Scutellarin alleviates lipopolysaccharide-provoked septic nephrotoxicity via attenuation of inflammatory and oxidative events and mitochondrial dysfunction.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) is highlighted by high incidence of mortality and morbidity. Scutellarin is a flavone extracted from certain medicinal plants with anti-inflammatory and anti-oxidative properties. This research study was done to investigate the beneficial effect of scutellarin on lipopolysaccharide (LPS) murine model of AKI. MATERIALS AND METHODS: Five groups of mice were used including control (without LPS injection), LPS group (LPS injection, 10 mg/kg), and LPS + Scutellarin25, 50, and/or 100 groups (receiving scutellarin orally at different doses of 25, 50, or 100 mg/kg before LPS injection). RESULTS: Scutellarin pretreatment effectively lowered kidney function markers (BUN, creatinine, and cystatin C), improved superoxide dismutase (SOD) besides enhancement of level, and/or gene expression for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) and also reduced oxidative stress factors including reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, scutellarin reduced tissue level and/or gene expression of inflammatory markers comprising toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), and tumor necrosis factor α (TNF-α) and properly raised anti-inflammatory factor IL-10. Moreover, scutellarin enhanced mitochondrial membrane potential (MMP) and attenuated histopathological changes in renal tissue subsequent to LPS challenge. Beneficial effects of scutellarin was associated with improvement of gene expression regarding peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PGC-1α as specific markers of mitochondrial biogenesis. CONCLUSION: These results indicate that scutellarin could protect against LPS-provoked AKI through restraining inflammation and oxidative stress and maintenance of mitochondrial health and biogenesis which is partly mediated through its regulation of Nrf2/PPAR-γ/PGC-1α/NF-kB/TLR4.

Dendritic spine changes in medial prefrontal cortex of male diabetic rats using Golgi-impregnation method.

BACKGROUND: Neuropathy is one of the major complications contributing to morbidity in patients with diabetes mellitus. The effect of diabetes on brain has not been studied so much and no gross abnormality has been found in the central nervous system of patients with diabetic neuropathy. This study was conducted to evaluate the time-dependent structural changes in medial prefrontal cortex of male diabetic rats using Golgi-impregnation method. METHODS: Male Wistar rats were randomly divided into the control and diabetic groups. For induction of diabetes, a single dose of streptozotocin (60 mg/kg) was injected intraperitoneally. At the end of the first and second months, the rats were transcardially perfused with a solution of phosphate buffer containing paraformaldehyde and Golgi-impregnated method was used to evaluate the changes of dendritic spines in medial prefrontal cortex. RESULTS: There was a significant reduction in the mean density of pyramidal neuron dendritic spines in the layers II and III of medial prefrontal cortex only after 2 months in the diabetic group compared to age-matched controls (P < 0.05). CONCLUSION: Diabetes induces a reduction in the spine density of apical dendrites of medial prefrontal cortex only in two-month diabetic rats.