Azu Onyemaechi Okpara, Jegede Ayoola Isaac, Ugochukwu Offor, Onanuga Ismail Olasile, Kharwa Salem, Naidu Edwin Coleridge
Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences. Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban 4001, South Africa.
Anatomy Department, Faculty of Basic Medical Sciences, College of Health Sciences, Ladoke Akintola University of Technology, Ogbomoso, Osun, Nigeria.
Toxicol Rep. 2016 Jan 6;3:114-122. doi: 10.1016/j.toxrep.2015.12.013. eCollection 2016.
As the roll-out of antiretroviral therapy continues to drive downwards morbidity and mortality in people living with HIV/AIDS (PLWHAs), organ toxicities (especially the liver) are frequently becoming a major concern for researchers, scientists and healthcare planners. This study was conducted to investigate the possible protective effect of (AP) against highly active antiretroviral therapy (HAART)-induced hepatotoxicity. A total of 63 pathogen-free adult male Sprague-Dawley rats were divided into 9 groups and treated according to protocols. While no mortality was reported, animals treated with adjuvant HAART and AP recorded least% body weight gain. Significant derangements in serum lipid profiles were exacerbated by treatment of with AP as LDL (increased < 0.03), triglycerides (increased < 0.03) with no change in total cholesterol levels. Adjuvant AP with HAART caused reduction in LDL ( < 0.05 and 0.03), increased HDL ( < 0.05) and TG ( < 0.05 and 0.001 for AP and AP doses respectively). Markers of liver injury assayed showed significant increase ( < 0.003, 0.001) in AST in AP alone as well as HAART+ vitamins C and E groups respectively. Adjuvant HAART and AP and vitamins C and E also caused significant declines in ALT and ALP levels. Serum GGT was not markedly altered. Disturbances in histopathology ranged from severe hepatocellular distortions, necrosis and massive fibrosis following co-treatment of HAART with vitamins C and E as well as HAART alone. These results warrant caution on the adjuvant use of AP with HAART by PLWHAs as implications for hepatocellular injuries are suspect with untoward cardiometabolic changes.
随着抗逆转录病毒疗法的推广持续降低艾滋病毒/艾滋病患者（PLWHAs）的发病率和死亡率，器官毒性（尤其是肝脏毒性）日益成为研究人员、科学家和医疗规划者的主要关注点。本研究旨在调查[具体物质]（AP）对高效抗逆转录病毒疗法（HAART）诱导的肝毒性的可能保护作用。总共63只无病原体的成年雄性Sprague-Dawley大鼠被分为9组，并根据方案进行治疗。虽然未报告有死亡情况，但接受辅助HAART和AP治疗的动物体重增加百分比最低。AP治疗加剧了血清脂质谱的显著紊乱，低密度脂蛋白（LDL）升高（<0.03），甘油三酯升高（<0.03），而总胆固醇水平无变化。HAART联合AP导致LDL降低（<0.05和0.03），高密度脂蛋白（HDL）升高（<0.05）以及甘油三酯降低（AP和不同剂量AP分别为<0.05和<0.001）。检测的肝损伤标志物显示，单独使用AP以及HAART + 维生素C和E组的天冬氨酸转氨酶（AST）均显著升高（<0.003，<0.001）。辅助HAART、AP以及维生素C和E也导致谷丙转氨酶（ALT）和碱性磷酸酶（ALP）水平显著下降。血清γ-谷氨酰转移酶（GGT）无明显改变。组织病理学紊乱范围从HAART与维生素C和E联合治疗以及单独使用HAART后的严重肝细胞变形、坏死和大量纤维化。这些结果警示PLWHAs在HAART中辅助使用AP时要谨慎，因为可能会对肝细胞造成损伤，并伴有不良的心脏代谢变化。
