Cisplatin (CP) is a cornerstone chemotherapeutic agent, however, its neurotoxicity is a chief cause of its limited usage. Linagliptin, which is a dipeptidyl peptidase‐4 enzyme inhibitor, has exhibited considerable neuroprotective potential. We aimed to evaluate the linagliptin modulatory effects on endoplasmic reticulum (ER) stress, redox status, and apoptosis in CP‐induced neurotoxicity. Thirty mice were allocated equally into the control group, Group II: CP group, and Group III: linagliptin treated CP group. All groups were subjected to the measurement of hippocampal messenger RNA gene expression of glucose‐regulated protein‐78 and C/EBP homologous protein (CHOP). Peroxisome proliferator‐activated receptor γ coactivator 1α and cleaved caspase‐3 levels were assessed by the enzyme‐linked immunosorbent assay technique while malondialdehyde, reduced glutathione levels and superoxide dismutase activity were detected spectrophotometrically. Linagliptin ameliorated ER stress and enhanced antioxidant status with cognitive function improvement. Linagliptin may be considered a promising neuroprotective agent owing to its ability to reduce ER/oxidative stress.
Troxerutin, a natural flavonoid guards against oxidative stress and apoptosis with a high capability of passing through the blood‐brain barrier. Our aim was to investigate the role of troxerutin in experimentally induced retinal neurodegeneration by modulating the interferon‐gamma (IFNγ)‐extracellular signal‐regulated kinases 1/2 (ERK1/2)‐CCAAT enhancer‐binding protein β (C/EBP‐β) signaling pathway. Three groups of rats (10 each group) were included. Group I (control group), group II (rotenone treated group): the rats were injected subcutaneously with a single rotenone dosage of 3 mg/kg repeated every 48 hours for 60 days to trigger retinal neurodegeneration. Group III (troxerutin‐treated group): rats received troxerutin (150 mg/kg/day) by oral gavage 1 hour before rotenone administration. A real‐time polymerase chain reaction technique was applied to measure messenger RNA (mRNA) levels of retinal C/EBP‐β. Enzyme‐linked immunosorbent assay technique was utilized to assay tumor necrosis factor‐α (TNF‐α), IFNγ, and ERK1/2 levels. Finally, reactive oxygen species (ROS), as well as carbonylated protein (CP) levels, were assessed spectrophotometrically. Improved retinal neurodegeneration by downregulation of C/EBP‐β mRNA gene expression, also caused a significant reduction of TNF‐α, IFNγ, ERK1/2 as well as ROS and CP levels compared with the diseased group. These findings could hold promise for the usage of troxerutin as a protective agent against rotenone‐induced retinal neurodegeneration.
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