Hepatoprotection of D-galactosamine-induced toxicity in mice by purified fractions from Garcinia kola seeds

The hepatoprotective effect of a biflavonoid complex, kolaviron, and its fractions from Garcinia kola seeds, together with the possible mechanisms involved was investigated in mice intoxicated with a single dose of D-galactosamine (GalNH(2)). Likewise, the ability of vitamin E to attenuate the toxicity was examined. Kolaviron, was separated by thin-layer chromatographic technique into three fractions; Fraction I, Fraction II and Fraction III with RF values of 0.48, 0.71 and 0.76, respectively. Pretreatment with kolaviron, fraction I and fraction II at a dose of 100 mg/kg for seven consecutive days before challenge with a single dose of GalNH(2) (800 mg/ kg) significantly (P<0.05) decreased serum alanine (ALT) and aspartate (AST) aminotransferases by 67%, 70%, 71% and 39%, 35%, 46%, respectively over GalNH(2)-only intoxicated mice. Vitamin E elicited respectively 65% and 39% reduction in the GalNH(2)-induced increase in the activities of these enzymes. In addition, pretreatment with kolaviron and fraction II significantly (P<0.05) decreased the activity of microsomal gamma-glutamyl transferase (gamma-GT) by 42% and 46%, respectively. Administration of kolaviron to GalNH(2)-intoxicated mice also restored glucose-6-phosphatase to level that was comparable to the control (P<0.05). These extracts except fraction III prevented the accumulation of serum and microsomal lipid peroxidation products, and also prevented the depletion of reduced glutathione (GSH) levels in the liver of GalNH(2)-intoxicated mice. Kolaviron, fraction I and fraction II at a dose of 100 mg/kg caused an induction of glutathione-S-transferase (GSH transferase) and uridyl glucuronosyl transferase (UDPGT) activities by 31%, 34%, 35% and 29%, 65%, 56%, respectively. GalNH(2)-induced toxicity was essentially prevented as indicated by a liver histopathologic study of liver slices from mice pretreated with kolaviron, fraction I and fraction II. This study shows that treatment with kolaviron, fraction I and fraction II (purified fractions from Garcinia kola) appeared to enhance the recovery from GalNH(2)-induced hepatotoxicity, and that the fractions I and II may therefore be responsible for the observed antihepatotoxic effect of kolaviron. This protection may be due to the ability of these extracts to induce the expression of phase II drug metabolizing enzymes.     

Possible anti-atherogenic effect of kolaviron (a Garcinia kola seed extract) in hypercholesterolaemic rats

1. The hypolipidaemic effect of kolaviron, a mixture of Garcinia biflavonoid 1 (GB1), Garcinia biflavonoid 2 (GB2) and kolaflavanone, used in the treatment of various ailments in southern Nigeria, was investigated in rats. The ability of Questran (Bristol-Myers Squibb, Hounslow, UK), a hypolipidaemic therapeutic drug, to attenuate hypercholesterolaemia in rats was also examined. 2. In order to assess the hypolipidaemic effect of this extract in experimental animals, thiobarbituric acid-reactive substances (TBARS), cholesterol, phospholipid, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglyceride levels were determined in the plasma and liver. 3. Cholesterol administered orally to rats at a dose of 30 mg/0.3 mL five times a week for 8 consecutive weeks resulted in a significant increase (P<0.001) in the relative weight of the heart of hypercholesterolaemic animals compared with control. However, cotreatment with kolaviron and Questran ameliorated the cholesterol-induced enlargement of the heart. Kolaviron (100 and 200 mg/kg) elicited 88.5 and 87.4% reductions, respectively, in plasma cholesterol levels of pretreated animals compared with the cholesterol-fed group. In addition, kolaviron produced a significant decrease (P<0.05) in post-mitochondrial fraction (PMF) cholesterol levels in treated animals compared with untreated hypercholesterolaemic animals. Similarly, Questran significantly decreased (P<0.05) the cholesterol-induced increase in plasma cholesterol levels compared with untreated hypercholesterolaemic animals. In addition, (100 and 200 mg/kg) significantly (P<0.05) decreased plasma LDL-C levels by over 70% in treated animals compared with untreated hypercholesterolaemic animals. Similarly, kolaviron significantly decreased (P<0.05) PMF LDL-C levels by over 60% in treated animals compared with untreated hypercholesterolaemic animals. 4. The significantly (P<0.05) higher values of plasma and PMF triglycerides obtained in cholesterol-fed animals compared with control animals were unaltered following cotreatment with kolaviron and Questran. In the present study, there was a significant decrease (P<0.05) in plasma formation of malondialdehyde in kolaviron- and Questran-treated animals compared with untreated hypercholesterolaemic animals. 5. The results of the present study demonstrate that kolaviron exerts a hypocholesterolaemic effect and reduces the relative weight of the heart in cholesterol-fed animals. This reduction and the favourable lipid profile indicate a possible anti-atherogenic property of the extract.     

Kolaviron,a Natural Antioxidant and Anti‐Inflammatory Phytochemical Prevents Dextran Sulphate Sodium‐Induced Colitis in Rats

The beneficial effects of kolaviron, a natural biflavonoid from the seeds of Garcinia kola, have been attributed mainly to its antioxidant and anti‐inflammatory effects. This study investigated these effects on dextran sulphate sodium (DSS)‐induced ulcerative colitis in rats. Sulfasalazine served as standard reference in this study. Kolaviron and sulfasalazine were separately co‐administered orally at 200 mg/kg and 500 mg/kg, respectively, to dextran sulphate sodium‐exposed rats for 5 days. The result indicated that kolaviron or sulfasalazine significantly prevented DSS‐induced body weight loss as well as the incidence of diarrhoea and bleeding in DSS‐exposed rats. Kolaviron suppressed the DSS‐mediated increase in colonic nitric oxide concentration and myeloperoxidase activity and significantly prevented the increase in inflammatory mediators, interleukin‐1β and tumour necrosis factor alpha, in the colon of DSS‐treated rats. The significant depletion in colonic antioxidant status in rats exposed to DSS alone was evident by marked reduction in colonic catalase and glutathione S‐transferase activities as well as glutathione content, leading to elevated hydrogen peroxide and lipid peroxidation levels. Histopathologically, DSS alone resulted in severe epithelial erosion, total absence of goblet cells, destruction of the crypts, necrotic and distorted glands, accompanied by marked cellular mononuclear cells infiltration. However, administration of kolaviron and sulfasalazine ameliorated DSS‐induced colitis by increasing the antioxidant status decreased hydrogen peroxide and lipid peroxidation levels and attenuated the adverse effect of DSS on colon architecture. In conclusion, the anti‐colitis effect of kolaviron is related to its intrinsic anti‐inflammatory and anti‐oxidative properties.     

Mechanisms for the hepatoprotective action of kolaviron: studies on hepatic enzymes, microsomal lipids and lipid peroxidation in carbontetrachloride-treated rats.

The present work examines the protective mechanisms of a biflavonoid fraction of an extract from Garcinia kola seeds, kolaviron, in rats treated with carbontetrachloride (CCl(4)). CCl(4)administered at a dose of 1.2 g kg(-1), three times a week for 2 weeks, significantly depressed the activities of microsomal aniline hydroxylase, aminopyrine N -demethylase, ethoxyresorufin O -demethylase and p -nitroanisole O -demethylase. Kolaviron (200 mg kg(-1)), administered for 14 days consecutively, inhibited (P<0.001) the CCl(4)mediated decrease in the activities of these enzymes by 60, 65, 55, and 63%, respectively. Kolaviron reduced the CCl(4)increase in the cholesterol/phospholipid ratio. Similarly, kolaviron attenuated the toxic onslaught imposed by CCl(4)on 5'nucleotidase, glucose 6-phosphatase (microsomal marker enzymes) and malondialdehyde formation by 41, 54 and 77%, respectively. Kolaviron elicited 168% and 234% increases in the activity of UDP-glucuronosyl transferase and glutathione S -transferase. Simultaneous administration of kolaviron with CCl(4)modulated the effect of CCl(4)on the activities of these enzymes. On the basis of the above data, it can be postulated that kolaviron exerts its protective action against carcinogen-induced liver damage, first, by acting as an in vivo natural antioxidant and, second, by enhancement of drug-detoxifying enzymes.     

Kolaviron modulates cellular redox status and impairment of membrane protein activities induced by potassium bromate (KBrO(3)) in rats.

In this study, we examined the modulatory effects of kolaviron, a biflavonoid from Garcinia kola seeds on the antioxidant defense mechanisms, cellular redox status and oxidative stress in the kidney and liver of rats pretreated with potassium bromate (KBrO(3)) intragastrically as a single dose of 300 mg kg(-1)weight for 4 weeks. Treatment of rats with KBrO(3)resulted in an insignificant difference (P> 0.05) in body weight compared to controls. However, a significant increase in kidney/body weight ratio (P< 0.001) was observed in rats treated with KBrO(3)while liver/body weight ratio was not affected. KBrO(3)depressed the activities of superoxide dismutase, glutathione peroxidase and catalase (P< 0.001) in the kidney but not in the liver. Kolaviron (200 mg kg(-1)body weight) administered three times a week for 4 weeks inhibited the decrease mediated by KBrO(3)of these enzymes in the kidney by 29, 88 and 45%, respectively. Similarly, kolaviron reduced the KBrO(3)-induced decrease in the activities of gamma -glutamyltransferase and microsomal Ca(2+)ATPase by 73 and 63% in the kidney. In addition, the extract elicited a 27 and 25% decrease in the KBrO(3)-induced increase in malondialdehyde and lipid hydroperoxide formation in the kidney. Kolaviron also attenuated the KBrO(3)-decreased activities of glucose 6-phosphatase, 5 prime prime or minute nucleotidase and alkaline phosphatase (membrane enzymes) by 72, 57 and 25% respectively. The results of the present investigation indicate the antioxidative effect of kolaviron, a natural antioxidant, on drug-induced kidney toxicity. Kolaviron may therefore intervene in the cellular redox status and depression of membrane protein activities caused by KBrO(3)and other environmental carcinogens in the kidney.     

Kolaviron prevents carbendazim-induced steroidogenic dysfunction and apoptosis in testes of rats

The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200 mg/kg) singly or in combination with kolaviron (100 and 200 mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.     

Hypoglycaemic and hypolipidaemic effects of fractions from kolaviron, a biflavonoid complex from Garcinia Kola in streptozotocin-induced diabetes mellitus rats

In the search for natural hypoglycaemic agents as alternatives to synthetic ones that are expensive and not easily accessible, and to justify the use of Garcinia kola seeds in traditional African medicine to treat diabetes, the hypoglycaemic and hypolipidaemic effects of fractions from kolaviron (KV) (a Garcinia kola seed extract) were investigated in normal and streptozotocin (STZ)-diabetic rats. KV, a biflavonoid complex from Garcinia kola seed, was separated by thin-layer chromatography into three fractions; Fraction I (FI), Fraction II (FII) and Fraction III (FIII) with RF values of 0.48, 0.71 and 0.76, respectively. In normoglycaemic rats, KV, FI and FII administered at a dose of 100 mg kg(-1) body weight elicited significant (P < 0.05) hypoglycaemic activity within 4 h of oral administration. Precisely, KV, FI and FII decreased blood glucose levels of normoglycaemic rats by 66%, 50% and 61%, respectively, when compared with controls 30 min after oral administration of the extracts. In hyperglycaemic rats, KV, FI and FII significantly (P < 0.05) reduced blood sugar levels in STZ-diabetic rats within 4 h of oral administration. Furthermore, KV alone produced a significant (P < 0.05) anti-diabetic effect from day 3 to day 7 of oral intubation of STZ-diabetic rats. In addition, the extracts showed favourable effect on the plasma lipid profile of STZ-diabetic rats, and also decreased significantly (P < 0.05) the STZ-induced increase in the activity of microsomal glucose-6-phosphatase and lipid peroxidation (LPO) products. This study confirms the anti-diabetic and hypolipidaemic effects of KV in STZ-diabetic rats. These observed effects of KV are attributed to two of its fractions, FI and FII, with RF values of 0.48 and 0.71, respectively.     

Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium

In this study, the morphological and biochemical susceptibility of the rat brain to vanadium, in the form of sodium metavanadate, and the comparative ameliorative effect of Garcinia kola and kolaviron (G. kola extract), was examined. Brain regions examined were the cerebrum, cerebellum, hippocampus and the olfactory bulb. We showed that vanadium administration caused cellular vacuolation, congestion, and Purkinje cell degeneration and a marked reduction in myelin tracts. Biochemical tests revealed increased lipid peroxidation induced by vanadium, which was ameliorated with the administration of G. kola and kolaviron. Vanadium administration caused an increase in thiobarbituric acid-reactive substances (TBARS) in the cerebrum and hippocampus, whereas the administration of kolaviron resulted in a reduction of the TBARS level by 65.7 and 80%, respectively, in the regions aforementioned. Also, the administration of kolaviron resulted in an increased activity of superoxide dismutase (61.24%) in all brain regions assessed, when compared with the group administered vanadium alone. Results obtained from this study led to the conclusion that kolaviron reduces vanadium-induced oxidative stress in the brain.     

Curcumin and kolaviron ameliorate di-n-butylphthalate-induced testicular damage in rats

The present study was carried out to evaluate the ameliorative effects of kolaviron (a biflavonoid from the seeds of Garcinia kola) and curcumin (from the rhizome, Curcuma longa L.) on the di-n-butylphthalate (DBP)-induced testicular damage in rats. Administration of DBP to rats at a dose of 2 g/kg for 9 days significantly decreased the relative testicular weights compared to the controls, while the weights of other organs remained unaffected. Curcumin or kolaviron did not affect all the organ weights of the animals. While only DBP treatment significantly increased the testicular malondialdehyde level and gamma-glutamyl transferase activity (gamma-GT), it markedly decreased glutathione level, the testicular catalase, glucose-6-phosphate dehydrogenase, superoxide dismutase, sperm gamma-GT activities and serum testosterone level compared to the control group. Data on cauda epididymal sperm count and live/dead ratio were not significantly affected in the DBP-treated rats. Alone, DBP treatment resulted in a 66% decrease in spermatozoa motility and a 77% increase in abnormal spermatozoa in comparison to control. DBP-treated rats showed marked degeneration of the seminiferous tubules with necrosis and defoliation of spermatocytes. The DBP-induced injuries in biochemical, spermatological parameters and histological structure of testis were recovered by treatment with kolaviron or curcumin. The pattern in the behaviour of these compounds might be correlated with their structural variations. Our results indicate that kolaviron and curcumin protect against testicular oxidative damage induced by DBP. The chemoprotective effects of these compounds may be due to their intrinsic antioxidant properties and as such may prove useful in combating phthalate-induced reproductive toxicity.     

Morphological and biochemical investigation into the possible neuroprotective effects of kolaviron (Garcinia kola bioflavonoid) on the brains of rats exposed to vanadium

In this study, the morphological and biochemical susceptibility of the rat brain to vanadium, in the form of sodium metavanadate, and the comparative ameliorative effect of Garcinia kola and kolaviron (G. kola extract), was examined. Brain regions examined were the cerebrum, cerebellum, hippocampus and the olfactory bulb. We showed that vanadium administration caused cellular vacuolation, congestion, and Purkinje cell degeneration and a marked reduction in myelin tracts. Biochemical tests revealed increased lipid peroxidation induced by vanadium, which was ameliorated with the administration of G. kola and kolaviron. Vanadium administration caused an increase in thiobarbituric acid–reactive substances (TBARS) in the cerebrum and hippocampus, whereas the administration of kolaviron resulted in a reduction of the TBARS level by 65.7 and 80%, respectively, in the regions aforementioned. Also, the administration of kolaviron resulted in an increased activity of superoxide dismutase (61.24%) in all brain regions assessed, when compared with the group administered vanadium alone. Results obtained from this study led to the conclusion that kolaviron reduces vanadium-induced oxidative stress in the brain.     

Commonly consumed and naturally occurring dietary substances affect biomarkers of oxidative stress and DNA damage in healthy rats.

The influence of black currant juice, Bowman-Birk protease inhibitor (BBI), kolaviron (a biflavonoid fraction of Garcinia kola seed), sugars, vitamin C and tert-butyl hydroperoxide on a wide range of biomarkers for oxidative stress, DNA damage and sugar or lipid metabolism has been investigated in male F 344 rats. The selected pro-oxidant control, tert-butyl hydroperoxide, significantly increased plasma and liver 2-amino-adipic semialdehyde (AAS), a marker of protein oxidation (p <0.05) whereas lipid oxidation assessed as malon dialdehyde (MDA) and DNA oxidation were not significantly increased. Feeding BBI also increased the level of oxidized protein in plasma and liver at the higher dose level (0.5%). No effect was observed at the lower dose level (0.25%), which even decreased lipid oxidation in plasma. BBI did not affect background levels of DNA strand breaks or oxidation (comets). In rats exposed to black currant juice, a statistically significant decrease in liver AAS and MDA was observed. This effect could not be explained by its content of sugars or of the known redox active constituent, vitamin C. The lowering effect of black currant juice on protein and lipid oxidation was similar in magnitude to that of the known liver protectant, kolaviron. In rats treated with kolaviron (200 mg/kg body weight), background AAS levels were significantly reduced in both plasma and liver whereas the effect on MDA only reached statistical significance in plasma. Kolaviron was the only extract tested which decreased oxidative damage to DNA in the liver. The erythrocyte antioxidant enzyme activities, catalase and glutathione peroxidase were decreased in rats treated with tert-butyl hydroperoxide (p <0.05) but were not affected by the other treatments. Black currant juice and sugars increased plasma triglyceride levels and black currant juice increased plasma cholesterol but neither of them nor any other treatment affected blood glucose, erythrocyte HbA1c or fructosamine. We conclude that markers of oxidative stress may be modified by several mechanisms after feeding rats with complex dietary factors and that both pro- and antioxidant effects may consequently be observed simultaneously after short-term feeding of antioxidant-rich foods, herb medicines, or known pro- and antioxidants.     

Chemoprotection of ethylene glycol monoethyl ether-induced reproductive toxicity in male rats by kolaviron, isolated biflavonoid from Garcinia kola seed

The present study investigated the protective effect of kolaviron, a biflavonoid from the seed of Garcinia kola, on ethylene glycol monoethyl ether (EGEE)-induced reproductive toxicity in male rats. The protective effect of kolaviron was validated using vitamin E, a standard antioxidant. EGEE was administered at a dose of 200 mg/kg. Other groups of rats were simultaneously treated with kolaviron (100 and 200 mg/kg) and vitamin E (50 mg/kg) for 14 days. EGEE treatment resulted in significant decrease in glutathione (GSH) level, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities but markedly increased the glutathione-S-transferase (GST) and lactate dehydrogenase (LDH) activities in the testes. In the spermatozoa, administration of EGEE caused significant decrease in the activities of CAT, GPx, GST and LDH as well as in the level of GSH but significantly increased SOD activity with concomitant increase in hydrogen peroxide and malondialdehyde levels in both testes and spermatozoa. EGEE-exposed rats showed marked testicular degeneration with concomitant decrease in spermatozoa quantity and quality. Overall, EGEE causes reproductive dysfunction in rats by altering antioxidant systems in the testes and spermatozoa. Kolaviron or vitamin E exhibited protective effects against EGEE-induced male reproductive toxicity by enhancement of antioxidant status and improvement in spermatozoa quantity and quality.     

Anti-oxidant mechanisms of kolaviron: studies on serum lipoprotein oxidation, metal chelation and oxidative membrane damage in rats

1. In the present study, we have examined the ability of kolaviron, a natural biflavonoid from Garcinia kola seeds, to prevent the susceptibility of rat serum lipoprotein to undergo oxidative modification in vitro and ex vivo. In addition, its ability to chelate metal ions and mitigate iron/ascorbate-induced damage to microsomal lipids was investigated. 2. Lipoprotein resistance to copper-induced oxidation was highly improved in rats treated with kolaviron (100 mg/kg) for 7 days, as demonstrated by a significant increase in lag time compared with control. A significant (P < 0.05) decrease in area under the curve (AUC) and slope of propagation was observed in kolaviron-treated rats compared with control. Conjugated dienes formed after 240 min of lipoprotein oxidation were markedly decreased in kolaviron-treated rats compared with controls. Malondialdehyde concentrations were significantly reduced in the serum lipoproteins of kolaviron-treated rats with an attendant significant increase in the total anti-oxidant activity compared with control. 3. In vitro, kolaviron (10-60 micromol/L) inhibited the Cu2+-induced oxidation of rat serum lipoprotein in a concentration-dependent manner. Kolaviron, at 20 and 60 micromol/L, produced 48 and 87% inhibition of oxidation of lipoprotein, respectively. Compared with control, kolaviron, at 10 and 20 micromol/L, resulted in 29 and 47% decreases in AUC, respectively. In addition, kolaviron (10 micromol/L) elicited a 53% increase in lag time, whereas 40 and 60 micromol/L kolaviron produced 38 and 88% decreases in slope, respectively. 4. Kolaviron effectively prevented microsomal lipid peroxidation induced by iron/ascorbate in a concentration-dependent manner. Kolaviron at the highest dose tested (90 micromol/L) had a significant chelating effect on Fe2+ (78%). 5. In conclusion, our data demonstrate that kolaviron protects against the oxidation of lipoprotein, presumably by mechanisms involving metal chelation and anti-oxidant activity, and, as such, may be of importance in relation to the development of atherosclerosis.     

The protective effect of taurine against cyclosporine A-induced oxidative stress and hepatotoxicity in rats

Cyclosporine A (CsA) is the immunosuppressor which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been implicated as one of the possible mechanisms of CsA-induced hepatotoxicity. The present investigation examined the ability of taurine as an antioxidant to protect against CsA-induced oxidative stress and hepatotoxicity. CsA hepatotoxicity was induced by subcutaneous injection of CsA at a dose of 20mg/kg body weight daily for 21 days. Hepatotoxicity was assessed by reduced serum total protein level and increased serum levels of gamma glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransaminase (AST). CsA treatment increased lipid peroxidation measured as thiobarbituric acid reactive substances (TBARS) concentration and decreased reduced glutathione (GSH) content and activities of catalase and glutathione peroxidase (GSH-Px) in the rat liver. Taurine administration (1% in the drinking water) for 3 days before and concurrently during CsA injections improved liver functions, as indicated by decline of serum transaminases and GGT levels and elevation of serum total protein. Moreover, taurine significantly reduced hepatic TBARS and increased GSH content and catalase and GSH-Px activities in the hepatic tissue. These results indicate that taurine has a protective action against CsA hepatotoxicity and suggest that taurine may find clinical application against a variety of toxins where cellular damage is a consequence of reactive oxygen species.     

Protective effects of syringic acid against acetaminophen-induced hepatic damage in albino rats

The protective effect of the phenolic compound syringic acid, one of the major benzoic acid derivatives from edible plants and fruits, was evaluated against acetaminophen (APAP)-induced hepatotoxicity in rats. Toxicity was induced in adult male albino Wistar rats by the administration of APAP (750 mg/kg body weight) intraperitoneally. Rats were treated with syringic acid (25, 50, and 100 mg/kg body weight) by the oral route. We assessed the activity of hepatic markers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and bilirubin. Lipid peroxidative markers thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides, and a decrease in enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and non-enzymatic antioxidants vitamin C, vitamin E and reduced glutathione levels. Liver histology also showed convincing evidence regarding their protective nature against fatty changes induced during APAP intoxication. Syringic acid administered at a dose of 50 mg/kg body weight significantly decreased the activities of hepatic and renal function markers to near normal values when compared with the other two doses. The results suggest that syringic acid could afford a significant protective effect against APAP induced hepatic damage in rats.     

Protective effect of diphenyl diselenide on acute liver damage induced by 2-nitropropane in rats

The effect of diphenyl diselenide, (PhSe)2, administration on 2-nitropropane (2-NP)-induced hepatic damage was examined in male rats. Rats were pre-treated with a single dose of diphenyl diselenide (10, 50 or 100 micromol/kg). Afterward, they received only one dose of 2-NP (100 mg/kg body weight dissolved in olive oil). The parameters that indicate tissue damage such as plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alpha-fetoprotein (AFP), creatinine and urea were determined. Since toxicity induced by 2-NP is related to oxidative stress, lipid peroxidation was also evaluated. Diphenyl diselenide (100 micromol/kg) significantly reduced plasma ALT, gamma-GGT, AFP levels when compared to 2-NP group. Treatment with diphenyl diselenide, at all doses, effectively protects the increase of lipid peroxidation when compared to 2-NP group. Histological examination revealed that 2-NP treatment causes a moderate swelling and degenerative alterations on hepatocytes and diphenyl diselenide (100 micromol/kg) protects against these alterations. Diphenyl diselenide (50 and 100 micromol/kg) significantly decreased the urea level. This study evidences the protective effect of diphenyl diselenide by 2-NP-induced acute hepatic damage.     

Kolaviron prevents ethylene glycol monoethyl ether-induced testicular apoptosis via down-regulation of stress proteins,Fas/Fas-L and caspases expressions in rats

Abstract

This study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200?mg/kg) separately or in combination with either kolaviron (100 or 200?mg/kg) or vitamin E (50?mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L, was accompanied by nuclear factor kappa B downregulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. In addition, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.     

Effect of Garcinia cambogia extract on lipids and lipoprotein composition in dexamethasone administered rats

Dexamethasone (10 mg/kg body weight/day, s.c.) administered rats were treated with or without Garcinia cambogia fruit extract (1 g/kg body weight/day, orally) for 8 days. The administration of dexamethasone resulted in marked increase in the levels of triglycerides and cholesterol and free acids in both plasma and liver. The level of phospholipids increased in the plasma but decreased significantly in liver tissue after dexamethasone administration as compared to those in normal rats. The activities of lecithin cholesterol acyl transferase and hepatic lipoprotein lipase were lowered significantly after dexamethasone per se administration. The levels of HDL-triglycerides and HDL-cholesterol remained unchanged, while the LDL and VLDL increased significantly in dexamethasone administered rats. The lipid levels were maintained at near normalcy when co-treated with Garcinia cambogia extract in dexamethasone administered rats. This study reveals the undesirable changes in lipid profile on dexamethasone administration and the hypolipidemic property of Garcinia cambogia extract.     

Toxicity and metabolism of a new insect repellent N,N-diethylphenylacetamide in mice, rats and guinea pigs on cutaneous application

Cutaneous LD50 of N,N-diethylphenylacetamide (DEPA), a new multi insect repellent was 2200, 3200 and 7100 mg/kg body weight in female mice, rats and guinea pigs; and 1600 and 4000 mg/kg in male mice and rats indicating a high degree of safety on skin contact. Dermal application of DEPA to young growing rats for 21 days at a dose of 50 mg/kg did not exert any adverse effects while massive doses of 500 and 1000 mg/kg caused marked reduction of body weight gain and lowering of activities of serum alanine aminotransferase, aspartate aminotransferase and cholinesterase. Along with DEPA, N-ethylphenylacetamide, phenylacetamide and phenylacetic acid were detected in the urine of DEPA treated mice, rats and guinea pigs.     

Disposition of single oral doses of butylated hydroxyanisole in man and rat

The kinetics and metabolism of butylated hydroxyanisole (BHA) have been compared between man and rats. Oral doses of 2, 20 or 200 mg BHA/kg body weight were administered to male Wistar rats and a single oral dose of 0.5 mg/kg body weight was administered to human volunteers (non-smoking males). Following oral administration of 2 or 20 mg BHA/kg body weight to rats, no plasma BHA profiles were observed, whereas at the 200 mg BHA/kg body weight dose level plasma BHA peak concentrations between 100 and 400 ng/ml were detected. Plasma BHA peak levels and the area under the curve show that the application of 15% polyethylene glycol-400 as the vehicle produced significantly lower values compared with those obtained using the vehicles, salad dressing, corn oil and dimethylsulphoxide. In man, oral administration of 0.5 mg BHA/kg body weight dissolved in corn oil gave plasma BHA peak concentrations of greater value than 100 ng/ml (range 53 to 255 ng/ml). In rats, 24 hr after dosing 2, 20 or 200 mg BHA/kg body weight the mean BHA concentrations in adipose tissue ranged from 0.7 to 6.8 micrograms/g. In man and rats, BHA was O-demethylated to tert-butylhydroquinone (TBHQ). This is the first study to report that TBHQ is an in vivo metabolite of BHA in rats. Within 4 days following oral administration the total recovery of BHA in the urine and faeces of man (0.5 mg BHA/kg body weight) and rats (200 mg BHA/kg body weight) was 49 +/- 7% and 95 +/- 10% (mean +/- SD) respectively. In rats, BHA was excreted in the urine as free BHA (2%), conjugated BHA (48%) and conjugated TBHQ (9%) and in the faeces as free BHA (36%). In man, BHA was excreted in the urine mainly as conjugated BHA (39%) together with smaller amount of conjugated TBHQ (9%); no free BHA was found in the urine or faeces. In man and rats only the fraction of BHA excreted in urine as conjugates of BHA and TBHQ was qualitatively and quantitatively comparable. Results in this study indicate a considerable difference in the biological fate of BHA following oral administration of high and low doses of BHA in rat and man, respectively.