Contribution of Oxidative Stress, Apoptosis, Endoplasmic Reticulum Stress and Autophagy Pathways to the Ameliorative Effects of Hesperidin in NaF‐Induced Testicular Toxicity

Abstract

The ameliorative effects of hesperidin (HES) on the toxicities created by sodium fluoride (NaF) in the testes tissue of rats were studied via oxidative stress, apoptosis and endoplasmic reticulum (ER) stress pathways. The animals were divided into five distinct groups (7 rats in each group). Group 1 was control group, group 2 received NaF-only (600 ppm), group 3 received HES-only (200 mg/kg bw); group 4 received NaF (600 ppm) + HES (100 mg/kg bw) and group 5 received NaF (600 ppm) + HES (200 mg/kg bw) for 14 days. NaF-induced testes tissue damage by reducing activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and levels of glutathione (GSH), and increasing lipid peroxidation levels. NaF treatment significantly downregulated the mRNA levels of SOD1, CAT and GPx. NaF supplementation caused apoptosis in the testes by upregulating p53, NFkB, caspase-3, caspase-6, caspase-9, and Bax and downregulating Bcl-2. Furthermore, NaF caused ER stress via increasing mRNA transcript levels of PERK, IRE1, ATF-6 and GRP78. NaF treatment led to autophagy via upregulation of Beclin1, LC3A, LC3B and AKT2. In testes tissue, however, co-treatment with HES at doses of 100 and 200 mg/kg significantly reduced oxidative stress, apoptosis, autophagy and ER stress. Overall, the findings of this study suggest that HES may help to reduce testes damage caused by NaF toxicity.

Caffeic acid phenethyl ester mediates apoptosis in serum‐starved HT29 colon cancer cells through modulation of heat shock proteins and MAPK pathways

“…35 Moreover, the anticancer effects of certain cancer drugs, such as cisplatin, 36 38 Prior research has demonstrated antioxidant effectiveness in preventing cancer cell growth and their roles in apoptosis. 39,40 With this idea, we addressed the molecular bases of CAPE-induced apoptosis by first evaluating possible changes in ROS levels and ΔΨM. ROS serve as precursors that trigger antioxidant response elements, 24 and previous studies have linked CAPE exposure to ROS formation.…”

“…For instance, although anticancer therapy‐induced apoptosis might eradicate cancer cells, sublethal activation of caspase 3 may cause neoplastic development because inadequate apoptosis induction can activate survival mechanisms like autophagy 38 . Prior research has demonstrated antioxidant effectiveness in preventing cancer cell growth and their roles in apoptosis 39,40 . With this idea, we addressed the molecular bases of CAPE‐induced apoptosis by first evaluating possible changes in ROS levels and ΔΨM.…”

Naringin protects against paclitaxel‐induced toxicity in rat testicular tissues by regulating genes in pro‐inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways

“…[ 78 ] In case of an imbalance in the Bax/Bcl‐2 ratio, p53 may further increase the amount of cytochrome c released into the cytoplasm by changing the level of Bcl‐2 family proteins. [ 79 ] Cytochrome c, which passes into the stasis, binds to APAF‐1 and activates Caspase‐9. Subsequently, Caspase‐9 activates Caspase‐3 as an apoptotic factor.…”

The Protective Effects of Water-Soluble Alginic Acid on the N-Terminal of Thymopentin

“…They can be proteins or peptides secreted by different cell types, including immune cells, in response to diverse stimuli such as infections, injuries, or immune responses. Examples of cytokines encompass interleukins (IL-2, IL-6, IL-8, IL-12), TNF-α, and IFNs [ 43 , 44 , 45 ]. TNF-α participates in the destruction of tumor cell structure and the induction of cell apoptosis and may serve as a co-stimulatory factor for mitogen-activated normal B cells [ 46 ].…”