Free radical scavenging and hepatoprotective actions of Quercus aliena acorn extract against CCl4-induced liver

In the present study, we investigated the protective effect of Quercus aliena acorn extracts against CCl₄-induced hepatotoxicity in rats, and the mechanism underlying the protective effects. Aqueous extracts of Quercus aliena acorn had higher superoxide radical scavenging activity than other types of extracts. The Quercus aliena acorn extracts displayed dose-dependent superoxide radical scavenging activity (IC₅₀ = 4.92 μg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. Pretreatment with Quercus aliena acorn extracts reduced the increase in serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) levels. The hepatoprotective action was confirmed by histological observation. The aqueous extracts reversed CCl₄-induced liver injury and had an antioxidant action in assays of FeCl₂- ascorbic acid induced lipid peroxidation in rats. Expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by RT-PCR, was significantly decreased in the livers of Quercus aliena acorn-pretreated rats compared with the livers of the control group. These results suggest that the hepatoprotective effects of Quercus aliena acorn extract are related to its antioxidative activity and effect on the expression of CYP2E1.     

Antioxidant effects and hepatoprotective activity of 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene from Morus bombycis Koidzumi roots on CCl4-induced liver damage

We investigated hepatoprotective activity and antioxidant effect of the 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene that purified from Morus bombycis Koidzumi roots against CCl₄-induced liver damage in rats. The 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene displayed dose-dependent superoxide radical scavenging activity (IC₅₀ = 430.2 μg/ml), as assayed by the electron spin resonance (ESR) spin-trapping technique. The increase in aspartate aminotransferase (AST) activities in serum associated with carbon tetrachloride (CCl₄)-induced liver injury was inhibited by 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene and at a dose of 400 ～ 600 mg/kg samples had hepatoprotective activity comparable to the standard agent, silymarin. The biochemical assays were confirmed by histological observations showing that the 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene decreased cell ballooning in response to CCl₄ treatment. These results demonstrate that the 2,5-dihydroxy-4,3′-di(β-d-glucopyranosyloxy)-trans-stilbene is a potent antioxidant with a liver protective action against CCl₄-induced hepatotoxicity.     

Hepatoprotective effect of total flavonoids from Laggera alata against carbon tetrachloride-induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage

Summary The hepatoprotective activities of total flavonoids of Laggera alata (TFLA) were evaluated by carbon tetrachloride (CCl₄)-induced injury in primary cultured neonatal rat hepatocytes and in rats with hepatic damage. In vitro, TFLA at a concentration range of 1–100 g/ml improved cell viability and inhibited cellular leakage of two enzymes, hepatocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT), caused by CCl₄. In vivo, oral treatment with TFLA at doses of 50, 100, and 200 mg/kg significantly reduced the levels of AST, ALT, total protein, and albumin in serum and the hydroxyproline and sialic acid levels in liver. Histopathological examinations revealed that liver damage were improved when treated with TFLA. Meanwhile, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and superoxide radicals scavenging activities of TFLA were also determinated. To understand the exact components of TFLA responsible for the hepatoprotective effect, nine flavonoid compounds were isolated and identified from TFLA. In conclusion, the present investigation was the first to verify the hepatoprotective effect of L. alata in vitro and in vivo. The hepatoprotective action of TFLA is likely related to its potent antioxidative and anti-inflammatory activity. Neutralizing reactive oxygen species by nonenzymatic mechanisms and enhancing the activity of original natural hepatic-antioxidant enzymes may be the main mechanisms of TFLA against CCl₄-induced injury.     

Hepatoprotective Effect of Manganese Chloride Against CCl4-Induced Liver Injury in Rats

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl₄)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl₄-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl₄ increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus, the histopathalogical studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl₄-induced oxidative liver damage.     

Antioxidant and hepatoprotective activities of low molecular weight sulfated polysaccharide from Laminaria japonica

A low molecular weight sulfated polysaccharide (LMWF) was prepared from Laminaria japonica by mild acid hydrolysis. The antioxidant activity of LMWF in vitro was studied using three kinds of oxygen free radical systems. LMWF had effective scavenging abilities on superoxide radical, hydroxyl radical and hypochlorous acid directly in vitro. The hepatoprotective effect of LMWF was studied using two acute liver injury mice models induced by carbon tetrachloride (CCl₄) and D-galactosamine (D-GalN). Addition of LMWF significantly lowered the content of serum malonaldehyde and markedly increased the activities of superoxide dismutase and glutathione peroxidase, compared with the model groups in both kinds of liver injury mice. Moreover, administration of LMWF significantly inhibited the elevation of glutamate pyruvate transaminase induced by CCl₄ and D-GalN in mice. The results suggest that the antioxidant activity of LMWF plays an important role in its hepatoprotective effect in the liver injury mice induced by CCl₄ and D-GalN.     

Hepatoprotective effects of phosphatidylserine liposomes on carbon tetrachloride-induced hepatotoxicity in rats

It has been proposed carbon tetrachloride (CCl₄) intoxication due to the production of free radicals and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) overload results hepatotoxicity. Phosphatidylserine (PS) has shown antioxidant activity in numerous studies. Therefore, this study was aimed to investigate the effects of PS liposomes treatment against the CCl₄-induced hepatotoxicity in a rat model. Male Wistar rats were treated with PS (10 mg/kg, oral) or phosphatidylcholine liposomes (PC) (10 mg/kg, oral) for 3 days before CCl₄ (2 ml/kg; ip once on the third day) injection. The serum level of ALT, AST, and ALP were measured. Also, antioxidant assays were performed. Administration of PS with CCl₄ significantly inhibited alterations in the serum levels of AST, ALP (^**P < 0.01), and ALT (^***P < 0.001) compared with control group. Furthermore, measurement of malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) levels indicated that PS significantly reduced reactive oxygen species. The results of the present study showed the hepatoprotective effects of PS against CCl₄-induced hepatotoxicity in rats.     

Hepatoprotective,Immunomodulatory, and Anti-inflammatory Activities of Selenocystine in Experimental Liver Injury of Rats

The study was evaluated to investigate the efficacy of selenocystine (CysSeSeCys), a well-known organoselenium compound, on the prevention of carbon tetrachloride (CCl₄)-induced acute hepatic injury in Wistar rats. Forty healthy male Wistar rats were utilized in this study. Acute hepatotoxicity was induced by CCl₄ intoxication in rats. Serum biological analysis, oxidative stress, immune parameters, and gene expression of COX-2 and CYP2E1 were carried out. Pretreatment of CysSeSeCys prior to CCl₄ administration significantly prevented an increase in serum hepatic enzymatic activities. In addition, pretreatment of CysSeSeCys significantly prevented the formation of ROS, MDA, depletion of glutathione, and alteration of antioxidant enzyme activities in the liver of CCl₄-intoxicated rats. This study also revealed that pretreatment with CysSeSeCys normalized the levels of interleukin 6 and10, IgG, and CD4 cell count. Pretreatment of CysSeSeCys significantly reversed COX-2 inflammatory response and the upregulation of CYP2E1 expression as well. Histopathological changes induced by CCl₄ were also significantly attenuated by CysSeSeCys pretreatment. CysSeSeCys has a potent hepatoprotective effect on CCl₄-induced liver injury in rats through its antioxidative, immunomodulatory and anti-inflammatory activity.     

Podophyllum hexandrum aqueous extract as a potential free radical scavenger

Abstract

The present study was undertaken to evaluate the effect of the aqueous extract of Podophyllum hexandrum against free radical-mediated damage and also explore its anticancer activity. The extract exhibited significant activity in scavenging 1, 1-diphenyl-2-picryl-hydrazyl radicals, ^?OH radical-mediated DNA damage, and lipid peroxide production in rat liver microsomes. The extract was also tested for its reducing abilities. The activity of liver marker enzymes and antioxidant defense enzymes in rat liver homogenate was assessed in control and carbon tetrachloride (CCl₄)-treated animals. It was observed that CCl₄-induced changes viz., increases in the activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, a decrease in reduced glutathione as well as decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase. All these parameters showed reversal when pretreated with aqueous extract of P. hexandrum. Podophylotoxin and etoposide are the two known anticancer agents derived from P. hexandrum and interestingly the aqueous extract of P. hexandrum showed a typical DNA ladder formation in HL-60 cells confirming its role as an inducer of apoptosis. The results obtained suggest that the plant extract exhibits inhibition of and free radical production and lipid peroxidation, increase in antioxidant enzyme activities, revealing its antioxidant properties, and is also able to show potent anticancer activity as depicted by its ability to cause fragmentation of DNA.     

Propolis protects CYP 2E1 enzymatic activity and oxidative stress induced by carbon tetrachloride

Induction of CYP 2E1 by carbon tetrachloride (CCl₄) is one of the central pathways by which CCl₄ generates oxidative stress in hepatocytes. Experimental liver injury was induced in rats by CCl₄ to determine toxicological actions on CYP 2E1 by microsomal drug metabolizing enzymes. In this report, ethanolic extract of propolis at a dose of 200 mg/kg (po) was used after 24 h of toxicant administration to validate its protective potential. Intraperitoneal injection of CCl₄ (1.5 ml/kg) induced hepatotoxicity after 24 h of its administration that was associated with elevated malonyldialdehyde (index of lipid peroxidation), lactate dehydrogenase and γ-glutamyl transpeptidase release (index of a cytotoxic effect). Hepatic microsomal drug metabolizing enzymes of CYP 2E1 showed sharp depletion as assessed by estimating aniline hydroxylase and amidopyrine N-demethylase activity after CCl₄ exposure. Toxic effect of CCl₄ was evident on CYP 2E1 activity by increased hexobarbitone induced sleep time and bromosulphalein retention. Propolis extract showed significant improvement in the activity of both enzymes and suppressed toxicant induced increase in sleep time and bromosulphalein retention. Choleretic activity of liver did not show any sign of toxicity after propolis treatment at a dose of 200 mg/kg (id). Histopathological evaluation of the liver revealed that propolis reduced the incidence of liver lesions including hepatocyte swelling and lymphocytic infiltrations induced by CCl₄. Electron microscopic observations also showed improvement in ultrastructure of liver and substantiated recovery in biochemical parameters. Protective activity of propolis at 200 mg/kg dose was statistically compared with positive control silymarin (50 mg/kg, po), a known hepatoprotective drug seems to be better in preventing hepatic CYP 2E1 activity deviated by CCl₄. These results lead us to speculate that propolis may play hepatoprotective role via improved CYP 2E1 activity and reduced oxidative stress in living system.     

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl₄)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl₄ intoxication in rats. WFAC significantly reduced the CCl₄-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl₄-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl₄ were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl₄-induced hepatic injury.     

Protective effects of curcumin, α-lipoic acid,and <Emphasis Type="Italic">N</Emphasis>-acetylcysteine against carbon tetrachloride-induced liver fibrosis in rats

Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl₄)-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl₄ fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl₄-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.     

Free-radical scavenging by Ouratea parviflora in experimentally-induced liver injuries

Abstract

The antioxidant potential of crude extracts and fractions from leaves of Ouratea parviflora, a Brazilian medicinal plant used for the treatment of inflammatory diseases, was investigated in vitro through the scavenging of radicals 2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH), hydroxyl radical (HO^?), superoxide anion (O₂^??), and lipid peroxidation in rat liver homogenate. The crude extract (CEOP) and hydro-alcoholic fraction (OP4) showed strong inhibitory activity toward lipid peroxidation induced by tert-butyl peroxide (IC₅₀ = 2.3 ± 0.2 and 1.9 ± 0.1 μg/ml, respectively). The same products exhibited a strong concentration-dependent inhibition of deoxyribose oxidation (14.9 ± 0.2 and 0.2 ± 0.1 μg/ml, respectively), and also showed a considerable antioxidant activity against O₂^??(87.3 ± 0.1 and 73.1 ± 0.4 μg/ml, respectively) and DPPH radicals (55.4 ± 0.3 and 38.3 ± 0.4 μg/ml, respectively). The protective effects of CEOP and OP4 were also studied in mouse liver. CCl₄ significantly increased (by 90%) levels of lipid hydroperoxides, carbonyl protein content (64%), DNA damage index (133%), aspartate aminotransferase (261%), alanine aminotransferase (212%), catalase activity (23%), and also caused a decrease of 60% in GSH content. The results showed that CEOP and OP4 exerted cytoprotective effects against oxidative injury caused by CCl₄ in rat liver, probably related to the antioxidant activity showed by the in vitro free radical scavenging property.     

Hepatoprotective and antioxidant effects of Morus bombycis Koidzumi on CCl4-induced liver damage

The antioxidant activity and liver protective effect of Morus bombycis Koidzumi were investigated. Aqueous extracts of M. bombycis Koidzumi had higher superoxide radical scavenging activity than other types of extracts. The aqueous extract at a dose of 100 mg/kg showed significant hepatoprotective activity when compared with that of a standard agent. The biochemical results were confirmed by histological observations indicating that M. bombycis Koidzumi extract together with CCl(4) treatment decreased ballooning degeneration. The water extract recovered the CCl(4)-induced liver injury and showed antioxidant effects in assays of FeCl(2)-ascorbic acid-induced lipid peroxidation in rats. Based on these results, we suggest that the hepatoprotective effect of the M. bombycis Koidzumi extract is related to its antioxidative activity.     

<Emphasis Type="Italic">In vivo</Emphasis> and <Emphasis Type="Italic">in vitro</Emphasis> antioxidant effects of three Veronica species

The aim of the present study was to examine the antioxidant activity of three Veronica species (Plantaginaceae). The antioxidant potential of various extracts obtained from aerial flowering parts was evaluated by DPPH-free (1,1-diphenyl-2-picrylhydrazyl-free) radical scavenging activity and ferric-reducing antioxidant power assays. Considerable antioxidant activity was observed in the plant samples (FRAP values ranged from 0.97 to 4.85 mmol Fe²⁺/g, and DPPH IC₅₀ values from 12.58 to 66.34 μg/ml); however, these levels were lower than the activity of the control compound butylated hydroxytoluene (BHT) (FRAP: 10.58 mmol Fe²⁺/g; DPPH IC₅₀: 9.57 μg/ml). Also, the in vivo antioxidant effects were evaluated in several hepatic antioxidant systems in rats (activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase, glutathione content and level of thiobarbituric acid reactive substances) after treatment with different Veronica extracts, or in combination with carbon tetrachloride (CCl₄). Pretreatment with 100 mg/kg b.w. of Veronica extracts inhibited CCl₄-induced liver injury by decreasing TBA-RS level, increasing GSH content, and bringing the activities of CAT and Px to control levels. The present study suggests that the extracts analyzed could protect the liver cells from CCl₄-induced liver damage by their antioxidative effect on hepatocytes.     

Protective Effects of the Flavonoid-Rich Fraction from Rhizomes of Smilax glabra Roxb. on Carbon Tetrachloride-Induced Hepatotoxicity in Rats

Hepatoprotective agents could prevent tissue damage and reduce morbidity and mortality rates; such agents may include folkloric or alternative treatments. The present study evaluated the protective effects of the flavonoid-rich fraction from rhizomes of Smilax glabra Roxb. (SGF) on carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Sprague-Dawley male rats were orally treated with SGF daily and received CCl₄ intraperitoneally twice a week for 4 weeks. Our results showed that SGF at doses of 100, 300 and 500 mg/kg significantly reduced the elevated activities of serum aminotransferases (ALT and AST), alkaline phosphatase and lactate dehydrogenase and the level of hepatic thiobarbituric acid–reactive substances compared to the CCl₄-treated group. Moreover, SGF treatment was also found to significantly increase the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and glutathione compared with CCl₄-induced intoxicated liver. Histopathologic examination revealed that CCl₄-induced hepatic damage was markedly reversed by SGF. The results suggest that SGF has hepatoprotective and antioxidant properties in CCl₄-induced liver injury in rats.     

Hepatoprotective potential of new steroid against carbon tetrachloride-induced hepatic injury

The present study was designed to evaluate the hepatoprotective effects of newly isolated stigmast-4, 20 (21), 23-trien-3-one (STO) against carbon tetrachloride-induced hepatic injury in Wistar albino rats. Hepatotoxicity was induced by the administration of a single intraperitoneal dose of CCl₄ (0.5 mL/kg CCl₄ in olive oil) in experimental rats. Three different doses (2.5, 5.0, and 10 mg/kg, p.o) of STO was administered to the test groups during whole experimental protocol. Changes in the activity of serum ALT, AST, ALP, TB, and TP, anti-oxidant enzymes like SOD, CAT, GPx, GST, and LPO were studied in CCl₄-induced hepatocellular carcinogenesis. The altered levels of serum ALT, AST, ALP, TB, and TP restored toward normalization significantly by STO in a dose dependant manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. Meanwhile, it also produced a significant and dose-dependent reversal of CCl₄-diminished activity of anti-oxidant enzymes like SOD, CAT, GPx, GST, and the reduced CCl₄-elevated level of LPO. STO significantly prevented the increased levels of serum markers, also suppressed the free radical processes by scavenging hydroxyl radicals. It also modulates the levels of LPO and markedly increases the endogenous anti-oxidant enzymes level in CCl₄-induced hepatic injury.     

Exopolysaccharide-peptide complex from oyster mushroom (Pleurotus ostreatus) protects against hepatotoxicity in rats

Liver damage involves oxidative stress and a progression from chronic hepatitis to hepatocellular carcinoma (HCC). The increased incidence of liver disease in Egypt and other countries in the last decade, coupled with poor prognosis, justify the critical need to introduce alternative chemopreventive agents that may protect against liver damage. The aim of this study was to evaluate the efficacy of exopolysaccharide-peptide (PSP) complex extracted from Pleurotus ostreatus as a hepatoprotective agent against diethylnitrosamine (DEN)/carbon tetrachloride (CCL₄)-induced hepatocellular damage in rats. The levels of liver injury markers (ALT, AST and ALP) were substantially increased following DEN/CCl₄ treatment. DEN/CCl₄ - induced oxidative stress was confirmed by elevated levels of lipid peroxidation and decreased levels of superoxide dismutase, glutathione-S-transferase, and reduced glutathione. PSP reversed these alterations in the liver and serum, and provided protection evidenced by reversal of histopathological changes in the liver. The present study demonstrated that PSP extract from P. ostreatus exhibited hepatoprotective and antioxidant effects against DEN/CCl₄-induced hepatocellular damage in rats. Given the high prevalence of HCV-related liver damage in Egypt, our results suggest further clinical evaluation of P. ostreatus extracts and their potential hepatoprotective effects in patients with liver disease.     

Hepatoprotective effect of a protein-enriched fraction from the maggots (Musca domestica) against CCl4-induced hepatic damage in rats

The hepatoprotective potential of a protein-enriched fraction (PEF) isolated from the maggots of housefly (Musca domestica) was evaluated in rats against carbon tetrachloride (CCl₄)-induced acute hepatic damage. Activities of serum aspartate aminotransferase and alanine aminotransferase increased by 4- and 13-fold induced by CCl₄, were significantly inhibited by pretreatment with 50, 100 and 200 mg PEF/kg. The formation of malondialdehyde was also significantly decreased in PEF-treated group compared with CCl₄-treated group. The treatments with PEF also elevated total protein levels significantly. These results were further supplemented by histopathological examination of liver sections. Hyperplasia of kupffer cells was observed after treatment with PEF (100 and 200 mg/kg). We conclude that PEF is effective in this model of liver damage.     

Possible Protective Effect of Kolaviron on CCl4-Induced Erythrocyte Damage in Rats

The possible protective effect of kolaviron on rat erythrocytes followingsimultaneous administration of kolaviron (100 mg/kg of body weight/day) withcarbon tetrachloride CCl₄ (1.195 g/kg of body weight/day) by separateintraperitoneal injections was investigated.Kolaviron, a biflavonoid fraction of the defatted alcoholic extract ofGarcinia kola seed, inhibits the accumulation of lipid peroxidationproducts in erythrocytes. A significant reduction (p>0.05) by about34% of lipid peroxidation products was observed in erythrocytes of ratstreated simultaneously with CCl₄ and kolaviron when compared to CCl4-treatedrats. Similarly, the significant increase (p>0.05) in membranecholesterol observed in CCl₄-treated rats was significantly decreased(p>0.05) in rats treated simultaneously with CCl4 andkolaviron. Therefore, there was no significant difference (p>0.05) incholesterol–phospholipid ratio (C/P) of rats treated simultaneouslywith CCl₄ and kolaviron, and the controls. Thus, kolaviron normalizes theCCl₄-induced change in erythrocyte membrane composition.In addition, kolaviron antagonizes the effect of CCl₄ on the activity ofthe membrane bound enzyme, Ca²⁺-ATPase. These results suggest thatkolaviron protects erythrocyte membranes from free radical attack, on bothlipids and proteins.