Virology

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Effect of tenofovir, an antiretroviral drug, on hepatic and renal functional indices of Wistar rats: protective role of vitamin E
(Walter de Gruyter GmbH (De Gruyter), 2012) Adaramoye, O. A.; Adewumi, M. A.; Adesanoye, O. A.; Faokunla, O. O.; Farombi, E. O.
Tenofovir (TFR) is a nucleotide reverse transcriptase inhibitor with activity against human immunodeficiency virus. We studied the effect of TFR administered to Wistar rats on hepatic and renal function markers and the possible modulatory role of vitamin E (Vit E). The study consists of four groups of six rats each. The fi rst group served as control, the second group received TFR at 50 mg/kg/day for 4 weeks, third group received TFR and Vit E, and the last group received Vit E alone. TFR administration caused a significant (p< 0.05) increase in the levels of serum urea, creatinine, urinary glucose, and protein by 65 % , 51 % , 88 % , and 79 % , respectively, relative to controls. This was followed by a signifi cant (p< 0.05) reduction in creatinine clearance of TFR-treated rats. There were no significant differences (p > 0.05) in the activities of serum aminotransferases,, glutamyl transferase and alkaline phosphatase in TRF-treated rats relative to controls. TFR administration caused a marked elevation of malondial dehyde (MDA; index of lipid peroxidation) in the animals. Specifi cally, serum, hepatic, and renal MDA levels increased by 75 % , 90 % , and 102 % , respectively. TRFtreated rats had signifi cantly (p < 0.05) reduced activities of renal catalase, glutathione- S -transferase, and superoxide dismutase. Supplementation of Vit E ameliorated TFR-induced effects by decreasing the levels of MDA and enhancing the activities of renal antioxidative enzymes. The biochemical data were supported by histopathological fi ndings from the slides.TFR increased oxidative stress and altered kidney function markers in the rats, whereas supplementation of Vit E attenuated these effects.
Lopinavir/ Ritonavir, an Antiretroviral Drug, Lowers Sperm Quality and Induces Testicular Oxidative Damage in Rats
(Tokai University School of Medicine, 2015) Adaramoye, O. A.; Akanni, O. O.; Adewumi, O. M.; Owumi, S .E.
Lopinavir/Ritonavir (KaletraR) is a protease inhibitor used in the management of HIV infection. The increased incidence of toxicity of antiretroviral therapy (ART) has necessitated proper evaluation of their effects on reproductive health. Therefore, this study was designed to investigate the effects of KaletraR on male reproductive system in Wistar rat. Methods: Eighteen rats were assigned into three groups. The first group served as control while the second and third groups received KaletraR at therapeutic dose (8.3 mg/kg) (Kaletra-T) and twice therapeutic dose (16.6 mg/kg) (Kaletra-2T). KaletraR was given orally for 21 days. Administration of KaletraR caused a significant (p = 0.023) decrease in body weight-gain of rats. Precisely, Kaletra-T and Kaletra-2T decreased body weight-gain by 43% and 48%, respectively. Kaletra-T and kaletra-2T significantly (p = 0.016-0.036) decreased sperm motility and sperm count while kaletra-2T increased total sperm abnormalities in the rats. Also, KaletraR (at the two doses) caused a significant (p = 0.02-0.04) increase in the levels of testicular lipid peroxidation with a concomitant decrease in antioxidant indices. Specifically, Kaletra-T and Kaletra-2T decreased the activities of glutathione peroxidase by 38% and 57%, catalase by 40% and 48%, glutathione-s-transferase by 32% and 35% and superoxide dismutase by 47% and 52%, respectively while Kaletra-2T decreased reduced glutathione by 49%. Photomicrographs of testis from control and Kaletra-T groups showed normal seminiferous tubules with abundant spermatogenic cells while Kaletra-2T group had few and abnormal shape spermatogenic cells. KaletraR induces oxidative damage in testis of rats leading to changes in sperm characteristics and antioxidant status of the animals.
Studies on the toxicological effect of nevirapine, an antiretroviral drug, on the liver, kidney and testis of male Wistar rats
(SAGE Publications, 2011-10) Adaramoye, O. A.; Adesanoye, O. A.; Adewumi, O. M.; Akanni, O.
African Journal of Biotechnology Vol. 8 (6), pp. 941-948,We investigated the toxic effect of nevirapine (NVP; Viramune1), 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 g-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.