ABSTRACT
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.
Subject(s)
Animals , Male , Rats , Antioxidants/pharmacology , Garcinia kola/chemistry , Nevirapine/toxicity , Plant Extracts/pharmacology , Superoxide Dismutase/antagonists & inhibitors , Testis/drug effects , Anti-HIV Agents/toxicity , Ascorbic Acid/pharmacology , Biflavonoids/pharmacology , Body Weight , Catalase/antagonists & inhibitors , Glutathione Peroxidase/antagonists & inhibitors , Rats, Sprague-Dawley , Seeds , Sperm Count , Sperm Motility/drug effects , Testis/enzymology , Testis/pathologyABSTRACT
Rats pre-administered with alpha-tocopherol (10 mgs/day) for 7 days afforded a significant protection at the tissue level against the lowering of superoxide dismutase and glutathione peroxidase, especially the selenium-dependent glutathione peroxidase. The protective action of alpha-tocopherol in the diethyldithiocarbamate treated rats may be attributed to its antioxidant/free radical scavenging action. It is concluded that selenium-dependent glutathione peroxidase and alpha-tocopherol act in a complementary fashion to block free radical formation.
Subject(s)
Animals , Antioxidants/pharmacology , Cytoprotection/drug effects , Ditiocarb/toxicity , Free Radicals/analysis , Glutathione Peroxidase/antagonists & inhibitors , Liver/drug effects , Male , Rats , Rats, Wistar , Superoxide Dismutase/antagonists & inhibitors , Time Factors , alpha-Tocopherol/pharmacologyABSTRACT
Intraperitoneal injection of rats with diethyldithiocarbamate (1.2 g/kg body wt) led to maximum diminution of superoxide dismutase activity at 1 hr by 86 and 84% in liver and red blood cell respectively with a gradual return to the normal level at 48 hr after administration of injection. Significant inhibition of selenium-dependent glutathione peroxidase was also observed, which returned to normal at 48 hr after administration of injection. However, maximum decline in its activity was at 12 hr by 52 and 73% in liver and red blood cells respectively. No significant difference in tissue level of selenium-independent glutathione peroxidase was observed during time course study after diethyldithiocarbamate administration. It is possible that inhibition of superoxide dismutase by diethyldithiocarbamate leads to accumulation of superoxide anion which in turn inactivates selenium-dependent glutathione peroxidase by its reaction with selenium at the active site of the enzyme.