Research Of Effects Of Dietary Fatty Acids On Acute Kidney Injury And Related Mechanisms

Rhabdomyolysis induced acute kidney injury(Rha-AKI)is a pathological process caused by the breakdown of muscle tissue,and products from the damaged muscle,including myoglobin,enter kidney through circulatory system and cause damage.Myoglobin plays a crucial role in Rha-AKI.While folic acid induced acute kidney injury(FA-AKI)is associated with acute accumulation of folate crystals in the renal tubules and subsequent acute tubular necrosis.Ferroptosis is a new way of cell death and manifested by iron dependence and lipid peroxidation.It has been reported that ferroptosis might be involved in Rha-AKI and it was proved that ferroptosis was the way of cell death in FA-AKI.Recently,the significant meaning of lipid to renal tissue was found.Renal cells rely on the fatty acid oxidation as their energy source.But no research was performed to explore the effects of dietary fatty acids on these two type of acute kidney injury(AKI).Therefore,investigating the impacts of fatty acids on AKI and the role of ferroptosis in it has important meaning for people who want to intake additional fatty acid in disease state.Renal injuries were caused by intramuscular injection of hypertonic glycerol in Rha-AKI and intraperitoneal injection of folic acid in FA-AKI.Fish oil,camellia seed oil and lard were added to the mice feed as dietary supplement for docosahexaenoic acid(DHA),oleic acid(OA)and saturated fatty acid(SFA).The effects of dietary supplement of fatty acids on two kinds of AKI were analyzed from the damage of renal function,renal histological change and change of blood lipid level.And for the mechanism,oxidative damage,inflammatory response and cell death were explored.An in vitro model was established with a HK-2 cell line.Myoglobin and ferroptosis inducers RSL-3 and Erastin were applied to investigate possible mechanisms by MTT assay,and anion probe DHE was used to reflect the accumulation of intracellular reactive oxygen species(ROS).The main results were as followed:(1)Among the three fatty acids,only dietary supplement of DHA had significant effect on damage in mice with Rha-AKI,which could reduce the extent of renal function insufficiency and tissue damage,as well as reduce subsequent hyperlipidemia.The possible reason was that DHA could alleviate oxidative damage and inflammatory conditions during the process of disease,which may be linked with the increase of cellular DHA and decrease of arachidonic acid(AA),as well as activation of related signal pathways.However,DHA had no effect on the toxicity of myoglobin,the main factor causing disease.(2)Among the three fatty acids,dietary supplement of DHA and OA significantly aggravated renal injury in mice with FA-AKI.The mechanism of DHA's effect was discussed here.The possible reason was that DHA could aggravate ferroptosis and ferroptosis was accompanied by lipid peroxidation so that DHA promoted cell death and tissue oxidative damage.At the same time,ferroptosis was followed by inflammation.Although DHA has anti-inflammation activity,it could not reduce inflammation effectively.Therefore,DHA played a role of aggravate the damage in mice with FA-AKI.In summary,the research proved in mice model that DHA protected kidney damage in Rha-AKI,but promoted the damage in FA-AKI.The main reason was that DHA played an anti-inflammatory role mainly in Rha-AKI whereas in FA-AKI,the effect of aggravating cell death predominated.The research provided a new view for people have daily supplement of fatty acid under disease condition and also give some suggestions for the prevention and treatment of AKI.