Research Information System
CHEMICO-BIOLOGICAL INTERACTIONS, vol.424, 2026 (SCI-Expanded, Scopus)
5-Hydroxymethylfurfural (HMF) is a heat-induced food contaminant commonly present in processed products and regularly ingested through the diet. Although its genotoxic, neurotoxic, and carcinogenic effects have been demonstrated in various tissues, the cellular effects of HMF on the male reproductive system are still not sufficiently elucidated. For the first time, this study comprehensively evaluated the toxic effects of HMF on Sertoli (TM4) and type B spermatogonium (GC-1) cell lines. HMF was administered to TM4 and GC-1 cells at concentrations of 0.1, 1, and 10 mM for 24 h. The findings revealed that HMF caused concentration-dependent cytotoxicity in both cell types. HMF was found to cause significant increases in total reactive oxygen species and lipid peroxidation levels in germ cells. Gene expression analyses indicated disruptions in the Nrf2, Keap1, and Parp1 genes that affect cell defense mechanisms. HMF exposure led to significant increases in Trp53, Bax, and Casp3 gene expression, a decrease in the anti-apoptotic Bcl2 gene, and elevated CASP3 protein levels in both cell lines. Furthermore, significant increases in autophagy-related Atg5, Lc3a/b, and Beclin-1 genes and proteins were observed following HMF administration. Also, our study demonstrated that the PI3K/AKT/mTOR signaling pathway was suppressed, and cellular death mechanisms were modulated through this pathway. Our results suggest that the toxic effects of HMF vary depending on the cell type and elicit a more pronounced response, particularly in GC-1 cells. In conclusion, HMF can cause cytotoxic effects in male germ cells by activating oxidative stress, apoptosis, and autophagy pathways.