Cerium oxide nanoparticle elicits oxidative stress, endocrine imbalance and lowers sperm characteristics in testes of balb/c mice.

The toxicity of metallic nanoparticles is a growing concern due to its application in industries and homes. We investigated the toxicity of cerium oxide nanoparticles (CeO2 NPs) on reproductive system in male balb/c mice. Twenty mice were divided into four groups of five animals each and treated thus: normal saline (control), 100, 200 and 300 µg/kg CeO2 NPs (i.p.,) thrice in a week for five consecutive weeks. Results showed that CeO2 NPs significantly reduced the levels of haemoglobin, PCV and RBC count relative to controls. In addition, luteinising and follicle-stimulating hormones (FSH and LH) and prolactin were significantly reduced in the mice. Specifically, CeO2 NPs at 100 µg/kg decreased testosterone by 23%, while CeO2 NPs at 200 µg/kg decreased FSH, LH and prolactin by 25%, 26% and 13%, respectively. Testicular malondialdehyde was increased by 103%, 106% and 135% in mice treated with 100, 200 and 300 µg/kg CeO2 NPs, respectively. CeO2 NPs caused a significant reduction in activities of antioxidant enzymes and levels of reduced glutathione and total nitric oxide. Moreso, CeO2 NPs decreased sperm motility and count and increased total sperm abnormality in mice. Histology revealed congestion and degeneration of seminiferous tubules. Overall, CeO2 NPs induces testicular dysfunction via disruption of antioxidant/oxidant balance and endocrine suppression.

Changes in the brain antioxidant profile after chronic vanadium administration in mice.

Vanadium is known to induce reactive oxygen species (ROS) in biological systems. Exposure to vanadium has been linked to neurological defects affecting the central nervous system (CNS) early in life and culminates later to neurodegeneration. This study was designed to evaluate the effects of chronic vanadium exposure on antioxidant profile in mice, and progressive changes after withdrawal from treatment. A total of 85 male BALB/c mice (4 weeks old) were used for the experiment and were divided into three groups of vanadium exposed (3 mg/kg i.p at 3-18 months treatment), matched controls, and animals exposed to vanadium for three months and thereafter vanadium was withdrawn. Vanadium exposure caused significant increases (p<0.05) in levels of malondialdehyde (MDA), hydrogen peroxide (H2O2) generation and nitric oxide with a concomitant decrease (p<0.05) in the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione-S-transferase and a decline in the level of reduced glutathione (GSH) after 6 months of vanadium exposure in the brain. This trend continued in all vanadium-exposed groups (9, 12, 15 and 18 months) relative to the matched controls. Withdrawal after 3 months of vanadium exposure significantly reversed oxidative stress in intoxicated mice from 9 to 15 months after vanadium withdrawal. We have shown that chronic administration of vanadium led to oxidative stress in the brain which is reversible only after a long period of vanadium withdrawal.

Modulatory role of betulinic acid in N-nitrosodimethylamine-induced hepatorenal toxicity in male Wistar rats.

N-nitrosodimethylamine (NDMA) is a toxicant found in foods and drinking water. Several synthetic agents used in alleviation of NDMA toxicity have been associated with serious side effects. Therefore, a safe and less toxic agent is desirable. In this study, betulinic acid (BA), a triterpenoid antioxidant, is proposed as a better and alternative agent to modulate NDMA-induced toxicity. Twenty-four Wistar rats were assigned into four groups of six rats each and treated with normal saline (control), BA (25 mg/kg), NDMA (5 mg/kg) and (BA + NDMA). BA was given by oral gavage for 14 consecutive days, while NDMA was administered intraperitoneally on days 7 and 12. Results showed that administration of NDMA significantly ( p < 0.05) elevated the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase and gamma-glutamyl transferase by 51%, 48% and 81%, respectively. Also, NDMA intoxication significantly ( p < 0.05) increased the levels of serum urea and creatinine by 64% and 82%, respectively, and decreased urinary creatinine by 67%. In addition, administration of NDMA significantly ( p < 0.05) increased the levels of hepatic and renal DNA fragmentation by 44% and 61%, respectively, relative to control. The number of micronucleated polychromatic erythrocytes (mnPCEs) in NDMA-treated rats (11.1 ± 2.6 mnPCE/1000PCE) was significantly higher than control (4.3 ± 1.1 mnPCE/1000 PCE). Immunohistochemistry revealed strong expressions of Bcl-2 and nuclear p53 in NDMA-intoxicated rats. Interestingly, pretreatment with BA significantly ( p < 0.05) ameliorated NDMA-induced changes in serum biochemical indices, mnPCEs, DNA fragmentation and expressions of Bcl-2 and p53 proteins. These findings suggest that BA protects against NDMA-induced toxicity via anti-oxidative and anti-apoptotic activities.

Protective effects of Artocarpus altilis (Moraceae) on cadmium-induced changes in sperm characteristics and testicular oxidative damage in rats.

Cadmium (Cd) is a major environmental toxicant and an endocrine disruptor. We investigated the protective effects of methanol extract of Artocarpus altilis (AA) against Cd-induced testicular damage in rats while quercetin (Que) served as standard. The total flavonoids and phenolic contents (TFC and TPC), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and hydroxyl (OH) radicals scavenging activities of AA were determined. In vivo, thirty male Wistar rats were assigned to six groups and orally treated with corn oil (control), Cd alone, Cd+Que, Cd+AA, Que and AA alone. Que and AA were given at doses of 25 and 200 mg kg(-1), respectively, for 3 weeks and challenged with two doses of Cd (1.5 mg kg(-1)). Results showed that TFC and TPC of AA increased with increase in concentration. AA scavenged DPPH and OH radicals in a dose-dependent manner. Administration of Cd significantly increased the relative weight of testis of rats. Lipid peroxidation was significantly increased while antioxidant parameters decreased in testis of Cd-treated rats. Also, Cd-treated rats had significantly reduced sperm count, motility, sialic acid, luteinising hormone and testosterone relative to controls. Pre-treatment with AA or Que significantly attenuated the biochemical alterations observed in Cd-treated rats. Overall, AA protects against Cd-induced testicular damage via antioxidative mechanism.

Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on the antioxidant, hormonal and spermatogenic indices of diabetic male rats.

The antihyperglycaemic effect of kolaviron (KV), a biflavonoid from Garcinia kola has been established in previous studies. In this study, we investigated the effect of KV (200 mg kg(-1) ) on the antioxidant, hormonal and spermatogenic indices of alloxan-diabetic male rats, and metformin hydrochloride (MET) (30 mg kg(-1) ) served as standard drug. The results showed that KV and MET significantly (P < 0.05) decreased the fasting blood glucose of the diabetic rats. Also, untreated and MET-treated diabetic groups had significantly (P < 0.05) lower body-weight gain and relative weights of testes. In addition, epididymal sperm abnormalities were increased, whereas sperm count, motility, testicular protein and sialic acid were decreased in untreated diabetic group. Also, antioxidant parameters, reduced glutathione, catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase were significantly (P < 0.05) reduced in the testes with a concomitant increase in lipid peroxidation in untreated diabetic group. Furthermore, untreated diabetic group had significantly (P < 0.05) lower levels of testosterone, luteinising and follicle-stimulating hormones relative to controls. Treatment with KV restored the relative weights of testes, activities of antioxidant enzymes, sperm and hormonal indices of the diabetic animals. This study demonstrated the role of KV to promote fertility in diabetic male rats by enhancing the hormonal and antioxidant status of the rats.

A Comparative In Vitro Study on the Antioxidant and Anti-acetylcholinesterase Properties of Aerial Parts of Strophanthus preusii Engl & Pax.

OBJECTIVE: To evaluate and compare the antioxidant and acetylcholinestrase (AChE)-inhibitory properties of aerial parts of Strophanthus preussii (leaves, stem and root named as SPL, SPS and SPR, respectively) while catechin served as standard. METHODS: The antioxidant and AchE-inhibitory properties of the methanol extracts of SP were evaluated by standard in vitro methods viz: DPPH (2,2-diphenyl-1-picrylhydrazine), nitric oxide (NO), hydroxyl radical (OH-) and hydrogen peroxide (H2O2) radical scavenging assays as well as reducing power, Fe2+/ascorbate-induced lipid peroxidation (LPO) and AChE inhibition assays. The total phenolic and flavonoid contents of the extracts were also estimated. RESULTS: High phenolic and flavonoid contents were found in the aerial parts of Strophanthus preussii. The amount of phenolic and flavonoids contents followed the order SPL > SPR > SPS at 250─1000 µg/ml. The results revealed that all the extracts showed antioxidant activities in vitro. However, SPL had the highest DPPH, H2O2 and OH radical scavenging abilitie, while the reducing power of the extracts followed the order SPR > SPL > SPS at 1000 µg/ml. In addition, SPL, SPS and SPR significantly inhibited LPO in rat liver by 42%, 23%, 35% and in rat brain by 68%, 31% and 51%, respectively. The LPO inhibitory activities of SPL were statistically similar to the standard. Only SPS produced significant NO scavenging effects among the extracts. The percentage inhibition of AChE activity was significant for SPL and SPR at 750 and 1000 µg/ml. CONCLUSION: The leaves and root of Strophanthus preusii proved to be potent natural antioxidants and could justify their traditional use in the management of stress-related diseases.

Effect of moderate ethanol administration on biochemical indices in streptozotocin-diabetic Wistar rats.

OBJECTIVE: This study was designed to evaluate the effect of moderate ethanol administration on the biochemical indices in streptozotocin (STZ)-diabetic rats. METHODS: Twenty-four male Wistar rats were divided into four groups of six animals each. Groups one and two contained non-diabetic normal rats and normal rats treated with ethanol, respectively. Group three was untreated STZ-diabetic rats and group four was made up of ethanol-treated STZ-diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (35 mg/kg), while ethanol (100%v/v) was given at a dose 2 g/kg thrice per week for three weeks. After the last dose of ethanol and an overnight fasting, rats were sacrificed by cervical dislocation. Blood was collected by syringe from the heart into plain centrifuge tubes. RESULTS: Moderate ethanol administration to STZ-diabetic rats caused a significant (p < 0.05) increase in relative weight of liver relative to normal. Ethanol intake in STZ-diabetic rats produced an insignificant (p > 0.05) effect on the levels of fasting blood glucose (FBG) and HbA1c relative to the untreated-diabetic group. Moderately, ethanol administration to STZ-diabetic rats produced a marked and significant (p < 0.05) increase in the levels of serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol and the activities of alanine aminotransferase relative to untreated diabetic rats. Ethanol-treated diabetic rats had significantly (p < 0.05) lower high-density lipoprotein (HDL)-cholesterol levels, while the activities of lactate dehydrogenase and alpha-amylase were insignificantly (p > 0.05) affected. There were no significant (p > 0.05) differences in all the biochemical indices in normal rats relative to ethanol-treated normal rats. CONCLUSIONS: Moderate ethanol administration did not affect FBG and HbA1c, but altered the lipid profile of STZ-diabetic rats. Moderate ethanol intake may further increase the risk of complications in diabetes.

Antidiabetic effect of kolaviron, a biflavonoid complex isolated from Garcinia kola seeds, in Wistar rats.

BACKGROUND: Hypoglycaemic effect of kolaviron (KV), (biflavonoid from Garcinia kola) in streptozotocin (STZ)-diabetic rats has been established. OBJECTIVES: To evaluate the possible protective effects of KV on cardiac, renal and hepatic tissues of STZ-diabetic rats. METHODS: This study consists of four groups of 6 rats each. Groups one and two contained non-diabetic and untreated-diabetic rats, respectively. Groups three and four were made up of KV- and glibenclamide (GB) - treated diabetic rats, respectively. RESULTS: STZ-intoxication caused a significant (p<0.05) increase in the relative weight of liver in diabetic rats. STZ-diabetic rats had significant increase (p<0.05) in the levels of fasting blood glucose (FBG), á-amylase and HbA1c. A marked and significant (p<0.05) increase in the levels of cardiac, renal and liver marker indices such as serum creatine kinase, lactate dehydrogenase, creatinine, urea and alanine aminotransferase were observed in untreated diabetic rats. Also, untreated diabetic rats had significantly (p<0.05) elevated urinary glucose and protein and, lowered creatinine clearance. In KV- and GB- treated groups, the levels of FBG, á-amylase and HbA1c were significantly (p<0.05) reduced, while treatment with KV significantly (p<0.05) attenuated the cardiac, renal and liver marker indices. CONCLUSION: KV offered significant antidiabetic and tissues protective effects in the rats.

Trace elements and vitamin E status in Nigerian patients with prostate cancer.

BACKGROUND: Prostate cancer is the most common type of cancer among men. OBJECTIVES: To investigate the trace elements (Se, Zn, Cu and Cd) and vitamin E status of some Nigerian prostate cancer (PCa) patients relative to their prostate-specific antigen (PSA) values. METHODS: Prostate cancer patients were assigned into groups 1, 2 and 3 with PSA of 5-10 ng/ml, 11-20 ng/ml and > 20 ng/ml, respectively. RESULTS: The results showed that the levels of whole blood superoxide dismutase (SOD) and serum Se and Zn were significantly lower (p< 0.05) in the PCa patients. Specifically, levels of SOD, Se and Zn decreased by 67%, 30% and 35%; 70%, 52% and 41%; 81%, 58% and 47%, in subjects with PSA of 5-10 ng/ml, 11-20 ng/ml and > 20 ng/ml, respectively. There were no significant differences (p> 0.05) in levels of Cu and Cd. Serum Cu/ Zn ratio were significantly higher in PCa patients. The Cu/ Zn ratios were 1: 1.2: 1.3 for subjects in groups 1, 2 and 3, respectively. Vitamin E levels in PCa patients were significantly lower and followed the order; normal > PSA (5-10) > PSA (11-20) > PSA (> 20). CONCLUSIONS: Deficiency of vitamin E, Zn and Se may be risk factors for development of PCa.

Effects of Xylopia aethiopica (Annonaceae) fruit methanol extract on gamma-radiation-induced oxidative stress in brain of adult male Wistar rats.

Xylopia aethiopica (XA) (Annonaceae) possesses great nutritional and medicinal values. This study was designed to investigate the effects of XA fruit methanol extract on oxidative stress in brain of rats exposed to whole body gamma-radiation (5 Gy). Vitamin C (VC) served as standard antioxidant. Forty-four rats were divided into 4 groups of 11 rats each. One group served as control, two different groups were treated with XA and VC (250 mg/kg), 6 weeks before and 8 weeks after irradiation, and fourth group was only irradiated. Rats were sacrificed 1 and 8 weeks after irradiation. The antioxidant status, viz. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST) and glutathione (GSH) were estimated. Results indicate a significant increase (p < 0.05) in levels of brain LPO after irradiation. LPO increased by 90% and 151%, after 1 and 8 weeks of irradiation, respectively. Irradiation caused significant (p < 0.05) decreases in levels of GSH and GST by 61% and 43% after 1 week and, 75% and 73%, respectively, after 8 weeks of exposure. CAT and SOD levels were decreased by 62% and 68%, respectively, after 8 weeks of irradiation. Treatment with XA and VC ameliorated the radiation-induced decreases in antioxidant status of the animals. These suggest that XA could have beneficial effect by inhibiting oxidative damage in brain of exposed rats.

Hepatoprotective effect of Curcuma longa L. in D-galactosamine induced liver injury in mice: evidence of antioxidant activity.

The aim of this study was to investigate the hepatoprotective effect of methanolic extract of Curcuma longa L (CLME) in D-galactosamine (GNH2) induced liver injury and the mechanism(s) involved. The ability of vitamin C (VC) to attenuate the toxicity was also examined. Mice were pretreated with CLME and VC at a dose of 100-mg/kg per oral for seven consecutive days before challenge with a dose of GNH2 (800 mg/kg i.p.). Integrity of liver from the animals was assessed by determining the levels of serum alanine and aspartate aminotransferases (ALT and AST) and alkaline phosphatase (ALP). The antioxidant status was monitored by the levels of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione (GSH) and malondialdehyde (MDA) (Lipid peroxidation (LPO) index). GNH2 treatment markedly increased the levels of serum ALT and AST, which were significantly (p<0.05) attenuated in animals pretreated with CLME and VC. Also, CLME significantly (p<0.05) increased the levels of hepatic GST and SOD, with a concomitant marked reduction in the levels of hepatic and serum LPO in the GNH2-challenged mice. Furthermore, hepatic GSH which was decreased after GNH2 intoxication, was significantly (p<0.05) enhanced by cotreatment with CLME and VC. However, there were no significant differences (p>0.05) in the levels ofALP and CAT of these animals. The liver histopathology results revealed that GNH2-induced injury was prevented in mice co-treated with VC and CLME. The results suggest that the hepatoprotective effect of CLME in GNH2 induced liver injury may be related to its antioxidant activity.

Comparative effects of vitamin E and kolaviron (a biflavonoid from Garcinia kola) on carbon tetrachloride-induced renal oxidative damage in mice.

It became evident in this study that carbon tetrachloride (CCl4), can induce renal oxidative damage. The hepatoprotective effects of vitamin E (Vit. E) and kolaviron (KV), a biflavonoid complex from the seeds of Garcinia kola are well documented. The present study was designed to investigate and compare the renal protective effects of Vit. E and KV in mice given CCl4 (1.2 g kg(-1)) intra-peritoneally thrice a week for two weeks. CCl4 caused a marked increase in serum and renal lipid peroxidation (LPO) by 106 and 225%, respectively. Treatment with KV at 100 and 200 mg kg(-1) and Vit. E at 100 mg kg(-1) significantly (p < 0.05) decreased the CCl4-mediated increase in LPO. Furthermore, CCl4-intoxication decreased the levels of renal reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) by 44, 56 and 43%, respectively. Treatment with KV and Vit. E significantly (p < 0.05) ameliorated the GSH and SOD levels. Specifically, KV at 100 and 200 mg kg(-1) increased GSH by 32 and 27% and SOD levels by 50 and 53%, respectively. Likewise, treatment with Vit. E increased GSH and SOD levels by 31 and 53%, respectively. Effects on markers of renal functions showed that CCl4-intoxication significantly (p < 0.05) elevated serum urea and creatinine by 287 and 186%, respectively. While treatment with Vit. E decreased serum urea and creatinine by 60 and 55%, respectively, KV produced insignificant (p > 0.05) effect on these parameters. This study found KV unable to protect against CCl4-induced renal damage but confirmed the potency of Vit. E to enhance recovery from renal oxidative damage.

Effect of kolaviron, a biflavonoid complex from Garcinia kola seeds, on ethanol-induced oxidative stress in liver of adult wistar rats.

The role of oxidative stress in the pathogenesis of alcoholic diseases in the liver is well documented. Kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, possesses a variety of biological activities, including antioxidant. Our aim was to investigate in vivo whether KV may attenuate oxidative stress in liver of Wistar albino rats following chronic ethanol administration. Thirty-six male Wistar albino rats were randomly divided into six groups. Toxicity was induced by administering 7.5% or 45% ethanol at 3 g/kg of body weight daily for 8 weeks. Rats were treated with KV at 200 mg/kg of body weight for the same duration. Treatment was by oral gavage. Integrity of liver was assessed by determining the levels of serum alanine and aspartate aminotransferases (ALT and AST, respectively) and alkaline phosphatase (ALP). The antioxidant status was monitored by determining the levels of hepatic superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), and malondialdehyde (MDA), the end product of lipid peroxidation (LPO). Experimentally, chronic ethanol administration led to hepatotoxicity as evidenced by the increase in levels of serum ALT, AST, and ALP. Ethanol also enhanced the formation of MDA in the liver. Specifically, MDA was elevated by 70% and 98% in animals treated with 7.5% and 45% ethanol, respectively. Levels of hepatic SOD, CAT, GST, and GSH were significantly (P < .05) reduced by ethanol treatment. Co-administration of KV during ethanol treatment inhibited hepatic LPO and ameliorated SOD and GST activities. These findings demonstrated that KV could have a beneficial effect by inhibiting the oxidative damage in liver of Wistar rats caused by chronic ethanol administration.

Hepatoprotective activity of purified fractions from Garcinia kola seeds in mice intoxicated with carbon tetrachloride.

The hepatoprotective activity of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds, and its purified fractions was investigated in mice intoxicated with carbon tetrachloride (CCl(4)). The ability of vitamin E to attenuate the toxicity was also examined. KV was extracted from powdered seeds of G. kola and then separated by thin-layer chromatography into three fractions--Fraction I (FI), Fraction II (FII), and Fraction III (FIII), with ratio of fronts values of 0.48, 0.71, and 0.76, respectively. Pretreatment with KV, FI, and FII at a dose of 100 mg/kg of body weight for 2 weeks and then challenge with CCl(4) at a dose of 1.2 g/kg of body weight, three times a week for 2 consecutive weeks, decreased the CCl(4)-induced increase in activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) by 31%, 30%, and 31% and 41%, 55%, and 42%, respectively. CCl(4) intoxication also caused a significant (P < .05) accumulation of lipid peroxidation (LPO) products as revealed by the formation of the thiobarbituric acid-reactive substances: CCl(4) induced LPO levels in serum and microsomes by 112% and 89%, respectively. However, pretreatment with KV, FI, and FII decreased LPO levels in serum by 31%, 41%, and 40% and in microsomes by 48%, 39%, and 35%, respectively. Vitamin E was protective in reducing the CCl(4)-induced increase in levels of AST, ALT, and gamma-glutamyl transferase as well as LPO. Furthermore, CCl(4) intoxication significantly (P < .05) decreased the activities of microsomal glucose-6-phosphatase, aniline hydroxylase, and cytosolic glutathione-S-transferase (GST). While pretreatments with KV, FI, and FII were able to ameliorate the levels of glucose-6-phosphatase and GST, there were no significant (P > .05) effects on the levels of aniline hydroxylase and DT-diaphorase. This study confirms that FI and FII from KV enhanced recovery from CCl(4)-induced hepatotoxicity by decreasing the extent of LPO and also inducing the levels of phase II enzyme (GST). These fractions are responsible for the observed antihepatotoxic effect of KV.

Hypolipidemic effect of Telfairia occidentalis (fluted pumpkin) in rats fed a cholesterol-rich diet.

Telfairia occidentalis (fluted pumpkin) is one of the commonly consumed leafy vegetables in Nigeria. In order to justify its inclusion in herbal preparations in African traditional medicine, the possible hypolipidemic effect of this vegetable was investigated in rats fed a cholesterol-rich diet. The ability of Questran, a hypolipidemic drug, to attenuate hypercholesterolemia was also examined. Rats were fed with either a basal diet containing cholic acid (0.2%) or a supplemented diet with T. occidentalis at the 3% and 6% levels. Oral administration of cholesterol for 9 consecutive weeks resulted in a significant increase (P < .001) in the relative weight of the heart of cholesterol-fed rats. However, supplemented diets significantly (P < .001) ameliorated the cholesterol-induced enlargement of the heart. Rats fed on supplemented diets had a dose-dependent reduction in plasma and postmitochondrial supernatant fraction (PMF) cholesterol levels. In particular, supplemented diets containing 3% and 6% T. occidentalis decreased plasma and PMF cholesterol levels by 20% and 30% and by 30% and 45%, respectively. A similar decrease in plasma and PMF cholesterol levels was obtained in Questran-treated hypercholesterolemic rats. Furthermore, 3% and 6% T. occidentalis-supplemented diets significantly (P < .05) decreased the cholesterol-induced increase in plasma and PMF low-density lipoprotein (LDL) cholesterol levels by 24% and 48% and by 28% and 52%, respectively. In contrast, there was no significant difference (P > .05) in plasma and PMF triglyceride levels of rats fed on supplemented diets when compared with cholesterol-fed rats. There were significant decreases (P < .05) in lipid peroxidation levels in rats fed on the supplemented diets. Specifically, 3% and 6% T. occidentalis-supplemented diets decreased plasma and PMF lipid peroxidation by 24% and 20% and by 42% and 21%, respectively. This study demonstrates that T. occidentalis may be a useful therapy for hypercholesterolemia through reducing oxidative stress and cholesterol levels.

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.

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.

Possible protective effect of kolaviron on CCl4-induced erythrocyte damage in rats.

The possible protective effect of kolaviron on rat erythrocytes following simultaneous administration of kolaviron (100 mg/kg of body weight/day) with carbon tetrachloride CCl4 (1.195 g/kg of body weight/day) by separate intraperitoneal injections was investigated. Kolaviron, a biflavonoid fraction of the defatted alcoholic extract of Garcinia kola seed, inhibits the accumulation of lipid peroxidation products in erythrocytes. A significant reduction (p < 0.05) by about 34%, of lipid peroxidation products was observed in erythrocytes of rats treated simultaneously with CCl4 and kolaviron when compared to CCl4-treated rats. Similarly, the significant increase (p < 0.05) in membrane cholesterol observed in CCl4-treated rats was significantly decreased (p < 0.05) in rats treated simultaneously with CCl4 and kolaviron. Therefore, there was no significant difference (p < 0.05) in cholesterol phospholipid ratio (C/P) of rats treated simultaneously with CCl4 and kolaviron, and the controls. Thus, kolaviron normalizes the CCl4-induced change in erythrocyte membrane composition. In addition, kolaviron antagonizes the effect of CCl4 on the activity of the membrane bound enzyme, Ca2+-ATPase. These results suggest that kolaviron protects erythrocyte membranes from free radical attack, on both lipids and proteins.