Here, we investigate the effects of renal ischemia/reperfusion (I/R) on the degree of renal injury, dysfunction, and inflammation in interleukin (IL)-6 knockout (IL-6^-/-) mice and mice administered a monoclonal antibody against IL-6. IL-6^-/- mice were subjected to bilateral renal artery occlusion (30 min) and reperfusion (24 h). At the end of experiments, indicators and markers of renal dysfunction, injury, and inflammation were measured. Kidneys were used for histological evaluation of renal injury. Renal expression of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and P-selectin, as well as nitration of proteins in the kidney, were determined using immunohistochemistry. In addition, wild-type mice were pretreated (24 and 1 h before ischemia) with an IL-6 antibody to mimic the effects that would be seen in IL-6^-/- mice. IL-6^-/- mice and wild-type mice administered the IL-6 antibody demonstrated significantly reduced plasma urea and creatinine levels, indicating reduction of renal dysfunction caused by I/R. Neutrophil infiltration was also significantly reduced in IL-6^-/- mice and wild-type mice administered the IL-6 antibody subjected to renal I/R. Proinflammatory cytokines (tumor necrosis factor-α and IL-1β) in renal tissues were significantly attenuated in IL-6^-/- mice to levels seen in wild-type mice. IL-6^-/- mice demonstrated reduced histological evidence of tubular injury and markedly reduced immunohistochemical evidence of ICAM-1, P-selectin, and nitrotyrosine when subjected to renal I/R. We propose that endogenous IL-6 enhances the degree of renal injury, dysfunction, and inflammation caused by I/R of the kidney by promoting the expression of adhesion molecules and subsequent oxidative and nitrosative stress.

Perfluorinated and polyfluorinated alkyl substances (PFAS), more than 4700 in number, are a group of widely used man-made chemicals that accumulate in living things and the environment over time. They are known as “forever chemicals” because they are extremely persistent in our environment and body. Because PFAS have been widely used for many decades, their presence is evident globally, and their persistence and potential toxicity create concern for animals, humans and environmental health. They can have multiple adverse health effects, such as liver damage, thyroid disease, obesity, fertility problems, and cancer. The most significant source of living exposure to PFAS is dietary intake (food and water), but given massive industrial and domestic use, these substances are now punctually present not only domestically but also in the outdoor environment. For example, livestock and wildlife can be exposed to PFAS through contaminated water, soil, substrate, air, or food. In this review, we have analyzed and exposed the characteristics of PFAS and their various uses and reported data on their presence in the environment, from industrialized to less populated areas. In several areas of the planet, even in areas far from large population centers, the presence of PFAS was confirmed, both in marine and terrestrial animals (organisms). Among the most common PFAS identified are undoubtedly perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA), two of the most widely used and, to date, among the most studied in terms of toxicokinetics and toxicodynamics. The objective of this review is to provide insights into the toxic potential of PFAS, their exposure, and related mechanisms.