Protective effects of esculetin against doxorubicin-induced toxicity correlated with oxidative stress in rat liver: In vivo and in silico studies.

Doxorubicin (DOX) is widely used in cancer treatment but the dose-related toxicity of DOX on organs including the liver limit its use. Therefore, there is great interest in combining DOX with natural compounds with antioxidant properties to reduce toxicity and increase drug efficacy. Esculetin is a natural coumarin derivative with biological properties encompassing anti-inflammatory and antioxidant activities. In light of these properties, this study was meticulously crafted to investigate the potential of esculetin in preventing doxorubicin (DOX)-induced hepatotoxicity in Sprague-Dawley rats. The rats were divided into a total of six groups: control group, DOX group (administered DOX at a cumulative dose of 5 mg/kg intraperitoneally every other day for 2 weeks), E50 group (administered 50 mg/kg of esculetin intraperitoneally every day), E100 group (administered 100 mg/kg of esculetin intraperitoneally every day) and combined groups (DOX + E50 and DOX + E100) in which esculetin was administered together with DOX. The treatments, both with DOX alone and in combination with E50, manifested a reduction in catalase (CAT mRNA) levels in comparison to the control group. Notably, the enzymatic activities of superoxide dismutase (SOD), CAT, and glutathione peroxidase (GPx) witnessed significant decreases in the liver of rats treated with DOX. Moreover, DOX treatment induced a statistically significant elevation in malondialdehyde (MDA) levels, coupled with a concurrent decrease in glutathione (GSH) levels. Additionally, molecular docking studies were conducted. However, further studies are needed to confirm the hepatoprotective properties of esculetin and to precisely elucidate its mechanisms of action.

Biochemical and molecular assessment of oxidative stress in fruit fly exposed to azo dye Brilliant Black PN.

BACKGROUND: Azo dyes are widely used in the food industry to prevent color loss during processing and storage of products. This study aimed to investigate the effect of a diazo dye Brilliant Black PN (E151) on oxidative stress-related parameters in fruit flies (Drosophila melanogaster) at biochemical and molecular levels. METHODS AND RESULTS: Third instar larvae were transferred to a medium containing the dye at different doses (1, 2.5, and 5 mg/mL). Gene expression and activity of superoxide dismutase, catalase (CAT), glutathione peroxidase (GPX), and acetylcholinesterase (AChE) enzymes were determined in the heads of adult flies obtained from these larvae. In addition, the glutathione (GSH) and malondialdehyde levels were measured using spectrophotometric analysis. Mitochondrial DNA (mtDNA) copy number was also detected by real-time PCR. The results showed that treatment with 5 mg/mL of the dye caused a decrease in both gene expression and enzyme activity of CAT and GPx. Moreover, the same dose of dye treatment decreased AChE activity, GSH level, and mtDNA copy number. CONCLUSIONS: As a result, Brilliant Black PN dye can trigger toxicity by altering the level and activity of oxidative stress-related biomarkers in a dose-dependent manner. Therefore, more comprehensive studies are needed to elucidate the side effect mechanism and toxicity of this dye.

Effect of Ascorbic Acid on Oxidative Stress Parameters of Fruit Fly in the Presence of Fe (II).

Excessive iron intake causes lipid peroxidation and increases oxidative stress. Ascorbic acid is a natural compound with antioxidant and therapeutic properties. In this study, the effect of AA on oxidative stress parameters in fruit flies in the presence of iron was investigated. Third instar larvae were exposed to Fe and/or AA. Antioxidant enzyme activities, MDA, and GSH levels were determined in adult heads developing from the larvae. The mRNA levels of the enzymes were also analyzed. Iron treatment caused inhibition of SOD, CAT, and GPx enzymes, and only a decrease in the mRNA level of CAT. However, AA treatment together with iron prevented the inhibition. In addition, iron treatment increased the MDA level and decreased the GSH level. AA treatment together with iron ameliorated the changes in MDA and GSH levels. The results showed that AA can interfere with the iron-induced changes. Considering the potential of AA to ameliorate iron-induced changes, further studies are needed to elucidate the effect of AA on different mechanisms.

Tannic acid may ameliorate doxorubicin-induced changes in oxidative stress parameters in rat spleen.

Doxorubicin (DOX) is a potent and broad-spectrum drug widely used in the treatment of cancer. However, the toxicity and side effects of DOX on various organs limit its clinical use. Approaches using natural antioxidants with these drugs have the potential to alleviate negative side effects. The aim of this study was to investigate the potential protective effect of tannic acid, a polyphenolic compound found naturally in plants, against DOX-induced spleen toxicity. Expression levels of Alox5, Inos, IL-6, Tnf-α, Casp-3, Bax, SOD, GST, CAT and GPx genes were determined using cDNAs obtained from spleen tissues of rats treated with DOX, tannic acid and both. In addition, SOD, CAT, GPx and GST enzyme activities, and GSH and MDA levels were measured in tissues. In the spleen tissues, DOX caused a decrease in the level of GSH and an increase in the level of MDA. In addition, it was determined that DOX had a suppressive effect on CAT, GST, SOD and GPx mRNA levels and its enzyme activities, which are antioxidant system components. The mRNA expression levels of proinflammatory cytokine markers, apoptotic genes, and some factors involved in cell metabolism showed a change compared to the control after DOX application. However, as a result of tannic acid treatment with DOX, these changes approached the values of the control group. The findings showed that tannic acid had a protective effect on the changes in the oxidative stress and inflammation system in the rat spleen as a result of the application of tannic acid together with DOX.

Fluoride exposure causes behavioral, molecular and physiological changes in adult zebrafish (Danio rerio) and their offspring.

Fluoride exposure through drinking water, foods, cosmetics, and drugs causes genotoxic effects, oxidative damage, and impaired cognitive abilities. In our study, the effects of fluoride on anxiety caused by the circadian clock and circadian clock changes in a zebrafish model were investigated at the molecular level on parents and the next generations. For this purpose, adult zebrafish were exposed to 1.5 ppm, 5 ppm, and 100 ppm fluoride for 6 weeks. At the end of exposure, anxiety-like behaviors and sleep/wake behaviors of the parent fish were evaluated with the circadian rhythm test and the novel tank test. In addition, antioxidant enzyme activities and melatonin levels in brain tissues were measured. In addition, morphological, physiological, molecular and behavioral analyzes of offspring taken from zebrafish exposed to fluoride were performed. In addition, histopathological analyzes were made in the brain tissues of both adult zebrafish and offspring, and the damage caused by fluoride was determined. The levels of BMAL1, CLOCK, PER2, GNAT2, BDNF and CRH proteins were measured by immunohistochemical analysis and significant changes in their levels were determined in the F- treated groups. The data obtained as a result of behavioral and molecular analyzes showed that parental fluoride exposure disrupts the circadian rhythm, causes anxiety-like behaviors, and decreases the levels of brain antioxidant enzymes and melatonin in parents. In addition, delay in hatching, increase in death and body malformations, and decrease in blood flow velocity, and locomotor activity was observed in parallel with dose increase in offspring. On the other hand, an increase in offspring apoptosis rate, ROS level, and lipid accumulation was detected. As a result, negative effects of fluoride exposure on both parents and next generations have been identified.