Tissue Damage In Rats Research Articles

The effect of melatonin and probiotics on radiation-induced enteritis in experimental rat models

Radiotherapy plays an important role in the treatment of tumors, and enteritis is a common side effect of this therapy. The aim of present study was to evaluate the protective effect of melatonin and probiotics on radiation-induced intestinal tissue damage in rats. Histopathological, biochemical and microbiological samples were examined. Thirty-two Wistar Albino rats were randomly distributed into four groups: the control group, only radiotherapy (RT) group, radiotherapy plus melatonin (RT + MEL) groups and radiotherapy plus probiotics (RT + PROB) groups. The abdominal-pelvic region of the experimental rat was irradiated with in a single dose of 16 Gy. The melatonin was administered at a single dose of 50 mg/kg through intraperitoneal injection, 15 min before radiation exposure. The probiotic was administered orally every day to the rats for 5 days starting before radiotherapy. There was a statistically significant changes in histopathological (villus atrophy, mitotic activity, apoptotic index, goblet cell swelling, degenerative changes, atypia) and biochemical (oxidant and antioxidant status, IL-1β, IL-6 and TNF- α levels) parameters in the small intestine in the radiotherapy group G2 compared to the G1 control group (p < 0.05). However, a significant decrease was observed with the administration of probiotics and melatonin (p < 0.05). In addition, although positive bacterial growth was detected in the mesenteric lymph node of all rats in the radiotherapy group, there was no statistically significant difference between all groups (p > 0.05). Melatonin and probiotics were found to have a potent radioprotective effect against radiotherapy-induced acute small intestinal tissue damage. However, their superiority over each other was not observed.

Ferrostatin-1 ameliorates Cis-dichlorodiammineplatinum(II)-induced ovarian toxicity by inhibiting ferroptosis

Cis-dichlorodiammineplatinum(II) (CDDP), while widely utilized in tumor therapy, results in toxic side effects that patients find intolerable. The specific mechanism by which CDDP inflicts ovarian damage remains unclear. This study aimed to explore the involvement of ferrostatin-1 (FER-1) and ferroptosis in CDDP-induced ovarian toxicity. This study established models of CDDP-induced injury in granulosa cells (GCs) and rat model of premature ovarian failure (POF). CCK-8 assessed the effects of CDDP and FER-1 on GC viability. FerroOrange and Mito-FerroGreen, DCFH-DA and MitoSox-Red, Rhodamine 123 and Transmission electron microscopy (TEM) measured Fe2+, reactive oxygen species (ROS), mitochondrial membrane potential and the mitochondrial morphology in GC cells, respectively. Serum hormone levels; organ indices; malondialdehyde, superoxide dismutase, and glutathione analyses; and western blotting were performed to examine ferroptosis's role in vitro. Molecular docking simulation was evaluated the interaction between FER-1 and GPX4 or FER-1 and NRF2. Molecular docking simulations were conducted to evaluate the interactions between FER-1 and GPX4, as well as FER-1 and NRF2. The findings revealed that CDDP-induced ovarian toxicity involved iron accumulation, increased ROS accumulation, and mitochondrial dysfunction, leading to endocrine disruption and tissue damage in rats. These changes correlated with NRF2, HO-1, and GPX4 levels. However, FER-1 decreased the extent of ferroptosis. Thus, ferroptosis appears to be a crucial mechanism of CDDP-induced ovarian injury, with GPX4 as potential protective targets.

Berberine hydrochloride-loaded lipid-based nanoparticles ameliorate β-cell function by targeting Nrf2/NF-κB signaling pathway in alloxan-induced diabetes using a murine model: Optimization through full factorial design

Berberine hydrochloride (BH), a naturally occurring alkaloid having pleiotropic biological effects, is characterized by high water solubility, poor bioavailability, and a brief half-life. The objective of this study was to develop a liposomal formulation of BH that is more accessible and to ascertain whether its intraperitoneal administration might mitigate pancreatic tissue damage in rats that have been induced by alloxan. Rats were divided into four groups: control, alloxan, metformin, and BH-liposomes (BH-Lip). Measurements of blood glucose, insulin, pancreatic antioxidant state, and pro-inflammatory mediators were used to assess the severity of pancreatic injury in rats among all groups. According to the results, BH-Lip reduced the extent of alloxan-induced pancreatic tissue damage in rats, as demonstrated by improved HOMA-IR and HOMA-β scores, insulin, total pancreatic antioxidant capacity, and lower blood glucose levels. Furthermore, BH-Lip boosted the antioxidant transcription factor Nrf2 and downregulated the mRNA expression of pancreatic pro-inflammatory mediators, such as NF-κB and NLRP3. Moreover, immuno-histochemical labeling revealed that BH-Lip inhibited the protein transcription of caspase-3 and TNF-α in the pancreatic tissues of alloxan-treated rats. These findings provide BH-Lip as a safe substitute for traditional antidiabetics by reducing pancreatic tissue damage caused by alloxan via targeting the Nrf2/NF-κB pathway.

Effects of prolonged hydroxychloroquine use on the pancreatic tissue and expected ameliorative effect of lactoferrin in rats (biochemical, histological, and morphometric study)

Hydroxychloroquine (HCQ), an antimalarial drug widely used in treating rheumatoid disorders. Many side effects have been reported with HCQ administration indicating its hazardous effects on various organs. No previous studies reported the effect of long-term administration of oral HCQ on pancreatic tissue. Our study assessed pancreatic tissues functional and histopathological alterations following prolonged oral administration of HCQ. We also investigated the possible ameliorative effects of the lactoferrin (LF) coadministration with HCQ in adult male albino rats. Forty adult male Wister albino rats were divided into: negative control, LF positive control (2 g/kg), HCQ-treated (200 mg/kg), and HCQ+LF treated. Biochemical, histological, immunohistochemical, and morphometric analyses of the pancreatic tissues were conducted. Our findings revealed that prolonged oral administration of HCQ induced significant disruption of the pancreatic acinar architecture, enlarged congested islets of Langerhans, and elevated plasma insulin, amylase, and lipase levels. Interestingly, LF administration ameliorated the deleterious effects of prolonged HCQ administration on pancreatic tissue of adult male albino rats. In conclusion, prolonged oral administration of HCQ induced pancreatic tissue damage in rats, while LF attenuates HCQ-induced pancreatic injury. Our results emphasized the necessity of prescribing HCQ with caution, considering both dosage and treatment duration.

N6-Methyladenosine Demethylase ALKBH5 Promotes Pyroptosis by Modulating PTBP1 mRNA Stability in LPS-Induced Myocardial Dysfunction.

This study aims to investigate the mechanism by which alkB homolog 5 (ALKBH5) regulates polypyrimidine tract-binding protein 1 (PTBP1) to mediate cardiomyocyte pyroptosis in sepsis-induced myocardial injury. Lipopolysaccharide (LPS)-exposed H9C2 cell and rat models were established to mimic septic myocardial injury both in vitro and in vivo. The mRNA and protein levels of ALKBH5 and PTBP1 in the LPS-induced cell and septic rat models were detected. CCK-8 and flow cytometry were applied to detect cell viability and pyroptosis. H&E staining was used to observe myocardial tissue damage in rats, and immunohistochemistry to analyze the expression of pyroptosis and inflammation-related proteins in rat tissues. Elevated expressions of both ALKBH5 and PTBP1 were found in the myocardial tissues of LPS-induced septic rats. ALKBH5 knockdown could restore the cell viability and cell pyroptosis inhibited by LPS, while ALKBH5 promoted PTBP1 mRNA stability by affecting its N6-methyladenosine (m6A) modification. In vivo experiments showed that PTBP1 knockdown could largely reverse the antiproliferative and pro-pyroptosis effects of ALKBH5 in LPS-exposed H9C2 cells. ALKBH5 knockdown in in vivo experiments was found to suppress the expressions of pyroptosis biomarkers and attenuate myocardial injury in septic rats. ALKBH5 promoted mRNA stability and the expression of PTBP1 through m6A modification to induce pyroptosis in cardiomyocytes and ultimately aggravate sepsis-induced myocardial dysfunction.

Mesenchymal stem cell-derived exosomes promote tissue repair injury in rats with liver trauma by regulating gut microbiota and metabolism

ObjectiveThe effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed. MethodsAdult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis. ResultsRats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota, Proteobacteria, and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas, Alistipes, Aerococcus, Faecalibaculum, and Lachnospiraceae_ND3007_group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas/Faecalibaculum and inflammatory cytokines. ConclusionMSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma.

The role of FPR2-mediated ferroptosis in formyl peptide-induced acute lung injury against endothelial barrier damage and protective effect of the mitochondria-derived peptide MOTS-c

BackgroundAcute lung injury (ALI) has garnered significant attention in the field of respiratory and critical care due to its high mortality and morbidity, and limited treatment options. The role of the endothelial barrier in the development of ALI is crucial. Several bacterial pathogenic factors, including the bacteria-derived formyl peptide (fMLP), have been implicated in damaging the endothelial barrier and initiating ALI. However, the mechanism by which fMLP causes ALI remains unclear. In this study, we aim to explore the mechanisms of ALI caused by fMLP and evaluate the protective effects of MOTS-c, a mitochondrial-derived peptide. MethodsWe established a rat model of ALI and a human pulmonary microvascular endothelial cell (HPMVEC) model of ALI by treatment with fMLP. In vivo experiments involved lung histopathology assays, assessments of inflammatory and oxidative stress factors, and measurements of ferroptosis-related proteins and barrier proteins to evaluate the severity of fMLP-induced ALI and the type of tissue damage in rats. In vitro experiments included evaluations of fMLP-induced damage on HPMVEC using cell activity assays, assessments of inflammatory and oxidative stress factors, measurements of ferroptosis-related proteins, endothelial barrier function assays, and examination of the key role of FPR2 in fMLP-induced ALI. We also assessed the protective effect of MOTS-c and investigated its mechanism on the fMLP-induced ALI in vivo and in vitro. ResultsResults from both in vitro and in vivo experiments demonstrate that fMLP promotes the expression of inflammatory and oxidative stress factors, activates ferroptosis and disrupts the vascular endothelial barrier, ultimately contributing to the development and progression of ALI. Mechanistically, ferroptosis mediated by FPR2 plays a key role in fMLP-induced injury, and the Nrf2 and MAPK pathways are involved in this process. Knockdown of FPR2 and inhibition of ferroptosis can attenuate ALI induced by fMLP. Moreover, MOTS-c could protect the vascular endothelial barrier function by inhibiting ferroptosis and suppressing the expression of inflammatory and oxidative stress factors through Nrf2 and MAPK pathways, thereby alleviating fMLP-induced ALI. ConclusionOverall, fMLP disrupts the vascular endothelial barrier through FPR2-mediated ferroptosis, leading to the development and progression of ALI. MOTS-c demonstrates potential as a protective treatment against ALI by alleviating the damage induced by fMLP.

Chinmedomics strategy for elucidating the effects and effective constituents of Danggui Buxue Decoction in treating blood deficiency syndrome.

Danggui Buxue Decoction (DBD) is a clinically proven, effective, classical traditional Chinese medicine (TCM) formula for treating blood deficiency syndrome (BDS). However, its effects and effective constituents in the treatment of BDS remain unclear, limiting precise clinical therapy and quality control. This study aimed to accurately evaluate the effects of DBD and identify its effective constituents and quality markers. BDS was induced in rats by a combined injection of acetylphenylhydrazine and cyclophosphamide, and the efficacy of DBD against BDS was evaluated based on body weight, body temperature, energy metabolism, general status, visceral indices, histopathology, biochemical markers, and metabolomics. The effects of DBD on urinary and serum biomarkers of BDS were investigated, and the associated metabolic pathways were analyzed via metabolomics. Guided by Chinmedomics, the effective constituents and quality markers of DBD were identified by analyzing the dynamic links between metabolic biomarkers and effective constituents in vivo. DBD improved energy metabolism, restored peripheral blood and serum biochemical indices, and meliorated tissue damage in rats with BDS. Correlation analyses between biochemical indices and biomarkers showed that 15(S)-HPETE, LTB4, and taurine were core biomakers and that arachidonic acid, taurine, and hypotaurine metabolism were core metabolic pathways regulated by DBD. Calycosin-7-glucoside, coumarin, ferulic acid sulfate, cycloastragenol, (Z)-ligustilide + O, astragaloside IV, acetylastragaloside I, and linoleic acid were identified as effective constituents improving the hematopoietic function of the rats in the BDS model. Additionally, calycosin-7-glucoside, ferulic acid, ligustilide, and astragaloside IV were identified as quality markers of DBD. The hematopoietic function of DBD was confirmed through analysis of energy metabolism, biochemical markers, histopathology, and metabolomics. Moreover, by elucidating effective constituents of DBD in BDS treatment, quality markers were confirmed using a Chinmedomics strategy. These results strengthen the quality management of DBD and will facilitate drug innovation.

Subchronic exposure to fenpyroximate causes multiorgan toxicity in Wistar rats by disrupting lipid profile, inducing oxidative stress and DNA damage

Background Fenpyroximate (FEN) is an acaricide that inhibits the complex I of the mitochondrial respiratory chain in mites. Data concerning mammalian toxicity of this acaricide are limited; thus the aim of this work was to explore FEN toxicity on Wistar rats, particularly on cardiac, pulmonary, and splenic tissues and in bone marrow cells. Methods rats were treated orally with FEN at 1, 2, 4, and 8 mg/Kg bw for 28 days. After treatment, we analyzed lipid profile, oxidative stress and DNA damage in rat tissues. Results FEN exposure increased creatinine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, elevated total cholesterol (T-CHOL), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) concentrations, while decreasing high-density lipoprotein cholesterol (HDL-C). It inhibited acetylcholinesterase (AChE) activity, enhanced lipid peroxidation, protein oxidation, and modulated antioxidant enzymes activities (superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase). Comet assay indicated that FEN induced a dose-dependent DNA damage, contrasting with the micronucleus test showing no micronuclei formation. Nonetheless, FEN exhibited cytotoxicity to bone marrow cells, as evidenced by a reduction in the number of immature erythrocytes among total cells. Conclusion FEN appears to carry out its genotoxic and cytotoxic activities most likely through an indirect pathway that involves oxidative stress.

Long-term effects of warm water immersion on kidney tissue damage in diabetic rats.

This study aimed to investigate the effects of Warm Water Immersion (WWI) on inflammation, kidney function, and kidney tissue damage in rats with diabetes mellitus (DM). Forty male rats were divided into four groups: Healthy Control (HC), Diabetic Control (DC), Diabetic Rats treated with WWI (DW), and Healthy Rats treated with WWI (HW). Daily 15-minute WWI sessions at 43 °C were administered for eight weeks. Various parameters including lipids, fasting blood sugar (FBS), HbA1C, insulin, advanced glycation end products (AGEs), HSP70, glomerular filtration rate (GFR), urinary albumin excretion, creatinine, blood urea nitrogen (BUN), oxidative stress, anti-oxidant parameters, and gene expression of RAGE, VEGF, and TGFß1 were assessed. Histological examination of kidney tissue was also conducted. Significant reductions in FBS, AGEs, glutathione, superoxide dismutase (SOD), and nitric oxide (NO) levels were observed in the DW group compared to DC. Expression of RAGE, VEGF, and TGFß1 genes decreased in DW. Triglycerides, total cholesterol, and LDL cholesterol were lower in DW. Insulin, HDL cholesterol, catalase, total anti-oxidant capacity (TAC), and tissue HSP70 were higher in DW. Histological assessment revealed reduced kidney damage in DW compared to DC. WWI for eight weeks shows promise in mitigating diabetic nephropathy in rats, suggesting its potential as a non-invasive adjunctive therapy for managing diabetes complications.

PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis.

Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) induction. The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression. Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival. Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.

Effects of Cyfluthrin Exposure on Neurobehaviour, Hippocampal Tissue and Synaptic Plasticity in Wistar Rats.

This experiment was conducted to study the effects of Cyfluthrin (Cy) exposure on neurobehaviour, hippocampal tissue and synaptic plasticity in Wistar rats. First, it was found that high-dose Cy exposure could cause nerve injury, resulting in symptoms such as deficits in learning and memory ability, spatial exploration and autonomic motor function. Moreover, it was found that medium- and high-dose Cy exposure could cause an abnormal release of the neurotransmitter Glu. Second, brain tissue pathology showed that the middle and high doses of Cy caused tissue deformation, reduced the number of hippocampal puramidal cells, caused a disorder of these cells, decreased the number of Nissl bodies, and caused pyknosis of the hippocampal cell nuclear membrane and serious damage to organelles, indicating that exposure to these doses of Cy may cause hippocampal tissue damage in rats. Third, as the exposure dose increased, morphological changes in hippocampal synapses, including blurred synaptic spaces, a decreased number of synaptic vesicles and a decreased number of synapses, became more obvious. Moreover, the expression levels of the key synaptic proteins PSD-95 and SYP also decreased in a dose-dependent manner, indicating obvious synaptic damage. Finally, the study found that medium and high doses of Cy could upregulate the expression of A2AR in the hippocampus and that the expression levels of inflammatory factors and apoptosis-related proteins increased in a dose-dependent manner. Moreover, the expression of A2AR mRNA was correlated with neurobehavioural indicators and the levels of inflammatory factors, synaptic plasticity-related factors and apoptosis-related factors, suggesting that Cy may cause nerve damage in rats and that this effect is closely related to A2AR.

MESNA (2-Mercaptoethanesulfonate) Attenuates Brain, Heart, and Lung Injury Induced by Carotid Ischemia-Reperfusion in Rats.

Ischemia-reperfusion (I/R) causes organ dysfunction as a result of the increased formation of various reactive oxygen metabolites, infiltration of inflammatory cells, interstitial edema, cellular dysfunction, and tissue death. The study aimed to investigate the cytoprotective effect of 2-mercaptoethanesulfonate (MESNA) against tissue damage in rats exposed to carotid ischemia-reperfusion. Twenty-four male Wistar albino rats were divided into four groups (n = 6): sham, carotid I/R, I/R + MESNA (75 mg/kg), and I/R + MESNA (150 mg/kg) groups. To induce ischemia in rats, the carotid arteries were ligated with silk sutures for 10 min; the silk suture was then opened, and 1 h reperfusion was done. MESNA (75 and 150 mg/kg) was administered intraperitoneally 30 min before ischemia-reperfusion. Tissue samples from the animals were taken for histological examination, while the serum levels of some biochemical parameters were utilized to evaluate the systemic alterations. ANOVA and Tukey's post hoc tests were applied with a significance level of 5%. The ischemia-reperfusion-induced tissue damage as evidenced by increase in serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, lactate dehydrogenase, and matrix metalloproteinases (MMP-1, -2, -8) was significantly (P < 0.05-0.0001) reversed after treatment with MESNA in a dose-dependent manner. Treatment with MESNA (75 and 150 mg/kg), significantly (P < 0.05-0.0001) decreased the I/R-induced increase in serum tumor necrosis factor-alpha (TNF-α) and Interleukin-1-beta (IL-1 β). The results of this study suggest that MESNA has a protective effect on tissues by suppressing cellular responses to oxidants and inflammatory mediators associated with carotid ischemia-reperfusion.

Radioprotective Effects of Melatonin on Gamma Radiation- Induced Tissue Damage in Rats

&#x0D; &#x0D; Background &amp; Objective: Gamma rays are widely used in medicine despite their harmful effects on health. Our study evaluated the protective effects of melatonin on kidney, heart, and liver tissues.&#x0D; &#x0D; Materials &amp; Methods: Seventy-two adult male Wistar rats were categorized into nine groups. Groups 2 and 3 only received whole-body γ-ray irradiation (WBI) (2.0 Gy), no melatonin, interval time (IT) 8hr and 24hr. Groups 4 and 5 received WBI (8.0 Gy, no melatonin, 8hr and 24hr). Groups 6 and 7 received melatonin at 60 minutes (min) before WBI(2.0 Gy). Groups 8 and 9 received melatonin before WBI(8.0 Gy). All the rats were sacrificed 8 or 24 h after the experiments for laboratory and histopathological analysis. Serum levels of Blood Urea Nitrogen(BUN), Creatinine (Cr), Lactate dehydrogenase (LDH), Potassium (K), Gamma-glutamyl Transferase (GGT), Serum Glutamic-Oxaloacetic Transaminase(SGOT), Serum Glutamic-Pyruvic Transaminase(SGPT), Alkaline Phosphatase(ALP), c-reactive protein(CRP), Troponine(TPO) and histological features of liver, heart and kidney tissues were assessed. Statistical analysis was performed by One-Way ANOVA.&#x0D; &#x0D; Results: Our data did not indicate significant differences in BUN, Cr, K, and CRP between groups with or without melatonin treatment (P&gt;0.05); but differences were significant for LDH, GGT, SGOT, SGPT, ALP, and TPO (P&lt;0.05). The results showed that radiation-induced histopathological effects on the liver, heart, and kidneys were mitigated in the groups six to nine.&#x0D; &#x0D; Conclusion: The existence of significant differences in serum levels of LDH, GGT, SGOT, SGPT, ALP, and TPO in groups(6 to 9) and amelioration of the histopathological effects of irradiation on the liver, heart, and kidneys in the groups six to nine showed that the melatonin(100 mg/kg) is able to protect the body in gamma-radiation(2.0 Gy and 8.0 Gy).&#x0D; &#x0D;

(093) The Light-Controlled Nitric Oxide Donor “NORD-1” may Improve Erectile Function Without Hypotension and Tissue Damage in Rats With Neurogenic Erectile Dysfunction

Abstract Introduction Radical prostatectomy (RP) often causes erectile dysfunction (ED) because of cavernous nerve damage during surgery. This damage results in a decrease of nitric oxide (NO) in the penile corpus cavernosum. Therefore, NO supplementation is considered to be effective for post RP ED. However, NO has systemic side effects such as headache and hypotension. Recently, a red-light-controlled NO donor “NORD-1”, developed by our group, enables spatially and temporally controlled NO release by light irradiation. Our previous study reported that NORD-1 combined with red-light irradiation is effective for neurogenic ED model rats with bilateral cavernous nerve injury (BCNI). However, the side effects of the treatment have not yet been discussed. Objective The study aimed to investigate the potency of side effects associated with the combination of NORD-1 and red-light irradiation, using a ED rat model with BCNI. Methods In this study, eight-week-old male Wistar-ST rats were used. The rats were divided into four groups: Sham+SiR650 (control compound), Sham+NORD-1, BCNI+SiR650, and BCNI+NORD-1 (n=6). The sham or BCNI surgery was performed under anesthesia in each group. BCNI surgery was performed by crushing the cavernous nerves bilaterally. Four weeks post-surgery, erectile function before and after the injection of each reagent into the penile corpus cavernosum was evaluated based on the changes in intracavernous pressure (ICP) under electrostimulation of the cavernous nerve. After the administration of each reagent, the changes in ICP with and without light irradiation were also evaluated. ICP during electrostimulation was totally measured three times; once without reagent and light, once with reagent and without light and once with reagent and light. The variations in systemic arterial pressure during electrostimulation were also analyzed. After the experiment, penile samples were collected to observe NORD-1 localization using a fluorescence microscope. In addition, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to evaluate apoptosis in the corpus cavernousm. Results Before administering each reagent without light irradiation, the ICP/mean arterial pressure (MAP) ratios under stimulation in the BCNI+SiR650 and BCNI+NORD-1 groups were significantly lower than those in the Sham+SiR650 (P &amp;lt; 0.01) and Sham+NORD-1 (P &amp;lt; 0.05) groups. After administering each reagent without light irradiation, the ICP/MAP ratios in the BCNI+SiR650 and BCNI+NORD-1 groups remained significantly lower than those in the Sham+SiR650 and Sham+NORD-1 group (P &amp;lt; 0.05 and P &amp;lt; 0.01, respectively). After administering each reagent with light irradiation, the ICP/MAP ratios in the Sham+NORD-1 and BCNI+NORD-1 groups were significantly higher than those in the Sham+SiR650 (P &amp;lt; 0.01) and BCNI+NORD-1 (P &amp;lt; 0.01) groups, respectively. The changes of MAP during electrostimulation were not different under three different conditions in all four groups. Fluorescence of NORD-1 was detected only in corpus cavernousum which means it was not detected in urethra and dorsal vein of penis. Apoptosis was not detected in corpus cavernousum in all four groups. Conclusions The combination of NORD-1 and light irradiation is effective for neurogenic ED in rats with cavernous nerve injury. The treatment may not cause hypotension and tissue damage. Disclosure No

Fullerene C60 reduces acute lung injury by suppressing oxidative stress-mediated DMBA-induced apoptosis and autophagy by regulation of cytochrome-C/caspase-3/beclin-1/IL-1α/HO-1/p53 signaling pathways in rats

The objective of this study was to evaluate the effect of fullerene C60 nanoparticles against 7,12-dimethylbenz[a]anthracene (DMBA)-induced lung tissue damage in rats. 60 Wistar albino (8 weeks old) female rats were assigned into four groups: Control Group (C), Fullerene C60, DMBA, and Fullerene C60+DMBA. The rats in the DMBA and Fullerene C60+DMBA groups were administered DMBA (45 mg/kg bw, oral gavage). The rats in Fullerene C60, and Fullerene C60+DMBA groups were administered with Fullerene C60 (1.7 mg/kg bw, oral gavage). Expression levels of cytochrome-C, caspase-3, beclin-1, IL-1α, HO-1 and p53 proteins in lung tissue were determined by western blotting, lipid peroxidation malondialdehyde (MDA) analyzes, glutathione (GSH), glutathione peroxidase (GSH-Px), catalase activity (CAT) and total protein levels were determined by spectrophotometer. In addition, lung tissues were evaluated by histopathologically. Fullerene C60 reduced the increasing of MDA and IL-1α protein expression levels and attenuated histopathological changes in lung. Moreover, fullerene C60 enhanced the protein expression of cytochrome-C, caspase-3, beclin-1, HO-1, and p53, which were decreased in the DMBA group. Fullerene C60 has strong biological activity that it might be an effective approach for lung damage.

The effect of astaxanthin on amiodarone induced cardiac tissue damage in rat

Purpose: The aim of this study was to evaluate the effect of astaxanthin on amiodarone induced cardiac tissue damage.&#x0D; Materials and Methods: 3 groups were formed using 30 Wistar albino rats. In group 1 (control group) (n=10), neither any drugs were given nor anything was performed. In group 2 (amiodarone group) (n=10), 100 mg/kg amiodarone was given for 7 days. In group 3 (amiodarone+astaxanthin group) (n=10), 100 mg/kg amiodarone and 25 mg/kg astaxanthin were given for 7 days. Hearts were surgically extirpated in all groups. Blood malondialdehyde (MDA) levels and activities of catalase (CAT) and superoxide dismutase (SOD) were measured. Also, toxicity markers such as edema, hemorrhage, fibrosis, inflammatory cell infiltration were assessed by examining the slides prepared from cardiac tissue with microscopy.&#x0D; Results: The MDA levels were significantly higher and the activities of SOD, and CAT were lower in group 2 than group 3. Tissue damage was significantly higher in group 2 than group 3.&#x0D; Conclusion: According to our short term findings, astaxanthin reversed the toxicity of amiodarone on cardiac tissue. In the light of these promising results, we suggest that astaxanthin usage should be thought to protect the cardiac damage due to amiodarone.

The effect of coenzyme Q10 on oxidative stress parameters and testicular tissue damage in rats following monosodium glutamate induced excitatory intoxication

The effect of coenzyme Q10 on oxidative stress parameters and testicular tissue damage in rats following monosodium glutamate induced excitatory intoxication

Antioxidant and Pulmonary Protective Potential of Fraxinus xanthoxyloides Bark Extract against CCl4 -Induced Toxicity in Rats.

Fraxinus xanthoxyloides is a perennial shrub belonging to family Oleaceae, traditionally used for malaria, jaundice, pneumonia, inflammation, and rheumatism. Our study is aimed to assess the total phenolics (TPC), flavonoids (TFC), terpenoids contents (TTC) and antioxidant profiling of F. xanthoxyloides methanol bark extract (FXBM) and its fractions, hexane, chloroform, ethyl acetate and aqueous, along with high-performance liquid chromatography with diode-array detection (HPLC-DAD). Further, the antioxidant and pulmonary protective potential was explored against carbon tetrachloride (CCl4 )-induced CCl4-induced pulmonary tissue damage in rats. The highest TPC, TFC and TTC were found in FXBM (133.29±4.19 mg/g), ethyl acetate fraction (279.55±10.35 mg/g), and chloroform fraction (0.79±0.06 mg/g), respectively. The most potent antioxidant capacity was depicted by FXBM (29.21±2.40 μg/mg) and ethyl acetate fraction (91.16±5.51 μg/mg). The HPLC-DAD analysis revealed the predominance of gallic, chlorogenic, vanillic and ferulic acid in FXBM. The administration of CCl4 induced oxidative stress, suppressed antioxidant enzymes' activities including catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase. Further, it increased thiobarbituric acid reactive substances (TBARS) and H2 O2 levels, induced DNA injuries and reduced the total protein and glutathione content in lung tissues. The treatment of rats with FXBM restored these biochemical parameters to the normal level. Moreover, the histopathological studies of lung tissues demonstrated that FXBM protected rats' lung tissues from oxidative damage restoring normal lung functions. Thus, F. xanthoxyloides bark extract is recommended as adjuvant therapy as protective agent for patients with lung disorders.

Arginine attenuates chronic mountain sickness in rats via microRNA-144-5p.

Hypobaric hypoxia is an environmental stress leading to high-altitude pulmonary hypertension. While high-altitude pulmonary hypertension has been linked to high hematocrit findings (chronic mountain sickness; CMS). The present study is designed to investigate the effect of arginine (ARG) on hypobaric hypoxia-induced CMS of rats. Hypobaric hypoxia resulted in lower body weight, decreased appetite, increased pulmonary artery pressure, and deteriorated lung tissue damage in rats. Red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin values and blood viscosity were increased in rats, which were alleviated by ARG. microRNA (miRNA) microarray analysis was used to filter differentially expressed miRNAs after ARG in rats. miR-144-5p was reduced under hypobaric hypoxia and upregulated by ARG. miR-144-5p silencing aggravated the erythrocytosis and hyperviscosity in rats, and also accentuated tissue damage and excessive accumulation of RBC. The role of miR-144-5p in rats with CMS was achieved by blocking erythropoietin (EPO)/erythropoietin receptor (EPOR). In conclusion, ARG alleviated CMS symptoms in rodents exposed to hypobaric hypoxia by decreasing EPO/EPOR via miR-144-5p.