Ferulic acid protects against gamma-radiation induced liver injury via regulating JAK/STAT/Nrf2 pathways.

This study aims to evaluate the effect and underlying mechanism of ferulic acid (FA) in alleviating the acute liver injury by ionizing radiation (IR) in vivo. Rats were divided into 4groups (Groups: control, 6Gy irradiated (IRR), FA (50 mg/kg) and FA + IRR). The results showed that FA can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, FA prevented IR-induced liver fibrosis and blocked the JAK/STAT signaling pathway to effectively inhibit the hepatic inflammatory response; and inhibited IR-induced oxidative stress (OS) by upregulating the Nrf2 signaling pathway and promoting the synthesis of several antioxidants. Moreover, FA inhibited ferroptosis in the liver by stimulating the expression of GPX4 and SLC7A11. FA reduced lipid peroxidation by downregulation of the reactive oxygen species (ROS) production and iron aggregation, thus inhibiting ferroptosis and alleviating IR-induced liver injury. In conclusion, the current study suggests the potential complex mechanisms underlying the mitigating impact of FA in IR-induced ferroptotic liver damage.

The potential effect of methylseleninic acid (MSA) against γ-irradiation induced testicular damage in rats: Impact on JAK/STAT pathway.

This study suggested that methylseleninic acid (MSA) could respond to the inflammatory signaling associated with ionizing radiation-induced testicular damage. Mature male rats were divided into four groups: negative control, whole body γ-irradiated (IRR) (5 Gy), MSA (0.5 mg/kg, daily for nine consecutive days), and MSA+ IRR groups. MSA increased serum testosterone level and testicular glutathione peroxidase (GPx) as well as decreased the percentage of sperm abnormalities. Radiation prompted inflammatory signaling in the testes through increasing phospho-janus kinase1 (p-JAK1), phospho-signal transducers and activators of transcription 3 (p-STAT3) protein expressions. This induced increment in the inflammatory markers including nuclear factor- kappa B (NF-κB) and interleukin-1beta (IL-1ß) levels. Also, radiation induced elevation of nitric oxide (NO) and malondialdhyde (MDA) levels with consequent reduction in testicular reduced glutathione level (GSH) and superoxide dismutase (SOD) activity. MSA significantly counteracted the radiation effect on testicular nuclear factor erythroid-2-related factor-2 (Nrf2) and suppressor of cytokine signaling (Socs3) protein expressions. In summary, this investigation proposed that MSA preserved spermatogenesis through increasing testosterone levels and GPx activity. Additionally, it diminished testicular inflammation by increasing of Nrf2 and Socs3 levels leading to reducing of p-JAK1, p-STAT3 and NF-κB levels. Histopathological examination results of testicular tissues showed a coincidence with the biochemical analysis.

Ferulic acid protects against radiation-induced testicular damage in male rats: impact on SIRT1 and PARP1.

Ionizing radiation is a major contributor to male infertility by destroying spermatogenesis. Therefore, the need for an effective radio-protective agent is evident. The objective of the present study was to investigate the potential radio-protective effect of ferulic acid (FA) on radiation-induced testicular damage. Mature male Sprague-Dawley rats were either exposed to a single-dose gamma radiation (5 Gy) and/or treated with FA (50 mg/kg), daily for 7 days before irradiation. Sirtuin1 (SIRT1), poly (ADP-ribose) polymerase 1 (PARP1), cytosolic calcium content, and the male reproductive functions (sperm head abnormality) as well as oxidative stress markers were assessed 7 days after irradiation. FA significantly maintained active spermatogenesis. Moreover, it reversed the oxidative stress effects of irradiation. The irradiated group showed marked elevation in both PARP1 expression and activity as well as in cytosolic calcium concentration, whereas SIRT1 activity and expression markedly decreased; in contrast, FA treatment prevented these alterations. Results of histopathological examination of testicular tissues indicated coincidence with those recorded by biochemical analyses. Our data show for the first time that FA had radio-protective effect against radiation-induced testicular damage. It improved spermatogenesis through increasing testicular SIRT1 and testosterone levels and decreasing oxidative stress, PARP1, and cytosolic calcium.