ethanol on the CCl₄ metabolizing enzyme of the membrane of the endoplasmic reticulum, have to be implicated in the pathogenesis of the potentiation of CCl₄ hepatotoxicity by ethanol.     

Carotenoid lutein protects rats from paracetamol‐, carbon tetrachloride‐ and ethanol‐induced hepatic damage

Objectives Carotenoids are a class of natural fat‐soluble pigments that are found in many fruits and vegetables. Consumption of a diet rich in carotenoids has been epidemiologically correlated with a lower risk for several diseases. In the present study the carotenoid lutein (3,3′‐dihydroxy‐β,ε‐carotene) was evaluated for its hepatoprotective activity in rats. Methods Paracetamol, 20% ethanol and carbon tetrachloride were used to induce liver toxicity. Key findings Levels of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase and alkaline phosphatases, which were increased in the serum, were found to be significantly reduced by the treatment of lutein in a dose‐dependent manner, indicating that lutein may reduce the hepatotoxicity induced by these agents_. Serum bilirubin was also significantly lower in lutein‐treated groups compared with control. Increased lipid peroxidation, conjugated diene and hydroperoxides in the liver tissue produced by the administration of paracetamol were found to be reduced in the lutein‐treated groups. Levels of antioxidant enzymes, like superoxide dismutase, catalase, glutathione peroxidase and glutathione, were found to be increased in lutein‐treated groups compared with control group during alcohol‐ and CCl₄‐induced liver toxicity. Hydroxyproline, which is an indicator of fibrosis in liver tissue, was high in the ethanol‐treated control group. Hydroxyproline levels were decreased by simultaneous lutein administration. Conclusions Histopathological evidence confirmed the protection offered by lutein from the tissue damage caused by hepatotoxins. The hepatoprotective action may be due to lutein's ability to scavenge reactive oxygen radicals.     

Protective role of curcumin in myocardial oxidative damage induced by isoproterenol in rats

This study was designed to investigate the effect of oral curcumin pretreatment (200 mg/kg) on isoproterenol-induced myocardial injury in rats. Isoproterenol (85 mg/kg, s.c., in two divided doses at 24 h intervals) administration induced a statistically significant increase (P < 0.01) in serum lactate dehydrogenase, creatine kinase, aspartate transaminase, and alanine transaminase activities and significant increase (P < 0.01) in myocardial lipid peroxides levels as compared to vehicle control rats. Furthermore, significant depletion (P < 0.01) of myocardial endogenous antioxidants viz. superoxide dismutase, catalase, and tissue glutathione levels were also found in the pathogenic control group, that is, isoproterenol only treated animals. Curcumin (200 mg/kg) pretreatment for 20 days in isoproterenol treated rats significantly lowered (P < 0.01) the serum lactate dehydrogenase, creatine kinase, aspartate transaminase, alanine transaminase, and myocardial lipid peroxides levels and increased the levels of myocardial endogenous antioxidants (superoxide dismutase, catalase, and tissue glutathione) as compared to pathogenic control rats. Furthermore, histological examination of rat's heart section confirmed myocardial injury with isoproterenol administration and near normal pattern with curcumin pretreatment. The results of our study provide clear evidence that the curcumin pretreatment enhances the antioxidant defense against isoproterenol-induced oxidative myocardial injury in rats and exhibit cardioprotective property.     

Hypoglycemic effects of Citrullus colocynthis roots

The aim of this study was to examine the effect of root of C. colocynthis on the biochemical parameters of normal and alloxan-induced diabetic rats. Diabetes mellitus was induced by intraperitoneal (120 mg/kg b.w.) injection of alloxan monohydrate for three days and the animals showing blood glucose level in the range of 175-300 mg/dL were selected for study. The blood glucose concentrations of the animals were measured at the beginning of the study and the measurements were repeated on 3rd, 5th and 7th day after the start of the experiment. On day 7, blood was collected by cardiac puncture under mild ether anesthesia. Aqueous extract of roots of Citrullus colocynthis showed significant reduction in blood sugar level (58.70%) when compared with chloroform (34.72%) and ethanol extracts (36.60%) (p < 0.01). The aqueous extracts showed improvement in parameters like body weight, serum creatinine, serum urea and serum protein as well as lipid profile and also restored the serum level of bilirubin total, conjugated bilirubin, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP).     

Evaluation of the hepatroprotective and nephroprotective activities of Scrophularia hypericifolia growing in Saudi Arabia

The hepatroprotective and nephroprotective effects of the ethanol extract of the aerial parts of Scrophularia hypericifolia growing in Saudi Arabia were evaluated at 250 and 500 mg kg⁻¹ doses using Wistar albino rats as experimental animal model. Toxic doses of paracetamol were used to induce liver and kidney toxicities, while the standard drug silymarin was used as reference. The biochemical parameters such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT) and total bilirubin were estimated as reflections of the liver condition. Kidney condition was investigated through measurement of serum urea, serum creatinine, sodium and potassium levels. Liver and kidney samples of rats treated with 500 mg kg⁻¹ of the extract were subjected to the histopathological study. The ethanol extract of the aerial parts of S. hypericifolia showed dose dependent moderate level of protection against paracetamol induced hepatrotoxicity and nephrotoxicity as indicated from the obtained results. The reduction of the sodium and potassium levels by the higher dose of the extract exceeded that obtained by silymarin.     

Hepatoprotective activity of Stereospermum suaveolens against CCl4-induced liver damage in albino rats

The present study aims to evaluate the hepatoprotective activity of Stereospermum suaveolens DC (Bignoniaceae). Hepatoprotective activity is studied by carbon tetrachloride (CCl₄)-induced liver damage in albino rats. The degree of protection in this activity has been measured by using biochemical parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, LDL-cholesterol and SOD, CAT, GSH, total thiols, NO, and lipid peroxidation in liver tissue homogenate. The results suggest that the methanol stem bark extract of Stereospermum suaveolens at the doses 125, 250, and 500?mg/kg and reference standard Liv-52 treated group produced significant (p <0.001) hepatoprotection against CCl₄-induced liver damage by decreasing the activities of serum enzymes, bilirubin and lipid peroxidation. The extract significantly (p <0.001) increased levels of SOD, CAT, GSH and total thiols, as compared to control group. Histopathological studies further substantiate the protective effect of the extract. It was concluded that methanol stem bark extract of Stereospermum suaveolens showed effective hepatoprotective activity.     

Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.     

Anti-diabetic and anti-oxidative effect of composite extract of leaves of some Indian plants on alloxan induced diabetic wistar rats

Use of plant based remedies for the prevention and treatment of diabetic complications over conventional therapies have received much emphasis in recent years. Present study was performed to evaluate the protective effect of composite extract (CE) of leaves of Aegle marmelos, Ocimum sanctum, Murraya koenigii and Azadirachta indica on biochemical alterations in alloxan (ALX) induced diabetic wistar rats. Diabetes was induced in rats by a single administration of ALX (150 mg/kg intraperitoneal (i.p) and CE at three different doses (25, 50 and 100 mg/kg/bw/day) were administrated orally in three group of diabetic rats for 35 days. Another group of same number of diabetic rats were administrated by insulin (6 unit/kg/bw/day) by subcutaneous injection for 35 days and used as standard. Results showed that oral administration of CE significantly protected the biochemical impairments in diabetic rats as evidenced by restoration of glutathione depletion, ascorbic acid level, plasma antioxidant values and inhibition of lipid peroxidation. The outcome of the study suggests that CE of A. marmelos, O. sanctum, M. koenigii and A. indica leaves mimics insulin and passes capacity to ameliorate the hyperglycemia induced cellular complications thus may control the development and progression of diabetes.     

Protective Effect of Enicostemma littorale. against CCl4-Induced Hepatic Damage in Rats

Abstract

The alcohol extract of the whole plant of Enicostemma littorale. Blume was evaluated for its antihepatotoxic activity against CCl₄-induced hepatic damage in rats. The activity was evaluated by using biochemical parameters, such as serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, total bilirubin, and γ.-glutamate transpeptidase. The histopathological changes of liver sample were compared with respective controls. The extract showed a remarkable hepatoprotective effect.     

Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats

Objectives:

The present study evaluates the hepatoprotective activity of N-acetyl cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity.

Materials and Methods:

Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC 50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were killed, liver was separated, weighed and the levels of antioxidants and liver enzymes were estimated. In addition, histopathological investigation was also performed.

Results:

Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT) transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute and relative liver weights were significantly (P < 0.05) elevated, whereas serum levels of albumin, total protein and body weight were decreased in the CBZ-treated animals. CBZ also produced vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. NAC significantly reduced the levels of serum transaminase, ALP, bilirubin and liver weight and increased the levels of total protein, albumin and body weight.

Conclusion:

It was observed that NAC increased the glutathione (GSH) content, reduced lipid peroxidation and reversed the CBZ-induced histopathological abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite-induced oxidative stress.KEY WORDS: Carbamazepine, hepatotoxicity, N-acetyl cysteine, oxidative stress     

The effect of total parenteral nutrition on the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat

The effects of total parenteral nutrition (TPN) upon the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in rats has been studied. At doses of 50 or 100 μg/kg, TPN-fed, TCDD-treated rats demonstrated a weight gain similar to that of TPN-fed controls, but died at Days 13–17 following treatment. Gross examination of moribund animals revealed icterus, thymic atrophy, increased adipose tissue depots, and enlarged livers. The liver weights ranged from two to three times those from TPN-fed control animals. Histologically the livers were severely necrotic. Most cells which were not necrotic were markedly swollen and disorganized. Extensive vacuolization of hepatocytes and cystic areas containing cell debris were also prominent features. Whereas glycogen stores were depleted, the total content of water, lipid, protein, RNA, and DNA in the livers was increased. Alterations in cytochrome P-450-associated monooxygenase activities were also observed. Statistically significant increases in serum iron, bilirubin, alkaline phosphatase, serum glutamic-oxaloacetic transaminase and cholesterol were found in the TPN-fed, TCDD-treated animals. Serum protein, glucose, and triglycerides were significantly decreased except in a few severely moribund animals in which hyperglycemia was observed. The results in the TPN-fed, TCDD-treated rats were compared with TCDD-treated rats fed a chow diet ad libitum. At the same dose of TCDD, the liver damage in the TPN-fed, TCDD-treated rats was histologically more severe.