Histostereological Teratogenic Effects of Gentamicin on the Fetal Kidneys in Albino Rats (Rattus Norvegicus)

Abstract

The nephroteratogenic effects of gentamicin on developing fetal kidneys when prenatally exposed has been a subject of controversy with some studies showing that gentamicin is teratogenic while others showing it is not. At the same time information on whether or not the teratogenic effects of gentamicin are time and dose dependent is generally lacking. This current study therefore aimed to evaluate the histomophological and steriological effects of gentamicin when prenatally exposed in varying doses and at different window periods. The study was carried out in SAFARI animal house of JKUAT and a static-group controlled-experimental study design was adopted. A total of 30 Albino rats dams weighing between 200-250grams (aged 11/2 months) from a pure colony were used in the study. These 30 dams were randomly assigned in to two broad study groups of 3 rats in control and 27 rats in experimental. To evaluate whether the gentamicin nephro-teratogenecity is dose dependant, the 27 rats in the experimental group were further subdivided into three study groups (of 9 rats each) of Low [LDGG-19g/kg/bwt], medium [MDGG-28g/kg/bw], and High gentamicin dose group [HDGG-37g/kg/bw]. To further evaluate whether gentamicin nephro-teratogenicity is time dependant, the 9 rats in each of the three dose groups of low, medium and high gentamicin were further sub-divided into three sub groups according to the time of exposure as follows, 3 rats for TM1, 3 rats for TM2, and 3 rats for TM3. All rats received standard rodent diet and water adlibitum while those rats in experimental category received gentamicin as per their study groups. All rats were humanly sacrificed at GD20 and then 3 fetuses with the lowest, median and highest weight from each mother selected and their kidneys harvested, weighed and processed for histo-morphological and stereological analysis. Data was collected using structured coded tally sheets, entered and stored in excel and analysed by SPSS version 23.0. One-way Analysis of Variance (ANOVA), followed by Tukey’s post hoc multiple comparison tests were done and results expressed as mean ± standard error of the mean (SEM) for all values. All results whose comparatives P - value was less than 0.05 were considered to be statistically significant. This study established that there was no significant reduction in the mean maternal weight gain across doses and trimesters (P>0.05) but there was reduction in all fetal growth parameters in all the gentamicin treated groups especially in 1st and 2nd trimester at LDGG, MDGG and HDGG (P<0.05). Histologically it was clearly demonstrated by the marked increase in thicknesses of all cortical and medullary layers of the fetal kidneys in treatment group especially in 1st and 2nd trimester across all doses. Steriologically when a comparative mean kidney length was done across the three trimesters TM1, TM2 and TM3, it was depicted that at TM1 the mean fetal kidney length was highest in the HDGG group at 0.12±0.0121 followed by MDGG at 0.216±0.008 and LDGG at 0.297±0.0033. This was found to be statistically higher as compared with the control (p<0.05) at 0.395±0.005. This teratogenicity was also observed to be dose dependant with the high gentamicin doses of 37mgs/Kg/Bwt per day being the most critical gentamicin teratogenic dose. The study recommends that gentamicin usage during pregnancy should be eluded unless established that the benefit to the mother outweighs the anticipated teratogenic outcomes to the fetus. Further studies need to be carried in higher primates.