Hexachlorobutadiene (HCBD) is a potent nephrotoxin which nowadays contaminates human foods and water. On the other hands, it has been reported that rutin is a chemopreventive flavonoid which exerts some protective effects on the kidney. Therefore, in this work, the possible effect of rutin on HCBD-induced nephrotoxicity was investigated in female rats. The animals were divided into five groups. Groups 1 and 2 were treated with vehicle and HCBD (100 mg/kg, i.p.), respectively. Groups 3-5 were pretreated with rutin (100, 500 and 1000 mg/kg, i.p.) 1 h before HCBD injection. The level of serum urea and creatinine as well as urinary glucose and protein were measured. Total thiol content and lipid peroxidation level were also determined in the kidney homogenate. When compared to control group, a significant increase in the level of serum creatinine and urea (p < 0.001) as well as urine glucose and protein (p < 0.001) were observed after 24 h of HCBD administration. HCBD also caused a significant decrease in total thiol content (p < 0.001) and a significant increase in lipid peroxidation level (p < 0.001). Pretreatment with rutin could decrease serum creatinine (p < 0.001) and urea (p < 0.001) as well as urine protein (p < 0.001) concentrations when compared with HCBD treated rats. No significant modification on urine glucose was seen (p > 0.05). Rutin also reversed the HCBD-induced depletion in thiol content (p < 0.001) and elevation in lipid peroxidation (p < 0.001) in the kidney. The results of present study showed that rutin clearly attenuated HCBD-induced nephrotoxicity and has the potential to be considered as a nephroprotective agent.

In this study, we want to understand whether crocin could prevent mitochondrial damage caused by As III. For this purpose, we determined different mitochondrial toxicity endpoints caused by As III. We evaluated mitochondrial ROS formation, lipid peroxidation, mitochondrial membrane potential (MMP) collapse, mitochondrial outer membrane integrity and cytochrome c release. Our results showed that pretreatment with crocin at a concentration of 25 µg/ml significantly (p < 0.001) reduced As III-induced mitochondrial ROS formation, lipid peroxidation, MMP collapse and mitochondrial swelling. Crocin also protected the mitochondria by decreasing the mitochondrial outer membrane damage that leads to reduce the amount of cytochrome c release. These results demonstrated that crocin is a promising antidotal candidate by ameliorating As III-induced oxidative stress through mitochondrial targeting.

Perfluorooctanesulfonate (PFOS), an anthropogenic fluorosurfactant, is one of the most common global pollutants. PFOS is used in various consumer products to provide soil, oil, and water resistance to materials used in clothing, upholstery, and food packaging. PFOS is persistent, bioaccumulative, and toxic to mammalian species. In this study, the cellular mechanisms involved in PFOS hepatotoxicity were evaluated. For this purpose, we determined oxidative stress markers including cell lysis, ROS generation, lipid peroxidation, glutathione depletion, mitochondrial membrane potential decrease, lysosomal membrane leakiness, and cellular proteolysis. Our results demonstrated that PFOS liver cytotoxicity was associated with reactive oxygen species (ROS) formation and lipid peroxidation in isolated rat hepatocytes. Incubation of hepatocytes with PFOS caused rapid depletion of hepatocyte glutathione (GSH), an important marker of cellular oxidative stress. Most of the PFOS-induced GSH depletion could be attributed to the expulsion of glutathione disulfide (GSSG). PFOS hepatotoxicity was inhibited by antioxidants and ROS scavengers, mitochondrial permeability transition (MPT) pore sealing agents, and endocytosis inhibitors. Our results suggest that PFOS hepatotoxicity might be the result of oxidative stress-induced lysosomal membrane leakiness and cellular proteolysis in rat hepatocytes.

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