Long-Term Risk of Reduced Cognitive Performance and Associated Factors in Discharged Older Adults with COVID-19: A Longitudinal Prospective Study.

BACKGROUND: Increasing numbers of reports have suggested a deterioration in cognitive performance after recovery from coronavirus disease 2019 (COVID-19), however insufficient information is available regarding long-term brain health and risk factors related to reduced cognitive performance in advanced age. We investigated the prevalence of reduced cognitive performance and its associated factors among older adults after COVID-19. METHODS: This prospective observational study enrolled older individuals (aged ≥65 years) hospitalized for COVID-19. Discharged patients were contacted after an average of 15 months and a brief battery was administered during telephone interviews to assess their mental status. RESULTS: Among the 174 patients, 77 (44.3%) showed reduced cognitive performance at follow-up. Multivariate analysis revealed that female sex, education level, and increased Deyo/Charlson Comorbidity Index score, which is an objective indicator of chronic disease burden, were independent risk factors for long-term cognitive performance. Depression and anxiety symptoms, assessed using the Patient Health Questionnaire-2 and Generalized Anxiety Disorder 2-item questionnaire at the end of the study, were not associated with reduced cognitive performance. CONCLUSION: Our findings provide key insights into discharged older adults with COVID-19 at risk of long-term cognitive impairment, and help to ascertain the factors associated with this problem.

Chlorogenic acid attenuates cisplatin-induced ovarian injury in rats.

The aim of this study was to determine the possible therapeutic effect of chlorogenic acid (CGA) on cisplatin (CDDP)-induced ovarian damage in rats. Rats were first exposed to CDDP (5 mg/kg) and then treated CGA (1.5 and 3 mg/kg) for three days. Oxidative stress (OS), inflammation and apoptosis markers were determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically. The levels of OS, inflammation and apoptosis biomarkers increased by CDDP administration (p < 0.05). Treatments with CGA significantly alleviated these markers dose-dependently (p < 0.05). These data reveal that CGA may exert an ovoprotective effect by reducing pro-inflammatory mediators and enhancing antioxidant status in ovarian tissue.

Syringic acid alleviates cisplatin-induced ovarian injury through modulating endoplasmic reticulum stress, inflammation and Nrf2 pathway.

BACKGROUND: Reproductive toxicity is one of the most important side effects of cisplatin (CIS) and leading to discontinuation of treatment. Syringic acid (SA) is a phenolic acid whose industrial use has increased in recent years due to its antioxidant properties. Recent reports highlight the importance of the supressed Nrf2 pathway in the molecular pathogenesis of CIS toxicity. Therefore, this study aimed to evaluate the therapeutic effect of SA on CIS-induced ovotoxicity through the Nrf2 pathway for the first time. MATERIAL AND METHODS: Thirty female rats were divided into 5 groups: control, CIS, CIS+SA (5 and 10 mg/kg) and only SA (per se, 10 mg/kg). CIS was administered intraperitoneally at a dose of 5 mg/kg on the 1st day, injections of SA followed by three consecutive days in the rats. Serum anti-mullerian hormone (AMH) levels and ovarian oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS), apoptosis and Nrf2 pathway markers were determined colorimetrically. Histopathological examinations of the ovaries with hematoxylin and eosin staining were also used to evaluate CIS-induced ovotoxicity. RESULTS: The CIS treatment depleted serum AMH levels, caused histopathological findings and increased OS, inflammation, ERS and apoptosis levels in ovarian tissue. However, treatments with SA significantly ameliorated CIS-induced biochemical and histopathological changes by activating Nrf2 pathway. CONCLUSION: The promising adjuvant potential of SA to alleviate CIS-related ovarian damage should be supported by more comprehensive studies.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

Alpha-pinene neutralizes cisplatin-induced reproductive toxicity in male rats through activation of Nrf2 pathway.

PURPOSE: Testicular toxicity is one of the most important side effects of cisplatin (CP) therapy. Alpha-pinene (AP) is a naturally occurring monoterpene with antioxidant character in plants. Here, we aimed to evaluate the therapeutic activity of AP against CP-induced testicular toxicity by including the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway in rats. METHODS: Thirty male rats were divided into 5 groups: control, CP, CP + AP (5 and 10 mg/kg) and only AP (10 mg/kg). CP was administered intraperitoneally at a dose of 5 mg/kg on the first day, followed by three consecutive injections of AP. Serum reproductive hormone levels were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in testicular tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of AP on this situation were also addressed. RESULTS: Treatment with CP significantly increased OS, inflammation, ERS and apoptosis in testicular tissue. Administrations of AP resulted in an amelioration of these altered parameters. The mechanism of therapeutic effect of AP appeared to involve induction of Nrf2. Furthermore, these results were also confirmed by histological data. CONCLUSION: Results suggest that AP can exhibit therapeutic effects against CP-induced testicular toxicity. It can be concluded that AP may be a potential molecule to abolish reproductive toxicity after chemotherapy.

Evaluation of the therapeutic effects of arbutin on cisplatin-induced ovarian toxicity in rats through endoplasmic reticulum stress and Nrf2 pathway.

Arbutin (ARB) is a glycosylated hydroquinone with potent antioxidant effects. Although cisplatin (CP) is widely used in chemotherapy, its toxicity in healthy tissues, including ovotoxicity, is an insurmountable problem. This study aimed to evaluate the therapeutic effect of ARB against CP-related ovototoxicity by including nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in rats for the first time. Rats treated one dose of CP (5 mg/kg) on the first day, followed by ARB (5 and 10 mg/kg) for three days. Serum reproductive hormone levels were determined using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers in ovarian tissue were also determined colorimetrically. In addition, how CP affects Nrf2 pathway and the effect of ARB on this situation were also addressed. ARB treatment reduced the levels of markers of OS, inflammation, ERS and apoptosis in ovarian tissue of CP-stimulated animals. ARB regenerated the depleted antioxidant system by triggering Nrf2 pathway in the ovarian tissues of animals stimulated by CP. Histological findings also supported the therapeutic efficacy of ARB. The results indicate that ARB may have therapeutic effects against CP-induced reproductive toxicity with its Nrf2 activator potential. ARB should be tested in more extensive studies as a new generation chemopreventive candidate molecule.

Gentisic acid ameliorates cisplatin-induced reprotoxicity through suppressing endoplasmic reticulum stress and upregulating Nrf2 pathway.

Reproductive toxicity is a serious side effect of cisplatin (CP) chemotherapy. Gentisic acid (GTA) is a phenolic acid with strong antioxidant properties. Here, we aimed to determine therapeutic effect of GTA against CP-induced testicular toxicity in rats for the first time. Male Sprague-Dawley rats received a single dose of CP (5 mg/kg; intraperitoneal) and treated with GTA (1.5 and 3 mg/kg; intraperitoneal; 3 consecutive days). The levels of oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis biomarkers were assessed in the testicular tissue of rats. In addition, how CP affects the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway and the effect of GTA on this situation were also addressed in the testicular tissue. CP administration induced histopathological changes in testicular tissue of rats with a significant increase in OS, inflammation, ERS and apoptosis biomarkers and a decrease in antioxidant capacity and Nrf2 expression levels. Administrations of GTA resulted in an amelioration of these altered parameters. These data suggest that GTA may be a potential therapeutic agent against CP-induced testicular toxicity. Activation of the Nrf2 pathway plays a key role of this therapeutic effect of GTA.

Phenotypic Investigation of Virulence Factors, Susceptibility to Ceragenins, and the Impact of Biofilm Formation on Drug Efficacy in Candida auris Isolates from Türkiye.

Candida auris has emerged as a significant fungal threat due to its rapid worldwide spread since its first appearance, along with its potential for antimicrobial resistance and virulence properties. This study was designed to examine virulence characteristics, the efficacy of ceragenins, and biofilm-derived drug resistance in seven C. auris strains isolated from Turkish intensive care patients. It was observed that none of the tested strains exhibited proteinase or hemolysis activity; however, they demonstrated weak phospholipase and esterase activity. In addition, all strains were identified as having moderate to strong biofilm formation characteristics. Upon determining the minimum inhibitory concentrations (MIC) of ceragenins, it was discovered that CSA-138 exhibited the highest effectiveness with a MIC range of 1-0.5 µg/mL, followed by CSA-131 with a MIC of 1 µg/mL. Also, antimicrobial agents destroyed mature biofilms at high concentrations (40-1280 µg/mL). The investigation revealed that the strains isolated from Türkiye displayed weak exoenzyme activities. Notably, the ceragenins exhibited effectiveness against these strains, suggesting their potential as a viable treatment option.

Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress / El propóleo mejora el daño testicular inducido por isquemia/reperfusión al reducir el estrés oxidativo

Purpose: This study was performed to evaluate the effect of ethanolic extract of Turkish propolis (EEP) on testicular ischemia/reperfusion (I/R) damage in rats in terms of biochemistry and histopathology, for the first time. Methods: A total of 18 male Sprague-Dawley rats were divided into three groups with six rats in each group: control, torsion/detorsion (T/D), and T/D+EEP (100mg/kg). Testicular torsion was performed by 720° rotating the left testicle in a clockwise direction. The duration of ischemia was 4h and orchiectomy was performed after 2h of detorsion. EEP was applied only once 30min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods. Oxidative stress index (OSI) was calculated by proportioning tissue TOS and TAS values to each other. Tissue glutathione (GSH) and glutathione peroxidase (GPx) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. Results: In the T/D group, it was determined that statistically significant decreasing in TAS, GSH, GPx levels and Johnsen score, and increasing in TOS, OSI and MDA levels (p<0.05) compared with control group. EEP administration statistically significantly restored this I/R damage (p<0.05). Conclusion: This is the first study to show that propolis prevent I/R-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms. (AU)

Objetivo: Este estudio se realizó para evaluar por primera vez el efecto del extracto etanólico de propóleo turco (EEP) sobre el daño por isquemia/reperfusión (I/R) testicular en ratas en términos de bioquímica e histopatología. Métodos: Un total de 18 ratas macho Sprague-Dawley se dividieron en 3 grupos con 6 ratas en cada grupo: control, torsión/detorsión (T/D) y T/D+EEP (100mg/kg). La torsión testicular se realizó con una rotación de 720° del testículo izquierdo en el sentido de las agujas del reloj. La duración de la isquemia fue de 4h y la orquiectomía se realizó a las 2h de la detorsión. EEP se aplicó solo una vez 30min antes de la detorsión. Los niveles de malondialdehído tisular (MDA), estado oxidante total (TOS) y estado antioxidante total (TAS) se determinaron mediante métodos colorimétricos. El índice de estrés oxidativo (OSI) se calculó proporcionando los valores de TOS y TAS del tejido entre sí. Los niveles de glutatión tisular (GSH) y glutatión peroxidasa (GPx) se determinaron utilizando kits de ensayo inmunoabsorbente ligado a enzimas (ELISA). Se utilizó el sistema de puntuación de testículos de Johnsen para la evaluación histológica. Resultados: En el grupo T/D, se determina una disminución estadísticamente significativa en los niveles de TAS, GSH, GPx y puntuación de Johnsen y un aumento en los niveles de TOS, OSI y MDA (p<0,05) en comparación con el grupo control. La administración de EEP restauró de forma estadísticamente significativa este daño I/R (p<0,05). Conclusión: Este es el primer estudio que demuestra que el propóleo previene el daño testicular inducido por I/R a través de su actividad antioxidante. Se necesitan estudios más completos para ver los mecanismos subyacentes. (AU)

Efficacy of Ceragenins Alone and in Combinations with Antibiotics Against Multidrug-Resistant Gram Negative Pathogens from Bloodstream Infections.

Ceragenins (CSAs) that mimic the activities of antimicrobial peptides may be new options for the treatment of infections caused by multidrug-resistant pathogens. This study investigated the antibacterial activities of eight different ceragenins against MDR pathogens and the synergistic effects of some ceragenins in combinations with antibiotics (meropenem-MEM, ceftazidime + avibactam-CZA, tigecycline-TIG). A disc diffusion method was used for antibiotic susceptibility tests, a broth microdilution, and checkerboard methods were used to detect minimum inhibitory concentrations (MICs) and the effects of combinations, respectively. While MIC90 values CSA-13, CSA-44, CSA-131 against Klebsiella pneumoniae isolates had similar effect with MEM (8 µg/ml); CSA-13, CSA-44, CSA-131, CSA-138, and CSA-144 had better activity than MEM against Acinetobacter baumannii and Pseudomonas aeruginosa isolates. In particular, CSA-44 and CSA-131 were effective against A. baumannii and P. aeruginosa isolates which resistant to both COL and MEM. CSA-44+MEM and CSA-131+CZA combinations showed synergistic activity against most (70%) of MDR- E. coli isolates. Although TIG is known to have weak activity in nonfermentative bacteria, CSA-44+TIG combination showed synergistic activity against two (17%) of the A. baumanni isolates. In addition, CSA-44+TIG and CSA-131+TIG combinations showed additive effects against all P. aeruginosa isolates. Antagonism was not detected in any of the combinations. CSA-44 and CSA-131 alone/or in combinations with MEM or CZA can be considered as new alternative treatments in serious infections caused by MDR pathogens.

Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway.

Although cisplatin (CDDP) is an effective anticancer agent, the ovotoxicity that can occur in female patients limits its use. Oxidative stress (OS) and inflammation are known to contribute to CDDP-induced ovotoxicity. Vanillic acid (VA) is a dietary herbal secondary metabolite with high free radical scavenging activity. It was aimed to evaluate the therapeutic effects of VA against CDDP-induced ovotoxicity in rats in this study for the first time. Ovotoxicity was achieved with a single dose of CDDP (5 mg/kg) in female rats. The therapeutic effect of VA was evaluated with 3-day administration of two different doses (5 and 10 mg/kg). While OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were measured in tissue samples, the levels of reproductive hormones were determined in serum samples using colorimetric methods. The results showed that CDDP-induced nuclear factor erythroid 2-associated factor 2 (Nrf2) inhibition combined with increased OS, inflammation, ERS and apoptosis increased ovarian damage. VA treatments reversed these changes via activating Nrf2 pathway dose-dependently. In addition, histopathological findings also supported the biochemical results. VA may be a good therapeutic molecule candidate for CDDP-induced ovarian damage due to strong antioxidant and Nrf2 activator properties.

Propolis ameliorates ischemia/reperfusion-induced testicular damage by reducing oxidative stress.

PURPOSE: This study was performed to evaluate the effect of ethanolic extract of Turkish propolis (EEP) on testicular ischemia/reperfusion (I/R) damage in rats in terms of biochemistry and histopathology, for the first time. METHODS: A total of 18 male Sprague-Dawley rats were divided into three groups with six rats in each group: control, torsion/detorsion (T/D), and T/D+EEP (100mg/kg). Testicular torsion was performed by 720° rotating the left testicle in a clockwise direction. The duration of ischemia was 4h and orchiectomy was performed after 2h of detorsion. EEP was applied only once 30min before detorsion. Tissue malondialdehyde (MDA), total oxidant status (TOS) and total antioxidant status (TAS) levels were determined using colorimetric methods. Oxidative stress index (OSI) was calculated by proportioning tissue TOS and TAS values to each other. Tissue glutathione (GSH) and glutathione peroxidase (GPx) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: In the T/D group, it was determined that statistically significant decreasing in TAS, GSH, GPx levels and Johnsen score, and increasing in TOS, OSI and MDA levels (p<0.05) compared with control group. EEP administration statistically significantly restored this I/R damage (p<0.05). CONCLUSION: This is the first study to show that propolis prevent I/R-induced testicular damage through its antioxidant activity. More comprehensive studies are needed to see the underlying mechanisms.

The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats.

5-Fluorouracil (5-FU) is a fluoropyrimidine group antineoplastic drug with antimetabolite properties and ovotoxicity is one of the most important side effects. Silibinin (SLB) is a natural compound that is used worldwide and stands out with its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the therapeutic effect of SLB in 5-FU-induced ovototoxicity using biochemical and histological analysis. This study was carried out in five main groups containing six rats in each group: control, SLB (5 mg/kg), 5-FU (100 mg/kg), 5-FU + SLB (2.5 mg/kg), and 5-FU + SLB (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and caspase-3 were determined using spectrophotometric methods. Hematoxylin and eosin staining method was employed for histopathological examination. MDA, TOS, 8-OHdG, TNF-α, MPO, and caspase-3 levels in 5-FU group were significantly increased compared with the control group, while the levels of TAS, SOD, and CAT were decreased (p < 0.05). SLB treatments statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the 5-FU group compared with the control group, SLB treatments also statistically significantly restored these damages (p < 0.05). In conclusion, SLB has a therapeutic effect on the ovarian damage induced by 5-FU via decreasing the levels of oxidative stress, inflammation, and apoptosis. It may be helpful to consider the usefulness of SLB as an adjuvant therapy to counteract the side effects of chemotherapy.

Antibacterial and Antibiofilm Activities of Ceragenins Alone and in Combination with Levofloxacin Against Multidrug Resistant Myroides spp. Clinical Isolates from Patients with Urinary Tract Infections.

Myroides spp. are rare opportunistic pathogens, but they can be life-threatening because of their multidrug-resistant drug properties and their potential to cause outbreaks, especially in immunosuppressed patients. In this study, 33 isolates isolated from intensive care patients with urinary tract infections were examined for drug susceptibility. All isolates except three proved to be resistant to the tested conventional antibiotics. The effects of ceragenins, a class of compounds developed to mimic endogenous antimicrobial peptides, were evaluated against these organisms. The MIC values of nine ceragenins were determined, and the most effective ceragenins were CSA-131 and CSA-138. Three isolates that were susceptible to levofloxacin and two isolates resistant to all antibiotics underwent 16 s rDNA analysis, and whereas resistant isolates were identified as M. odoratus, susceptible isolates were identified as M. odoratimimus. CSA-131 and CSA-138 showed rapid antimicrobial effects observed in time-kill analyses. Combinations of ceragenins and levofloxacin caused a significant increase in antimicrobial and antibiofilm activities against M. odoratimimus isolates. In this study, Myroides spp. were found to be multidrug-resistant and have biofilm forming capacity, and ceragenins CSA-131 and CSA-138 were found to be especially effective on both planktonic and biofilm forms of Myroides spp.

Arbutin abrogates testicular ischemia/reperfusion injury in rats through repression of inflammation and ER stress.

The aim of this study was to investigate the effects of arbutin (ARB) administration on oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis in an experimental testicular torsion/detorsion (T/D)-induced testicular injury model for the first time. A total of 24 male Sprague-Dawley rats were divided into four groups with six rats in each group: sham control, T/D, T/D+ARB (50 mg/kg) and T/D+ARB (100 mg/kg). Torsion and detorsion times were applied as 4 h and 2 h, respectively. The levels of lipid peroxidation [malondialdehyde (MDA)] and oxidative stress [total oxidant status (TOS) and total antioxidant status (TAS)] in testicular tissues were determined using colorimetric methods. The levels of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], antioxidant system [superoxide dismutase (SOD) and catalase (CAT)], pro-inflammatory cytokines [high mobility group box 1 (HMGB1), nuclear factor kappa B protein 65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO)], ER stress [78-kDa glucose-regulated protein (GRP78), activating transcription factor 6 (ATF6) and CCAAT-enhancer-binding protein homologous protein (CHOP)] and apoptosis (caspase-3) markers in testicular tissues were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In the T/D group, it was determined that statistically significant increasing in the levels of oxidative stress, inflammation, ER stress and apoptosis compared with sham control group (p < 0.05). ARB administrations statistically significantly restored testicular I/R damage in a dose dependent manner (p < 0.05). In addition, it was determined that the data of histological examinations supported the biochemical results. Our findings support the hypothesis that ARB may be used as a protective agent against T/D-induced testicular damage.

Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

PURPOSE: To investigate the possible protective role of syringic acid on torsion/detorsion-induced testicular injury using biochemical and histopathological approaches for the first time. METHODS: A total of 24 rats were divided into 4 groups: sham control, torsion/detorsion, torsion/detorsion + syringic acid (50 mg/kg and 100 mg/kg). Tissue malondialdehyde, total oxidant status and total antioxidant status levels were determined using colorimetric methods. Tissue 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1, nuclear factor kappa B protein 65, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor-6, C/EBP homologous protein and caspase-3 levels were determined using commercial enzyme-linked immunosorbent assay kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: Compared with the control group, the levels of oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis were significantly increased in the torsion/detorsion group (p < 0.05). Syringic acid administrations statistically significantly restored these damage in a dose dependent manner (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. CONCLUSION: The overall results suggest that syringic acid emerges as a potential compound for the treatment of testicular torsion and may be subject to clinical trials.

Ameliorative effect of gallic acid on cisplatin-induced ovarian toxicity in rats.

The aim of the present study was to evaluate the protective effect of gallic acid (GA) against cisplatin (CDDP)-induced ovarian toxicity, for the first time. The ovarian damage was generated with CDDP (5 mg/kg) intraperitoneally (i.p.) administration in rats. GA (2.5 and 5 mg/kg) were administered i.p. for 3 consecutive days. The study was carried out in 5 main groups containing 6 rats in each group: control, GA (5 mg/kg), CDDP, CDDP + GA (2.5 mg/kg) and CDDP + GA (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3 and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3 and TNF-α (p < 0.05) compared with control group. GA administrations statistically significantly restored this damage (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration and leukocyte infiltration were significantly higher in the CDDP group than in the control group, GA administrations statistically significantly restored these damages (p < 0.05). In conclusion, this study showed that GA prevented CDDP-induced ovarian damage with its antioxidant, anti-apoptotic and anti-inflammatory activities. More comprehensive studies are needed to see the underlying mechanisms.

Nigella sativa oil reduces oxidative/nitrosative stress in the salivary gland of rats exposed to total cranial irradiation.

Patients with head and neck cancer who receive radiotherapy experience serious side-effects during and after their treatment. Radiotherapy affects the salivary glands, causing a change in the composition of the saliva and a decrease in its flow. In this study, we aimed to investigate whether Nigella sativa oil (NSO) has a possible protective effect in preventing the harmful effects of free radicals formed by radiotherapy in rats. Thirty-six male Wistar-Albino rats weighing 200 ± 20 g were used. The rats were randomly divided into four groups: control, sham, irradiation (IR), and IR plus NSO groups. Xanthine oxidase (XO), nitric oxide synthase (NOS) activities, nitric oxide (NO•), peroxynitrite (ONOO-), malondialdehyde (MDA) levels were determined in salivary tissue of rats. NOS, XO activities, NO•, ONOO-, and MDA values were found to be significantly higher in the irradiated rats only compared to all other groups. As a results, NSO reduces oxidative/nitrosative stress markers and has antioxidant effects, which also augments the antioxidant capacity in the salivary tissue of rats.

Suppression of cisplatin-induced ovarian injury in rats by chrysin: an experimental study.

The aim of this study was to investigate the potential therapeutic efficacy of chrysin (CHS) against ovotoxicity caused by intraperitoneal administration of cisplatin (CDDP) in rats. In this experimental study, 24 female rats were randomly divided into four groups: control, CHS (2 mg/kg), CDDP (5 mg/kg) and CDDP (5 mg/kg) + CHS (2 mg/kg). The levels of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), interleukin-6 (IL-6) and myeloperoxidase (MPO) were determined in the ovarian tissues using spectrophotometric methods. In addition, the ovarian samples were evaluated histopathologically by hematoxylin&eosin staining. The results revealed that the levels of MDA, TOS, IL-6 and MPO significantly increased by CDDP administration compared with control group (p < 0.05). Also, it was found that CDDP significantly decreased TAS and SOD levels (p < 0.05). CHS ameliorated CDDP-induced the increased levels of MDA, TOS, IL-6, MPO and increased the levels of TAS and SOD significantly (p < 0.05). Histological findings also supported the therapeutic effect of CHS against CDDP-induced ovarian damage parameters. In conclusion, our results showed that CHS exhibits a therapeutic effect against CDDP-induced ovotoxicity and therefore the use of CHS after chemotherapy may improve the side effets of CDDP. IMPACT STATEMENTWhat is already known about this subject? Cisplatin (CDDP) is an effective and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited due to dose-related tissue toxicity. Chrysin (CHS), a natural flavone, exhibits various beneficial activities, including antioxidant, anti-inflammatory and anticancer. There are increasing evidences in the literature that CHS reduces the toxicity of various chemotherapeutic agents, such as CDDP, doxorubicin and cyclophosphamide, in colon, kidney and liver tissues through its antioxidant and anti-inflammatory potential.What do the results of this study add? This study demonstrated that CHS can abolish CDDP-induced in vivo ovarian injury by decreasing MDA, TOS, IL-6 and MPO levels and increasing SOD and TAS levels through its antioxidant and anti-inflammatory potential.What are the implications of these findings for clinical practice and/or further research? This study revealed the therapeutic potential of CHS against CDDP-induced acute ovotoxicity, for the first time. Further pre-clinical studies are necessary to prove the beneficial effect of CHS on the prevention of CDDP-induced ovarian toxicity.

In vitro activity of ceragenins against Burkholderia cepacia complex.

Burkholderia cepacia complex (Bcc) species are aerobic, Gram-negative and non-fermantative bacilli. Bcc can cause clinical symptoms in patients with cystic fibrosis, ranging from asymptomatic carriage to fatal pneumonia. A pressing need exists for new antimicrobial agents that target Bcc. Ceragenins, CSA-13, CSA-131 and CSA-131 with 5% Pluronic® F127 (CSA-131P), were evaluated against Bcc clinical isolates (n = 42). MICs of ceragenins and conventional antibiotics were determined. Time-kill curve experiments were performed with 1x, 4x MICs of ceragenins and sulfamethoxazole-trimethoprim (SXT), levofloxacin. MIC50/ MIC90 results (mg l-1) of CSA-13, CSA-131 and CSA-131P were determined as 16/64, 16/128 and 16/128, respectively. CSA-13 and CSA-131 showed bactericidal activity. CSA-13 - levofloxacin combination displayed synergistic activity against Bcc. First-generation (CSA-13) and second-generation (CSA-131 and CSA-131P) ceragenins have significant antimicrobial effects on Bcc. The findings of this study demonstrate that combinations of ceragenins with currently marketed antibiotics could be synergistic in vitro against Bcc isolates. These results suggest that combination therapy with conventional antibiotics could be an alternative approach for treating Bcc infections in the future.