chrysin and Reperfusion-Injury

Chrysin is a natural flavonoid compound that has antioxidant and neuroprotective effects. Cerebral ischemia reperfusion (CIR) is closely connected with increased oxidative stress in the hippocampal CA1 region and homeostasis disorder of transition elements such as iron (Fe), copper (Cu) and zinc (Zn). This exploration was conducted to elucidate the antioxidant and neuroprotective effects of chrysin based on transient middle cerebral artery occlusion (tMCAO) in rats. Experimentally, sham group, model group, chrysin (50.0 mg/kg) group, Ginaton (21.6 mg/kg) group, Dimethyloxallyl Glycine (DMOG, 20.0 mg/kg) + chrysin group and DMOG group were devised. The rats in each group were performed to behavioral evaluation, histological staining, biochemical kit detection, and molecular biological detection. The results indicated that chrysin restrained oxidative stress and the rise of transition element levels, and regulated transition element transporter levels in tMCAO rats. DMOG activated hypoxia-inducible factor-1 subunit alpha (HIF-1α), reversed the antioxidant and neuroprotective effects of chrysin, and increased transition element levels. In a word, our findings emphasize that chrysin plays a critical role in protecting CIR injury via inhibiting HIF-1α against enhancive oxidative stress and raised transition metal levels.

Topics: Animals; Antioxidants; Brain Ischemia; Flavonoids; Hippocampus; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury; Transition Elements

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.

Topics: Animals; Brain Ischemia; Cerebral Infarction; Cyclooxygenase 2; Ferroptosis; Infarction, Middle Cerebral Artery; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Reperfusion Injury; RNA, Messenger; Signal Transduction

The chrysin has properties of low aqueous solubility, bioavailability and absorption, and its effect on hepatic ischaemia-reperfusion (HIR) remains unclear. Thus, we prepared a liposomal chrysin (LC) and explored its effect and potential mechanism on HIR.. A thin-film dispersion method was used to prepare LC, and a mouse HIR model was used. Mice were pre-treated with LC (100 mg/kg) or placebo by gavage feeding at 16.5 h, 8.5 h, 0.5 h before modelling.. The average particle sizes, polydispersity index, zeta potential, encapsulation efficiency and drug loading of LC were 129 ± 13.53 nm, 0.265 ± 0.021, -34.46 ± 4.14 mV, 95.03 ± 2.17%, 16.4 ± 0.8%. The concentration of chrysin in plasma and liver tissue by LC administration increased 2.54 times and 1.45 times. LC pre-treatment reduced HIR-induced liver injury and inhibited cell apoptosis. Besides, LC pre-treatment decreased reactive oxygen species and malondialdehyde and inhibited the inflammation response indicated by lower IL-6, TNF-α, infiltration of neutrophils. Further, LC pre-treatment significantly decreased NLRP3 activation, evidenced by reduced cleaved caspase-3, NLRP3, ASC, cleaved caspase-1 and IL-1β expression.. LC has good biocompatibility, and it could attenuate HIR-induced injury. Its mechanism was associated with NLRP3 inflammasome inhibition, and LC might be an effective drug for treating and preventing HIR-induced injury.

Topics: Animals; Apoptosis; Disease Models, Animal; Flavonoids; Inflammasomes; Liposomes; Liver Diseases; Male; Mice; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; Particle Size; Reactive Oxygen Species; Reperfusion Injury

The purpose of this study was to evaluate the possible therapeutic effect of chrysin (CHS) on testicular torsion/detorsion (T/D) injury. Eighteen male rats were divided into three groups of six subjects in each group: control, T/D and T/D + CHS (100 mg/kg). To evaluate the degree of oxidative stress, tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods, while tissue superoxide dismutase (SOD) levels were determined using an ELISA kit. To evaluate the degree of ERS, tissue glucose regulatory protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) levels were determined using ELISA kits. Johnsen's testicle scoring system was used for histological evaluation.. In the T/D group, it is determined that statistically significant decreasing in the levels of TAS, SOD and Johnsen score, and increasing in TOS, MDA, GRP78, ATF6 and CHOP levels compared to control group (p < 0.05). CHS administration statistically significantly restored this T/D-induced damage (p < 0.05).. This is the first study to show that CHS prevent T/D-induced testicular damage through its ERS inhibitor activity. More comprehensive studies are needed to understand the underlying mechanisms.. Supplemental data for this article is available online at https://doi.org/10.1080/08941939.2021.2015489 .

Topics: Animals; Antioxidants; Endoplasmic Reticulum Stress; Flavonoids; Humans; Male; Malondialdehyde; Oxidative Stress; Rats; Reperfusion Injury; Spermatic Cord Torsion; Superoxide Dismutase

This study was performed to evaluate the effect of chrysin on testicular torsion and detorsion damage in rats in terms of biochemistry, histopathology and immunohistochemistry. The study was performed on Wistar albino rats between 250 g and 300 g. A total of 40 rats were used. Five groups were created with eight rats in each group. Group 1 was the control group, and no torsion procedure was performed. In Group 2, 2 hr of torsion and 2 hr of detorsion were applied. In Group 3, 2 hr of torsion and 24 hr of detorsion were applied. In Group 4, 2 hr of torsion, 2 hr of detorsion and 50 mg/kg intraperitoneal chrysin were applied. In Group 5, 2 hr of torsion, 24 hr of detorsion and 50 mg/kg of chrysin were applied. In the torsion/detorsion groups, the study determined decreases in glutathione and testosterone levels, increases in tumour necrosis factor-α, interleukin-4, interleukin-6 and interleukin-10 levels, and increases in expression levels of caspase-3 and caspase-8. Chrysin application reduced malondialdehyde, tumour necrosis factor-α, caspase-3 and caspase-8 expression levels. We can say that chrysin can be used to reduce damage in cases of testicular ischaemia/reperfusion. For more reliable results, further clinical trials are recommended.

Topics: Animals; Flavonoids; Humans; Male; Malondialdehyde; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury; Spermatic Cord Torsion; Testis

Ischemic stroke is one of the leading causes of death worldwide, and extensive efforts have focused on the neuroprotective strategies to minimize complications due to ischemia. This study aimed to examine neuroprotective potential of chrysin, as a natural potent antioxidative and anti-inflammatory agent in an animal model of bilateral common carotid artery occlusion and reperfusion (BCCAO/R).. Adult male Wistar rats (250-300 g) were randomly divided into 6 groups and submitted to either sham surgery or BCCAO/R after pretreatment with chrysin (10, 30 and 100 mg/kg, once daily, for 21 consecutive days) or saline containing %5 DMSO. To make the animal model of BCCAO/R, bilateral common carotid arteries were occluded for 20 min, followed by reperfusion. Subsequently, spatial cognitive performance was evaluated in a Morris water maze (MWM), hippocampal long-term potentiation (LTP) was recorded from hippocampal dentate gyrus region, after then the hippocampal tissue content of IL-1β and TNF-α were assayed using ELISA kits.. The results showed that pretreatment with chrysin significantly prevented BCCAO/R-induced cognitive and hippocampal LTP impairments (p < 0.001). Additionally, BCCAO/R- induced elevation in hippocampal content of IL-1β and TNF-α significantly (p < 0.01, p < 0.01 respectively) while pre-treatment with chrysin restored them (p < 0.01).. Our data confirm that chrysin could prevent brain inflammation and thereby prevents cognitive and LTP impairments due to cerebral ischemia. So it could be a promising neuroprotective agent against cerebrovascular insufficiency states.

Topics: Animals; Antioxidants; Brain Ischemia; Carotid Arteries; Carotid Artery, Common; Cognition; Cognitive Dysfunction; Disease Models, Animal; Encephalitis; Flavonoids; Hippocampus; Inflammation; Long-Term Potentiation; Male; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Wistar; Reperfusion Injury

In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTOR pathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.

Topics: Animals; Apoptosis; Brain Edema; Cell Line; Clopidogrel; Drug Evaluation, Preclinical; Flavonoids; Infarction, Middle Cerebral Artery; Inflammation; Interleukin-1beta; Interleukin-6; Male; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Superoxide Dismutase-1; TOR Serine-Threonine Kinases; Tumor Necrosis Factor-alpha

The present study investigated the neuroprotective effects of chrysin (CRS) following global cerebral ischemia and reperfusion (I/R) in a C57BL/J6 mouse model.. A total of 40 mice were equally divided into four groups: (1) sham-operated (SH = control), (2) global cerebral I/R (I/R), (3) CRS, and (4) CRS + I/R. In the I/R group, the bilateral carotid arteries were clipped for 15 min and the mice were treated with vehicle (corn oil) for 10 days. In the CRS group, CRS (50 mg/kg) was given for 10 days without carotid occlusion. In the CRS + I/R group bilateral carotid arteries were clipped for 15 min and the mice were also treated with CRS (50 mg/kg) for 10 days. All of the rats were sacrificed under anesthesia on day 10, and neurodegenerative histological changes in the brain and tissue levels of oxidants and antioxidants were evaluated.. CRS treatment significantly reversed the oxidative effects of I/R and inhibited the development of neurodegenerative histopathologies. In the CRS + I/R group, the decrease in TBARS levels and increase in GSH levels were similar to those in the SH group.. Treatment with CRS can positively affect the neural system of mice and it can be used for the treatment of global cerebral I/R.

Topics: Animals; Brain; Brain Ischemia; Flavonoids; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Rats; Reperfusion Injury

Inflammation and oxidative stress play an important part in the pathogenesis of focal cerebral ischemia/reperfusion (I/R) injury, resulting in neuronal death. The signaling pathways involved and the underlying mechanisms of these events are not fully understood. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. In this study, we investigated the neuroprotective properties of chrysin in a mouse model of middle cerebral artery occlusion (MCAO). To this end, male C57/BL6 mice were pretreated with chrysin once a day for seven days and were then subjected to 1 h of middle cerebral artery occlusion followed by reperfusion for 24 h. Our data show that chrysin successfully decreased neurological deficit scores and infarct volumes, compared with the vehicle group. The increases in glial cell numbers and proinflammatory cytokine secretion usually caused by ischemia/reperfusion were significantly ameliorated by chrysin pretreatment. Moreover, chrysin also inhibited the MCAO-induced up-regulation of nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the vehicle. These results suggest that chrysin could be a potential prophylactic agent for cerebral ischemia/reperfusion (I/R) injury mediated by its anti-inflammatory and anti-oxidative effects.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Brain Ischemia; Cytokines; Flavonoids; Infarction, Middle Cerebral Artery; Inflammation; Male; Mice, Inbred C57BL; Middle Cerebral Artery; Neuroprotective Agents; Oxidative Stress; Reperfusion Injury