Malathion (MAL) exerts serious reproductive toxicity in males and leads to histopathological injuries in seminiferous tubules, sperm abnormalities, and hormonal disruptions such as reduced testosterone levels. The study assessed whether Lactobacillus acidophilus (L. acidophilus) supplementation could mitigate MAL-induced testicular damage via the crosstalk of cGAS/cGAMP/STING/NF-κB signaling, which in turn modulates the inflammatory cascades IRF3/IFN-β and TNFR/TNF-α, as well as the autophagic markers such as LC3-B/p62. The study also studied the role of miRNA-24 as an upstream regulator. The study included four groups: control, MAL-intoxicated group, L. acidophilus- and scopolamine-treated group. Seminal analysis and histopathological investigations of the testes were done. cGAS, STING, TNFR, IRF3, and miR-24 were estimated using qRT-PCR. cGAMP, IFN-β, LC3-B, and p62 were estimated using ELISA, whereas NF-κB and TNF-α were estimated using immunohistochemical analysis. MAL-intoxicated group showed altered seminal fluid analysis, higher gene expression of cGAS, STING, TNFR, and IRF3, along with lower gene expression of miRNA-24 compared with the control group. Moreover, the concentrations of cGAMP and IFN-β were higher, along with lower concentrations of testosterone, LC3-B, and p62, compared with the control group. Furthermore, NF-κB and TNF-α showed marked positive cytoplasmic expression. However, the L. acidophilus-treated group reversed all the above-mentioned findings. Collectively, the present study showed that MAL-exposure induces testicular toxicity via activating the cGAS/cGAMP/STING/IRF3/NF-κB/TNF-α axis, mediated by miRNA-24. L. acidophilus treatment alleviated these adverse effects, not only by restoring sperm quality, hormonal balance, and tissue architecture but also by suppressing the inflammatory signaling cascade, reactivating autophagic flux, and upregulating protective miRNA-24.
Abd-Elmawla et al. (Fri,) studied this question.