Subacute toxicity of combined drugs for prevention of mother to child transmission of HIV
GE Xian-min, WEN Ping-jing, HUANG Chao-pei, WANG Yan-wu, QIN Hui-yan, LI Bin, YANG Hui, LUO Hai-lan, GAO Yu-qiu, LAN Guang-hua, CHEN Huan-huan, MENG Qin, LUO Liu-hong, LI Shan-shan, LIU Shuai-feng, WU Xiu-ling
Guangxi Zhuang Autonomous Region Center for Disease Prevention and Control, Nanning, Guangxi 530028, China
Abstract:Objective To study the subacute toxic effects of prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) combined drugs of zidovudine (AZT) + lamivudine (3TC) + lopinavir/ritonavir (LPV/r) on rats. Methods Seventy two adult SD rats were randomly divided into the high, medium and low dose groups and the control group, with 18 rats in each group (9 males and 9 females). The rats were given drugs by gavage with the concentrations of 2.00, 0.65 and 0.22 g/kg (based on active ingredients) and pure water, once a day for 28 days, respectively. The rats' general condition, behavior and weight changes were observed. At the end of the experiment, blood routine, biochemical indexes andlymphocyte apoptosis rate were detected, and the main organs were examined by histopathology. Results After administration of the combined drugs, the total weight gain of male rats in the high, medium and low dose groups and female rats in the high dose group was less than that of the control group (P<0.01). Compared with the control group, the liver/body weight of male and female rats in the three combined drug groups increased (P<0.01 or 0.05). The ratios of kidney/body weight, spleen/body weight and brain/body weight of male and female rats in the high dose group were all higher than those in the control group (P<0.01), while the ratio of thymus/body weight of female rats in the high and medium dose groups decreased (P<0.05). HGB of male and female rats in the high and medium dose groups and RBC of male rats in the high and medium dose groups were all lower than those in the control group (P<0.01 or 0.05). WBC of male and female rats in the high and medium dose groups was higher than that in the control group (P<0.01 or 0.05). The apoptosis rate of peripheral blood lymphocytes in male rats of the three dose groups was higher than that in the control group (P<0.01 or 0.05). Compared with the control group, these indicators increased, including ALP of male and female rats in the three dose groups, ALT and LDH of male and female rats in the high dose group, GGTP of male rats in the high and medium dose groups and Glu of male rats in the high dose group (P<0.01 or 0.05). Serum TP and Alb in the three dose groups were lower than those in the control group (P<0.01). BUN of male and female rats in the high dose group and Cr of male rats in the high and low dose groups were higher than those in the control group (P<0.05). Serum Ca of rats in three dose groups decreased (P<0.01 or 0.05). Pathological examination showed that some rats in the combined drug group had follicular hyperplasia and decreased glia in the thyroid gland as well as increased red blood cells and decreased lymphocytes in the splenic sinuses of spleen. Conclusion Under the experimental conditions, AZT+3TC+LPV/r combination drug has potential subacute toxicity to rats.
葛宪民, 温平镜, 黄超培, 王彦武, 覃辉艳, 李彬, 杨慧, 罗海兰, 高玉秋, 蓝光华, 陈欢欢, 孟琴, 罗柳红, 李珊珊, 刘帅凤, 吴秀玲. HIV 阻断母婴传播联合用药的亚急性毒性作用研究[J]. 实用预防医学, 2023, 30(4): 411-415.
GE Xian-min, WEN Ping-jing, HUANG Chao-pei, WANG Yan-wu, QIN Hui-yan, LI Bin, YANG Hui, LUO Hai-lan, GAO Yu-qiu, LAN Guang-hua, CHEN Huan-huan, MENG Qin, LUO Liu-hong, LI Shan-shan, LIU Shuai-feng, WU Xiu-ling. Subacute toxicity of combined drugs for prevention of mother to child transmission of HIV. , 2023, 30(4): 411-415.