Long-term biopermanence of ceramides, cholesteryl esters, and ether-linked triglycerides with very-long-chain PUFA in the cadmium-damaged testis

Abstract

Cadmium is known to harm rat testis by causing the dose-dependent apoptotic or necrotic death of seminiferous epithelium cells. Here we investigated how this affects the lipids with long-chain (C18-C22) and very-long-chain (C24-C32) polyunsaturated fatty acids (VLCPUFA) typical of spermatogenic and Sertoli cells. A severe acute inflammatory reaction resulted from the massive necrotic death of these cells two days after a single high (4 mg/kg) dose of CdCl2. This led to the conversion of most testicular glycerophospholipids to diradylglycerols (DRG) and free fatty acids (FFA) and of most sphingomyelins to ceramides (Cer). By day 30 the testis weight had decreased three fold. The DRG and FFA had been metabolized but, unexpectedly, ceramides persisted. Also slow to disappear were VLCPUFA-containing triacylglycerols from former germ cells and ether-linked triglycerides and cholesteryl esters (CE) from former Sertoli cells. Similar results were observed 30 and 45 days after administering repeated small non pro-inflammatory CdCl2doses (1 mg/kg). At day 30 after both treatments, an amorphous material replaced the original seminiferous tubules and testicular macrophages populated the interstitium. Species of CE and ether-linked triglycerides containing fatty acids other than VLCPUFA steadily accumulated in the irreversibly damaged testis, a manifestation of the activity of phagocytic cells. The long-term permanence of original VLCPUFAcontaining neutral lipids, especially ceramides, indicates that these cells were slow to clear out the acellular material contained in seminiferous tubules, pointing to a form of silent chronic inflammation as an additional outcome of the multifactorial commotion caused in the testis by experimentally administered cadmium. We are submitting the manuscript entitled "Long-term biopermanence of ceramides, cholesteryl esters and ether-linked triglycerides with very-long-chain polyunsaturated fatty acids in the cadmium-damaged testis" by Dr. S. R. Zanetti and myself, to be considered for publication in BBA-Molecular and Cell Biology of Lipids.The lipids of the cells present in the seminiferous tubules of the adult rat testis are so unique that they can be used as biomarkers of biochemical processes that take place under different experimental conditions. For example, in the present study, the massive hydrolysis of germ cell sphingomyelin into ceramide that occurs after the Cd-induced death of germ cells can be recognized because of the unusual very long-chain polyunsaturated fatty acids (e. g., 28:4, 30:5) these two lipids contain. This is also the case of neutral lipids like cholesteryl esters and etherlinked triglycerides, Sertoli cell products that have specific very-long-chain fatty acids (like 28:5 or 24:5, respectively) in addition to the major long-chain PUFA of rat testis lipids, 22:5n-6. The long-term biopermanence of these neutral lipids is remarkable, our results showing that, in contrast to glycerophospholipids, they are slow to be metabolized by the immune cells that popul...

Green olive leaf extract (OLE) provides cytoprotection in renal cells exposed to low doses of cadmium

“…Cadmium exposure is known to affect lipid metabolism even at low concentrations [39–41] and to cause a dose dependent increase in plasma triglyceride levels [42]. Using Oil-Red-O staining, which is able to dye neutral triglycerides and glycolipids, we found that cadmium induced lipid droplet accumulation that was not observed when cells were co-treated with OLE and cadmium (Fig 8A).…”