Comparison of antioxidant effects of kolaviron and vitamin C interventions on testicular structures following nevirapine administration in Sprague-Dawley rats / Comparación de los efectos antioxidantes en la intervención con kolaviron y vitamina C sobre las estructuras testiculares después de la administración de nevirapina en ratas Sprague-Dawley

Testicular toxicity has been implicated in highly active anti-retroviral therapy (HAART) treatment. Hence there is need to identify an effective antioxidant product that can alleviate testicular necrosis due to HAART administration. Forty eight adult male Sprague-Dawley rats were used in this study. The animals were divided into eight (8) groups: A-H (n= 6). Group A animals received normal saline as the control; Group B was given Nevirapine (Nv); Group C was given Kolaviron (Kv); Group D was given vitamin C; Group E was given Nv and Kv; Group F was given Nv and Vitamin C; Group G was given Nv for 56 d and Kv for 28 d serving as a withdrawal group; Group H was given corn oil. Nv, Kv and Vit. C were given at 1.54, 200 and 250 (mg·kg)/bw respectively while all administrations were through oral gavage. The body weights were taken every other day. Thereafter, they were anaesthetized with halothane. The testes were excised, weighed, fixed in Bouin's fluid and stained with H&E while the epididymes removed for semen fluid analyses. The results showed a significant (P<0.05) decrease in sperm motility in group E (Nevirapine + kolaviron) when compared with group F (Nevirapine + Vitamin C) while Sperm count was not significantly different (P>0.05) across the groups. The testicular histoarchitectural studies revealed indistinct spermatogonia, necrotic interstititial endocrine cells in the altered interstitial space, fragmented spermatids, atrophy of mature spermatocytes, degenerated germ cells, obliterated seminiferous tubules lumen, undifferentiated spermatogonia and cellular debris in the somniferous tubules lumen of nevirapine administered group but normal across the other groups. In the testis, there were no significant reduction in SOD, Catalase and GPx activities but a significant decrease in GST activity (P<0.001) when group E was compared with group F. In conclusion, vitamin C presents a better remediation in nevirapine induced spermiotoxicity compared to kolaviron in Sprague-Dawley rats.

La toxicidad testicular ha sido implicada en la terapia antirretroviral altamente activa (TARAA). Por lo tanto existe la necesidad de identificar un producto antioxidante eficaz que pueda aliviar la necrosis testicular en la administración de la TARAA. Cuarenta y ocho ratas macho Sprague-Dawley adultas fueron utilizadas. Los animales se dividieron en ocho (8) grupos: AH (n= 6). Grupo A, animales recibieron solución salina normal como el control; Grupo B, recibió Nevirapina (Nv); Grupo C, recibió Kolaviron (Kv); Grupo D, recibió vitamina C; Grupo E, recibió Nv y Kv; Grupo F, recibió Nv y vitamina C; Grupo G, recibió Nv durante 56 d y Kv por 28 d como un grupo de retirada; Grupo H, recibió aceite de maíz. Nv, Kv y Vit. C se administraron en dosis de 1, 54, 200 y 250 (mg · kg) de peso corporal respectivamente; todas las administraciones fueron por sonda oral. Los pesos corporales se tomaron cada dos días. A partir de ese momento los animales fueron anestesiados con halotano. Los testículos fueron extirpados, pesados y fijados en solución de Bouin y teñidos con H&E, mientras que el epidídimo se retiró para analizar el semen. Los resultados mostraron un descenso (p<0,05) en la motilidad de los espermatozoides en el grupo E (Nevirapina + Kolaviron) en comparación con el grupo F (Nevirapina + vitamina C), mientras que el recuento espermático no mostró diferencias significativas (P>0,05) entre los grupos. El estudio de la histoarquitectura testicular reveló espermatogonias indiferenciadas, con células intersticiales necróticas en el espacio intersticial y espermátidas fragmentadas. Además, en el grupo que recibió Nevirapina mostró espermatocitos maduros atrofiados, degeneración de células germinales, lumen de los túbulos seminíferos obliterados, espermatogonias indiferenciadas y restos celulares en el lumen de los tubulos seminíferos. En el resto de los grupos los resultados fueron normales. En el testículo hubo una reducción significativa en las actividades de la superóxido dismutasa, catalasa y glutatión peroxidasa, pero una disminución significativa en la actividad glutatión S-transferasa (P <0,001) al comparar los grupo E y F.

Comparative study on the efficacy of Garcinia kola in reducing some heavy metal accumulation in liver of Wistar rats.

Garcinia kola is regarded as an antidote and anti-hepatotoxic agent. We examined its protection ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. The ground seed was mixed with rat feed (5%, w/w) and fed to rats while Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) was given in drinking water. Garcinia kola was administered either at the same time with the metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. The heavy metal accumulations in the liver were determined using AAS. Garcinia kola could not reverse the weight reduction in the heavy metal exposed groups although it offers more protection and aid greater elimination of heavy metals from the liver. There was a significant (P<0.01) increase in protection by Garcinia kola to Cd (72.4%) and Pb (56.2%) accumulation when compared to Hg (40%) at week 2 which was significantly (P<0.01) decreased at week 4 when compared to week 2. At week 6, the percentage protection to both Hg (64.2%) and Cd (62.2%) were comparable to each other while protection to Pb (49.9%) accumulation was significantly (P<0.01) reduced. The percentage protection was time-dependent in some groups but treatment during and after the exposure provided a greater protection. Garcinia kola has the highest hepatoprotective effect to Cd followed by Hg and least protection against Pb toxicity in rats and its administration is beneficial in reducing heavy metal accumulation in the liver.

Endothelium-independent vasodilation induced by kolaviron, a biflavonoid complex from Garcinia kola seeds, in rat superior mesenteric arteries.

Previous studies have established the hepatoprotective, gastroprotective, hypolipidemic and hypoglycemic effects of kolaviron (KV), a biflavonoid complex from Garcinia kola seeds. In this study, we investigated the mechanisms involved in the vasorelaxant effects of KV in isolated superior mesenteric arteries from normotensive rats. KV (1, 10, 30, 100, 300, 500 and 1,000 microg/ml) concentration-dependently inhibited the contractions induced by phenylephrine (PHE) (10 microM) and KCl (80 mM) in both endothelium-intact (E(max) = 58.3 +/- 1.7% and 51.4 +/- 1.3%, respectively) and -denuded rings (E(max) = 59.3 +/- 5.5% and 64.3 +/- 2.4%, respectively). Furthermore, KV reduced CaCl(2)-induced contraction in Ca(2+)-free medium containing KCl 60 mM, thus acting as a Ca(2+)-antagonist. In addition, KV inhibited the transient contraction by PHE in Ca(2+)-free medium containing EGTA, suggesting a possible action on the release of intracellular Ca(2+) via the inositol-1,4,5-triphosphate (IP(3)) pathway. KV is not a specific alpha-adrenoceptor blocker, since it also caused a concentration-dependent inhibition of contractile responses to KCl, suggesting that KV also blocks the L-type Ca(2+)-channel. As a Ca(2+) antagonist, KV (100 microg/ml) potentiates the relaxant effects of nifedipine in denuded rings (E(max) = 97.6 +/- 1.2%; control = 75.1 +/- 3.0%, P<0.05). Also, the vasorelaxation induced by KV was significantly inhibited after pre-treatment of the denuded rings with 4-aminopyridine (4-AP) 1 mM, a selective blocker of voltage-dependent K(+) (K(v)) channels and, tetraethylammonium (TEA) 1 mM or charybdotoxin (ChTX) 0.1 microM, non-selective blockers of large and intermediate conductance Ca(2+)-activated K(+) (BK(Ca)) channels. In contrast, neither glibenclamide (10 microM), BaCl2 (1 mM) nor apamin (0.1 microM), blockers of K(ATP), K(IR) and SK(Ca) channels, respectively affected the KV-induced vasorelaxation. In conclusion, our results provide functional evidence that the vasorelaxant effects by KV involve extracellular Ca(2+) influx blockade, inhibition of intracellular Ca(2+) release and the opening of K(+) channels sensitive to 4-AP and ChTX with a resultant membrane hyperpolarization/ repolarization.

Histopathological studies on the effects of the ethanolic extract of the fruits of Garcinia kola on selected organs of the dog

The ethanolic extract of Garcinia kola was administered to dogs to investigate the possible effects on selected organs of the dog. Two doses of the extract (500mg/Kg and lOOOmg/Kg) were daily administered to the test animals for a period of 6 weeks. A dose related response was observed in the severity of histopathological changes observed in the testes, liver, kidney and small intestine of animals in the test groups. Despite the reported potentially beneficial effects of Garcinia kola, its use as a medicinal plant should be with great caution.

Fue administrado a perros extracto etanólico de Garcinia kola, para investigar los posibles efectos sobre determinados órganos. Dos dosis del extracto (500mg/Kg y lOOOmg/Kg) fueron administradas diariamente a los animales durante un periodo de 6 semanas. Se observó una relación de la dosis con la gravedad en la respuesta de los cambios histopatológicos observados en testículos, hígado, riñón e intestino delgado de los animales. A pesar de los informes sobre efectos potencialmente beneficiosos de Garcinia kola, su uso como planta medicinal debe ser con mucha precaución.

Biocidal activity of partially purified fractions from methanolic extract of Garcinia kola (Heckel) seeds on bacterial isolates.

The in vitro antibacterial activity of crude methanolic extract of the seeds of Garcinia kola was investigated. The extracts exhibited antibacterial activities with zones of inhibition ranging from 10 mm to 25 mm. The minimum inhibitory concentration of the diethyl ether fraction was between 0.313 and 5.0 mg/ml, while that of butanol fraction varied from 0.157 to 5.0 mg/ml. The butanol fraction killed about 77% of Bacillus anthracis and 79% of Escherichia coli cells within 120 min at a concentration of 5.0 mg/ml. Protein leakage from the B. anthracis and E. coli cells when exposed to the butanol and diethyl ether fractions was observed. We conclude that Garcinia kola seed extract has a broad spectrum antibacterial activity, with the butanol and diethyl ether fractions being bactericidal as exemplified by the killing rate and protein leakage regimes, which suggest cell membrane disruption as a mechanism of action of the extract.

Biocidal activity of partially purified fractions from methanolic extract of Garcinia kola (Heckel) seeds on bacterial isolates

The in vitro antibacterial activity of crude methanolic extract of the seeds of Garcinia kola was investigated. The extracts exhibited antibacterial activities with zones of inhibition ranging from 10 mm to 25 mm. Theminimum inhibitory concentration of the diethyl ether fraction was between 0.313 and 5.0 mg/ml, while that of butanol fraction varied from 0.157 to 5.0 mg/ml. The butanol fraction killed about 77% of Bacillus anthracis and 79% of Escherichia coli cells within 120 min at a concentration of 5.0 mg/ml. Protein leakage from the B. anthracis and E. coli cells when exposed to the butanol and diethyl ether fractions was observed. We conclude that Garcinia kola seed extract has a broad spectrum antibacterial activity, with the butanol and diethyl ether fractions being bactericidal as exemplified by the killing rate and protein leakage regimes, whichsuggest cell membrane disruption as a mechanism of action of the extract.