Oluwatosin A. Adaramoye

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.

Changes in antioxidant status and biochemical indices after acute administration of artemether, artemether-lumefantrine and halofantrine in rats.

Artemether, artemether-lumefantrine, or coartem and halofantrine are alternative antimalarial drugs to chloroquine. Their efficacy and potential to delay drug resistance in falciparum malaria had led to their increased use. Although these drugs have proven to be well tolerated, there are adverse effects associated with them. This study was designed to examine the toxic potential of acute administration of these drugs in rats. Twenty-four rats were divided into four groups: group I (control) received distilled water; group II received artemether for 5 days with an initial dose of 3.2 g/kg body weight on day 1 and 1.6 mg/kg body weight on days 2-5; group III received coartem (27 mg/kg body weight/day) for 3 days, which was divided into two equal portions per day; and group IV received halofantrine (24 mg/kg body weight/day) in three equal portions. Administration of artemether, coartem and halofantrine caused significant decrease (P < 0.05) in reduced glutathione levels in the liver by 29%, 21% and 26%, respectively. In contrast, there were no significant differences (P > 0.05) in the kidney glutathione levels. Furthermore, artemether, coartem and halofantrine decreased the liver- and kidney-enzymatic antioxidant status of the animals. Precisely, artemether, coartem and halofantrine decreased liver superoxide dismutase and catalase activities by 45%, 50% and 57%; and 20%, 29% and 23%, respectively. While the kidney catalase activities were decreased by 41%, 28% and 30%, respectively, the drugs however did not produce significant effect (P > 0.05) on the kidney superoxide dismutase activities. In addition, artemether, coartem and halofantrine decreased the hepatic levels of glutathione S-transferase by 64%, 51% and 53%, respectively. Administration of artemether, coartem and halofantrine significantly increased (P < 0.05) liver and kidney lipid peroxidation levels by 67%, 50% and 81%; and 58%, 43% and 31%, respectively. This indicates that the liver is considerably more affected than the kidneys. Similarly, halofantrine treatment caused significant elevation (P < 0.05) in the levels of serum creatinine, aspartate and alanine aminotransferases and blood urea nitrogen by 73%, 66%, 61% and 63%, respectively. These data indicate that oral administration of artemether, coartem and halofantrine has adverse effects on both enzymic and non-enzymatic antioxidant status of the animals.

Antiproliferative action of Xylopia aethiopica fruit extract on human cervical cancer cells.

The anticancer potential of Xylopia aethiopica fruit extract (XAFE), and the mechanism of cell death it elicits, was investigated in various cell lines. Treatment with XAFE led to a dose‐dependent growth inhibition in most cell lines, with selective cytotoxicity towards cancer cells and particularly the human cervical cancer cell line C‐33A. In this study, apoptosis was confirmed by nuclear fragmentation and sub‐G0/G1 phase accumulation. The cell cycle was arrested at the G2/M phase with a decreased G0/G1 population. A semi‐quantitative gene expression study revealed dose‐dependent up‐regulation of p53 and p21 genes, and an increase in the Bax/Bcl‐2 ratio. These results indicate that XAFE could be a potential therapeutic agent against cancer since it inhibits cell proliferation, and induces apoptosis and cell cycle arrest in C‐33A cells. Copyright

Dried fruit extract from Xylopia aethiopica (Annonaceae) protects Wistar albino rats from adverse effects of whole body radiation.

The effect of dried fruit extract from Xylopia aethiopica (Annonaceae) (XA) and vitamin C (VC) against γ-radiation-induced liver and kidney damage was studied in male Wistar rats. XA and VC were given orally at a dose of 250 mg/kg, orally for 6 weeks prior to and 8 weeks after radiation (5 Gy). The rats were sacrificed after 1 and 8 weeks of single exposure to radiation. Results showed that all animals in un-irradiated group survived (100%), while 83.3% and 66.7% survived in XA- and VC-treated groups, respectively, and 50% survived in irradiated group. The levels of serum, liver and kidney lipid peroxidation (LPO) were elevated by 88%, 102% and 73% after 1 week of exposure, and by 152%, 221% and 178%, after 8 weeks of exposure, respectively. Treatment with XA and VC significantly (p<0.05) decreased the levels of LPO in the irradiated animals. Also, γ-radiation caused significant decreases (p<0.05) in the levels of liver glutathione (GSH), glutathione-S-transferase (GST), catalase (CAT), superoxide dismutase (SOD), kidney GSH and SOD by 41%, 60%, 81%, 79%, 72% and 58% after 1 week of exposure. Similarly, γ-radiation caused significant increases (p<0.05) in the levels of serum alanine (ALT) and aspartate aminotransferases (AST) after 8 weeks of exposure. Precisely, ALT and AST levels were increased by 69% and 82%, respectively. These changes were significantly (p<0.05) attenuated in irradiated animals treated with XA and VC. These results suggest that XA and VC could increase the antioxidant defence systems in the liver and kidney of irradiated animals, and may protect from adverse effects of whole body radiation.

Methanolic extract of Cnidoscolus aconitifolius attenuates renal dysfunction induced by chronic ethanol administration in Wistar rats.

AIMS The present work studied the modulatory role of methanolic extract of Cnidoscolus aconitifolius leaf (MECA) in rat model of renal dysfunction induced by chronic ethanol administration. METHODS Forty-two male Wistar albino rats weighing between 170 and 180 g were distributed into seven groups of six animals each. Some groups were pretreated with MECA (100 and 200 mg/kg) or kolaviron (KV) (200 mg/kg) for 2 weeks before simultaneous administration of MECA or KV and 20% ethanol (7.9 g/kg) for eight consecutive weeks. Others were given ethanol or MECA (200 mg/kg) or KV alone, and the control received corn oil (Vehicle). KV served as the standard antioxidant. RESULTS In ethanol-treated rats, serum urea, creatinine, urinary glucose, gamma-glutamyltransferase and protein increased by 59, 81, 70, 148 and 63%, respectively, while creatinine clearance significantly (P < 0.05) decreased by 79%. MECA significantly (P < 0.05) attenuated the above biochemical indices to near normal. Also, the levels of serum and kidney malondialdehyde (MDA) (Index of lipid peroxidation) increased by 102 and 143%, respectively, in ethanol-treated rats. Ethanol intoxication caused a significant (P < 0.05) decrease in the levels of catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH) in kidney of the rats. MECA attenuated the ethanol-induced increases in serum and kidney MDA, and also enhanced the antioxidant status of the rats by increasing the levels of CAT, SOD and GSH. The activity of MECA was comparable with KV at 200 mg/kg. The biochemical findings were corroborated by histopathological examination of the kidney. CONCLUSION The results suggest that the renal protective effect of C. aconitifolius leaf extract is by attenuating oxidative stress induced by chronic ethanol administration.

In vitro studies to assess the antioxidative, radical scavenging and arginase inhibitory potentials of extracts from Artocarpus altilis, Ficus exasperate and Kigelia africana

OBJECTIVE To justify the use of Artocarpus altilis (A. altilis), Ficus exasperata (F. exasperata) and Kigelia africana (K. africana) in ethnomedicine for the treatment of several ailments and to evaluate the in vitro antioxidant, radical scavenging and arginase inhibitory potentials of these herbs and compared with catechin (Standard). METHODS Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide, hydrogen peroxide (H2O2) and hydroxyl (OH) radicals scavenging methods. The flavonoids and phenolics content, inhibition of arginase activity, Fe(2+)/ascorbate-induced lipid peroxidation (LPO) and reducing power were also determined. RESULTS The A. altilis, F. exasperata and K. africana showed dose-dependent and significant scavenging of DPPH, H2O2 and OH radicals in vitro relative to catechin. The A. altilis and F. exasperata effectively scavenged DPPH radical with IC50 of 593 and 635 µg/mL and, OH radical with IC50 of 487 and 514 µg/mL, respectively. The DPPH and OH radicals scavenging activities followed the order A. altilis>F. exasperata>K. africana. In addition, A. altilis and F. exasperata significantly (P<0.05) inhibited LPO in a dose-dependent manner. The A. altilis extract had the most potent inhibitory activity against LPO with 79% relative to catechin (28%) at 750 µg/mL. The reducing power followed the order: A. altilis>Catechin>F. exasperata>K. africana at 1 000 µg/mL. The A. altilis at 500 and 750 µg/mL significantly (P<0.05) inhibited arginase activity by 63% and 67%, respectively. The flavonoids contents were found to be highest in A. altilis. CONCLUSIONS Extracts of A. altilis and F. exasperata are potent antioxidative agents with strong radical scavenging activity and inhibition of lipid peroxidation.

Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats

We investigated the toxic effect of nevirapine (NVP; Viramune®), an antiretroviral drug, on the liver, kidney and testis of Wistar rats. Twenty-one rats were assigned into 3 groups of 7 animals each. The first group served as control, and the second and third groups received NVP at 18 and 36 mg/kg body weight, respectively. Clinical signs of toxicity were not observed in the animals. NVP at both doses did not significantly (p > 0.05) alter the body weight gain, relative weights of kidney and testis, serum protein, urea, creatinine and alkaline phosphatase levels of the animals. However, NVP2 significantly (p < 0.05) increased the relative weight of liver, level of serum total bilirubin and activities of γ-glutamyl transferase, alanine and aspartate aminotransferases. NVP administration caused a dose-dependent, significant (p < 0.05) elevation of lipid peroxidation measured as malondialdehyde (MDA) content in the liver, kidney and testis of the rats. Hepatic, renal and testicular MDA were increased by 107%, 80% and 163%, respectively, in NVP2-treated rats. Elevation in MDA was accompanied by a significant (p < 0.05) decrease in the activities of hepatic, renal and testicular superoxide dismutase and catalase. NVP2 caused 43% and 32% decrease in spermatozoa motility and live/dead sperm count, respectively, and 94% increase in total sperm abnormalities. Histopathological findings showed that NVP2 caused degeneration of seminiferous tubules in testis, and severe necrosis in liver slides. NVP induced oxidative stress with corresponding decrease in antioxidant status of the rats. The changes in sperm parameters and, elevation of liver marker enzymes suggest an interference of NVP2 with these organs.

Possible ameliorative effects of kolaviron against reproductive toxicity in sub-lethally whole body gamma-irradiated rats.

Ionizing radiation is one of the environmental factors that may contribute to reproductive dysfunction by a mechanism involving oxidative stress. We investigated the possible ameliorative effects of kolaviron (KV) (a biflavonoid from the seeds of Garcinia kola) on sperm characteristics, testicular lipid peroxidation (LPO) and antioxidant status after a whole body γ-irradiation in Wistar rats. Vitamin C (VC) served as standard antioxidant in this study. The study consists of four groups of 6 rats each. Group I received corn oil, whereas group II received a single dose of γ-radiation (5 Gy). The animals in groups III and IV were pretreated with KV (250 mg/kg) and VC (250 mg/kg) by oral gavage five times in a week, respectively, for 6 weeks prior to and 8 weeks after exposure to γ-radiation. Gamma-irradiation resulted in a significant (p<0.05) decrease in body weight and relative testes weight. Also, γ-irradiation significantly (p<0.05) decreased the activities of superoxide dismutase, catalase and glutathione S-transferase as well as glutathione level, but markedly elevated malondialdehyde levels in the serum and testes. Irradiated rats showed testicular degeneration with concomitant decrease in sperm motility and viability. Although sperm abnormalities significantly increased, it has no effect on the epididymal sperm count. KV and VC significantly (p<0.05) decreased the body weight loss and increased relative testes weights of the rats. Furthermore, supplementation of KV and VC ameliorated radiation-induced toxicity by increasing the activities of antioxidant enzymes, decreased LPO and abrogated testicular degeneration. Taken together, γ-irradiation caused reproductive dysfunction by depleting the antioxidant defence system in the rats, while administration of KV or VC ameliorated the radiation-induced testicular toxicity.

Extract of Xylopia aethiopica (Annonaceae) Protects Against Gamma-Radiation-Induced Testicular Damage in Wistar Rats

Ionizing radiation is an important environmental risk factor and, a major therapeutic agent for cancer treatment. This study was designed to evaluate the protective effect of extract of Xylopia aethiopica (XA) on gamma-radiation-induced testicular damage in rats. Vitamin C (VC) served as the reference antioxidant during the study. The study consists of 4 groups of 11 rats each. Group I received corn oil (vehicle), groups II and IV were pretreated with XA (250 mg/kg) and VC (250mg/kg) for 6 weeks before and 8 weeks after exposure to gamma-radiation; group III was exposed to a single dose of gamma-radiation (5 Gy). Biochemical analysis revealed that gamma-irradiation caused a significant increase (p < .05) in serum and testicular lipid peroxidation (LPO) levels by 217% and 221%, respectively. Irradiated rats had markedly decreased testicular catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and reduced glutathione (GSH) levels. Irradiation resulted in 59% and 40% decreases in spermatozoa motility and live/dead sperm count, respectively, and a 161% increase in total sperm abnormalities. Histologically, testes of the irradiated rats showed extensive degenerative changes in the seminiferous tubules and defoliation of spermatocytes. Supplementation of XA and VC reversed the adverse effects of gamma-radiation on biochemical and histological indices of the rats. These findings demonstrated that Xylopia aethiopica has a protective effect by inhibiting oxidative damage in testes of irradiated rats.

Kolaviron, a biflavonoid fraction from Garcinia kola, protects against isoproterenol-induced injury by mitigating cardiac dysfunction and oxidative stress in rats

Abstract Background: The aim of this study was to evaluate the cardioprotective effects of kolaviron (KV), a biflavonoid from Garcinia kola seeds, in rats intoxicated with isoproterenol chloride (ISO) while quercetin (QUE) served as standard. Methods: Forty-two male Wistar rats (180–200 g) were randomly divided into seven groups of six rats each. Group 1 served as control; group 2 received ISO (85 mg/kg subcutaneously); groups 3, 4 and 5 received ISO and KV1 [100 mg/kg orally (p.o.)], KV2 (200 mg/kg, p.o.) and QUE (25 mg/kg, p.o.), respectively; and groups 6 and 7 received QUE and KV2, respectively. Results: Administration of ISO caused significant (p<0.05) elevation of serum creatine phosphokinase, lactate dehydrogenase, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase by 2.2-, 1.9-, 2.1-, 1.9- and 1.7-fold, respectively, relative to controls, with a concomitant decrease in cardiac activities of these enzymes. Administration of ISO led to significant decrease (p<0.05) in the levels of cardiac superoxide dismutase, catalase, glutathione S-transferase, reduced glutathione and increase in malondialdehyde (MDA). Also, ISO-treated rats had significantly higher values of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol relative to controls. Supplementation with KV2 and QUE caused significant elevation of cardiac antioxidant enzymes, normalized the marker enzymes and reduced MDA levels. Conclusions: KV protects against ISO-induced cardiotoxicity in vivo, suggesting its usefulness as a possible chemoprophylactic agent against cardiotoxic drugs.