Background Mitochondrial complex ΙΙ has a unique biological role owing to its participation in both the citric acid cycle and the electron transport chain. Our goal was to evaluate the succinate dehydrogenase and ubiquinone oxidoreductase activity of mitochondrial complex II in the presence of chrysin and chrysin–chitosan nanoparticles. Chrysin chitosan nanoparticles were synthesized and characterized using ultraviolet spectroscopy, Fourier transform-infrared spectroscopy, X-ray diffraction, transmission electron microscopy, scanning electron microscopy, drug release, and zeta potential. The binding affinity of chrysin to complex II subunits was assessed by molecular docking. The IC50 values were measured in a suspension of mouse mitochondria, and the inhibitory effect of chrysin and chrysin chitosan nanoparticles on mitochondrial complex ΙΙ was determined. Results The free energy of binding between chrysin and complex ΙΙ subunits A, B, C, and D was −4.9, −5, −8.2, and −8.4 kcal/mol, respectively. The characteristic peak of chrysin was confirmed at 348 nm. The chrysin chitosan nanoparticles contained characteristic bands of both chrysin and chitosan. The crystalline nature of chrysin chitosan nanoparticles was confirmed by X-ray powder diffraction measurements showing the characteristic Bragg peaks of (11.2°), (32.2°), (19.6°), (27.6°), and (31.96°). Transmission and scanning electron microscopy revealed their spherical shape and an average particle size of 49.7 ± 3.02 nm. Chrysin chitosan nanoparticles showed a burst release within the initial 2 h followed by a steady release at 8 h. Their zeta potential was positive, between +35.5 and +80 mV. The IC50 of chrysin, chitosan nanoparticles, chrysin chitosan nanoparticles, and 5-fluorouracil was 34.66, 184.1, 12.2, and 0.05 μg/mL, respectively, in adult mice liver and 129, 311, 156, and 8.07 μg/mL, respectively, in normal human fibroblasts. When comparing the inhibitory effects on complex ΙΙ activity, application of the IC50 of chrysin, chitosan nanoparticles, chrysin chitosan nanoparticles, and 5-fluorouracil resulted in 40.14%, 90.9%, 86.7%, and 89% decreases in SDH activity and 70.09%, 86.74%, 60.8%, and 80.23% decreases in ubiquinone oxidoreductase activity in normal adult mice, but 80.9%, 89.06%, and 90% significant decreases in SDH activity, and 90%, 85%, and 95% decreases in ubiquinone reductase after treatment with chrysin, chrysin chitosan nanoparticles, and 5-fluorouracil, in normal human fibroblasts, respectively. Conclusions Chrysin and CCNPs exhibit potent inhibitory effects on SDH activity ubiquinone oxidoreductase activity.

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Cadmium (Cd) is one of the most dangerous occupational and environmental toxins. The objective of the present study is to examine the potential prophylactic effects of phytic acid (PA) on thyroid hormones of male rats intoxicated with Cd. The male albino rats were divided into five groups: group I (control) was fed with the basal diet, group II was intoxicated with Cd in drinking water, groups III, IV, and V were intoxicated with Cd in drinking water and fed with the diet containing 3.5, 7, and 10 g of PA/kg, respectively. The results indicated that the serum calcium, iron (Fe), and total Fe binding capacity levels and serum T3 and T4 in Cd-treated rats of group II were decreased when compared with the control group, while PA-administered groups with Cd showed a significant improvement when compared with the Cd-treated rats only. Serum thyroid stimulating hormone (TSH) level was significantly increased in Cd-treated rats compared with the control group, while the addition of PA in diet decreased the high levels of TSH. These results indicated a prophylactic effect of PA against Cd-induced toxicity in rats.

Background Flavonoids may help ameliorate the incidence of the major causes of tumor-related mortality, such as pancreatic ductal adenocarcinoma (PDAC) and lung cancer, which are predicted to steadily increase between 2020 to 2030. Here we compared the effect of chrysin and chrysin nanoparticles (CCNPs) with 5-fluorouracil (5-FLU) on the activity and expression of mitochondrial complex II (CII) to induce apoptosis in pancreatic (PANC-1) and lung (A549) cancer cells. Methods Chrysin nanoparticles (CCNPs) were synthesized and characterized, and the IC50 was evaluated in normal, PANC-1, and A549 cell lines using the MTT assay. The effect of chrysin and CCNPs on CΙΙ activity, superoxide dismutase activity, and mitochondria swelling were evaluated. Apoptosis was assessed using flow cytometry, and expression of the C and D subunits of SDH, sirtuin-3 (SIRT-3), and hypoxia-inducible factor (HIF-1α) was evaluated using RT-qPCR. Results The IC50 of CII subunit C and D binding to chrysin was determined and used to evaluate the effectiveness of treatment on the activity of SDH with ubiquinone oxidoreductase. Enzyme activity was significantly decreased (chrysin < CCNPs < 5-FLU and CCNPs < chrysin < 5-FLU, respectively), which was confirmed by the significant decrease of expression of SDH C and D, SIRT-3, and HIF-1α mRNA (CCNPs < chrysin < 5-FLU). There was also a significant increase in the apoptotic effects (CCNPs > chrysin > 5-FLU) in both PANC-1 and A549 cells and a significant increase in mitochondria swelling (CCNPs < chrysin < 5-FLU and CCNPs > chrysin > 5-FLU, respectively) than that in non-cancerous cells. Conclusion Treatment with CCNPs improved the effect of chrysin on succinate-ubiquinone oxidoreductase activity and expression and therefore has the potential as a more efficient formulation than chemotherapy to prevent metastasis and angiogenesis by targeting HIF-1α in PDAC and lung cancer.

A GING of cells is a normal feature but, it is important to delay this process and improve the life style. The present work aims at investigating the possible potential inhibitory effect of DL-β-hydroxybutyrate (βOHB) against hepatic cellular senescence induced by D-galactose or γ-irradiation in rats based on antioxidant and certain trace elements estimation in the liver. Six groups of male rats were used as follows: the control, irradiated group (acute dose 5 Gy, 2 weeks), D-galactose (150 mg/kg b.wt, 6 weeks), βOHB (72.8 mg/kg b.wt, 14 days), γ-irradiation plus βOHB, and D-galactose plus βOHB. Results show that neither βOHB nor D-galactose administration had a significant effect relative to the normal control value on Hb, MCV, and RBC's. βOHB along with D-galactose or γ-irradiation significantly increased G6PD activity compared with the control group. In D-galactose, or γ-irradiation groups, liver MDA levels and SOD activity were significantly increased. Meanwhile, NO and GSH levels were significantly increased in the γ-irradiation group relative to the normal control levels. The findings show that βOHB alleviated hematological, antioxidant alterations and modulated the change in Cu, Fe, and Zn elements in D-galactose or γ-irradiation group. The results concur well with histological alteration in our previous findings. It could be concluded that these findings highlight a role for βOHB as a potent protective agent against hepatic cellular senescence associated liver injury through enhancing RBC's G6PD activity, reduction of oxidative stress and partial modulation of trace elements.