Early assessment of nephrotoxic injury in rats induced by exposure to different heavy metal solid wastes

Abstract

Abstract Numerous countries worldwide face significant challenges in managing Heavy metal solid wastes (HMSWs) and their associated health impacts. Despite the recognized harmful nature of heavy metals, there is a scarcity of data on the specific toxicity of HMSWs. This study utilized comparative toxicogenomic analysis of nephrotoxicity-related gene sets for heavy metals, including Fe, Cu, Co, Ni, and Mn, from the Comparative Toxicogenomics Database (CTD). Moreover, this study conducted animal experiments involving five groups of Sprague Dawley rats that were orally administered substances for a duration of 4 weeks. The control group received 1.1µM acetic acid, whereas the experimental groups were treated with leachates from copper sulfide, copper concentrate, iron ore, and cobalt-nickel-manganese ore. The rats in the treated groups exhibited reduced body weight gain, significantly decreased hematological parameters, increased white blood cell count, decreased superoxide dismutase (SOD) activity in kidney tissues, elevated malondialdehyde (MDA) levels, increased blood lactate dehydrogenase (LDH) activity, increased blood urea nitrogen (BUN), increased creatinine (Cr), and an elevated BUN/Cr ratio. Additionally, the glomerular filtration rate (GFR), BUN, and urine Cr were decreased in the treated groups. Further decision tree analysis revealed that blood LDH levels > 6.82U/gprot distinguished the treatment of cobalt-nickel-manganese and copper sulfide slag from the others, indicating the importance of blood LDH as an oxidative damage marker in assessing nephrotoxicity. Toxicogenomic analysis unveiled that the process of heavy metal- induced kidney damage involves oxidative stress, inflammatory responses, and apoptotic signaling. It also uncovered different programmed cell death processes including ferroptosis and apoptosis, in kidney cells. This study sheds light on the toxic effects of exposure to HMSWs and proposes that LDH, as an oxidative damage marker, could be pivotal in the early assessment of heavy metal-induced nephrotoxicity to safeguard public health.