Wild black rats (Rattus rattus Linnaeus, 1758) as zoomonitor of genotoxicity and systemic toxicity induced by hazardous emissions from Abule Egba unsanitary landfill, Lagos, Nigeria.

Wild black rats (Rattus rattus) inhabiting Abule Egba landfill (AEL) were used as zoomonitor to assess health risk associated with exposure to hazardous chemicals from landfills. Twenty five R. rattus (16♂ and 9♀) captured within AEL and 15 (9♂ and 6♀) (control) caught from Iyano Ipaja (10 km away from AEL) were examined for bone marrow micronucleated polychromatic erythrocytes (MNPCE) and polychromatic erythrocytes/normochromatic erythrocytes (PCE/NCE) ratio, abnormal sperm morphology, alterations in hematological indices and erythrocyte morphology, and histopathology of the viscera using standard protocols. There was significant (p < 0.05) increase in MNPCE but decrease PCE/NCE ratio in bone marrow cells of exposed rats than the reference site. MNPCE was insignificantly higher in male than females. Cauda epididymal sperms from exposed rats showed significant high frequency of teratozoospermia. Erythrocyte count, hemoglobin concentrations, percentage hematocrits, mean corpuscular hemoglobin concentrations, leucocyte count, and lymphocytes decreased while mean corpuscular volume, neutrophils, and mean corpuscular hemoglobin increased in the exposed rats compared to the control. Also, abnormal erythrocyte morphology: acanthocytes, codocytes (target cells), schizocytes, and tear drops significantly increased in the exposed rats. Marginal sexual dimorphism was observed between males and females in the incidence of hematological indices. Histopathological lesions including interstitial edema, hemorrhage, lymphoid depletion, cellular infiltrations, proliferation of the alveolar pneumocytes, necrosis, tissue degeneration, and reduced germinal epithelium were observed in the testes, liver, lungs, heart, kidney, and spleen from the exposed rats compared to the control. Some physicochemicals and metals analyzed in leachates from the landfill are capable of inducing genome instability and systemic toxicity in the exposed rats. Rattus rattus exposed to hazardous chemicals from AEL harbored somatic and germ cell mutations, and tissue damage compared to the control rats. We suggest that R. rattus are useful sentinel for genotoxicity and system toxicity assessment of landfill-polluted sites.Graphical abstract.

Foetal loss and enhanced fertility observed in mice treated with Zidovudine or Nevirapine.

BACKGROUND: Health concerns for HIV-infected persons on antiretroviral therapy (ART) have moved from morbidity to the challenges of long-term ART. We investigated the effect of Zidovudine or Nevirapine on reproductive capacity across two mouse generations. METHODS: A prospective mouse study with drugs administered through one spermatogenic cycle. Mouse groups (16 males and 10 females) were given Zidovudine or Nevirapine for 56 days. Males were mated to untreated virgin females to determine dominant lethal effects. Twenty females (10 treated and 10 untreated) mated with the treated males per dose and gave birth to the F1 generation. Parental mice were withdrawn from drugs for one spermatogenic cycle and mated to the same dams to ascertain if effects are reversible. The F1 generation were exposed for another 56 days and mated to produce the F2 generation. RESULTS: Foetal loss was indicated in the dominant lethal assay as early as four weeks into drug administration to the males. At the first mating of the parental generation to produce the F1 generation, births from 10 dams/dose when the 'father-only' was exposed to Zidovudine (10, 100 and 250 mg/kg) was 3, 2 and 1 while it was 7, 1 and 4 respectively when 'both-parents' were exposed. Similarly births from the parental generation first mating when the 'father-only' was exposed to Nevirapine (5, 50 and 150 mg/kg) was 2, 2 and 0 while it was 6, 5 and 9 respectively when 'both-parents' were exposed. However, fertility was not significantly different neither by dose nor by the parental exposure. The F1 mice mated to produce the F2 generation recorded only one birth. CONCLUSION: The dominant lethal analysis showed foetal loss occurred when the "fathers-only" were treated while fertility was enhanced when "both-parents" were on therapy at the time of mating.

Exposure of Allium cepa root cells to zidovudine or nevirapine induces cytogenotoxic changes.

Antiretroviral drugs have proved useful in the clinical management of HIV-infected persons, though there are concerns about the effects of exposure to these DNA-reactive drugs. We investigated the potential of the plant model Allium cepa root tip assay to demonstrate the cytogenotoxicity of zidovudine and nevirapine and as a replace-reduce-refine programme amenable to resource-poor research settings. Cells mitotic index were determined in squashed root cells from Allium cepa bulbs exposed to zidovudine or nevirapine for 48 hr. The concentration of zidovudine and nevirapine inhibiting 50% root growth after 96 hr exposure was 65.0 µM and 92.5 µM respectively. Root length of all antiretroviral-exposed roots after 96 hr exposure was significantly shorter than the unexposed roots while additional root growth during a subsequent 48 hr recovery period in the absence of drug was not significantly different. By ANOVA, there was a significant association between percentage of cells in mitosis and zidovudine dose (p=0.004), but not nevirapine dose (p=0.68). Chromosomal aberrations such as sticky chromosomes, chromatin bridges, multipolar mitoses and binucleated cells were observed in root cells exposed to zidovudine and nevirapine for 48 hr. The most notable chromosomal aberration was drug-related increases in sticky chromosomes. Overall, the study showed inhibition in root length growth, changes in the mitotic index, and the induction of chromosomal aberrations in Allium bulbs treated for 96 hr or 48 hr with zidovudine and nevirapine. The study reveals generalized cytogenotoxic damage induced by exposure to zidovudine and nevirapine, and further show that the two compounds differ in their effects on mitosis and the types of chromosomal aberrations induced.