Effects of sinapic acid on lead acetate-induced oxidative stress, apoptosis and inflammation in testicular tissue

In this study, the effect of lead acetate (PbAc) and sinapic acid (SNP) administration on oxidative stress, apoptosis, inflammation, sperm quality and histopathology in testicular tissue of rats was tried to be determined. PbAc was administered at a dose of 30 mg/kg/bw for 7 days to induce testicular toxicity in rats. Oral doses of 5 and 10 mg/kg/bw SNP were administered to rats for 7 days after PbAc administration. According to our findings, while PbAc administration increased MDA content in rats, it decreased GPx, SOD, CAT activity and GSH content. NF-kB, IL-1β, TNF-α, and COX-2, which are among the inflammation parameters that increased due to PbAc, decreased with the administration of SNP. Nrf2, HO-1, and NQO1 mRNA transcript levels decreased with PbAc, but SNP treatments increased these mRNA levels in a dose-dependent manner. RAGE and NLRP3 gene expression were upregulated in PbAc treated rats. MAPK14, MAPK15, and JNK relative mRNA levels decreased with SNP treatment in PbAc treated rats. While the levels of apoptosis markers Bax, Caspase-3, and Apaf-1 increased in rats treated with PbAc, the level of Bcl-2 decreased, but SNP inhibited this apoptosis markers. PbAc caused histopathological deterioration in testis tissue and negatively affected spermatogenesis. When the sperm quality was examined, the decrease in sperm motility and spermatozoon density caused by PbAc, and the increase in the ratio of dead and abnormal spermatozoa were inhibited by SNP. As a result, while PbAc increased apoptosis and inflammation by inducing oxidative stress in testicles, SNP treatment inhibited these changes and increased sperm quality

Effects of chrysin against isoniazid-induced lung injury in rats

Bu çalışmanın amacı; tüberküloz tedavisinde yaygın olarak kullanılan izoniazid (İZN) kaynaklı akciğer hasarına karşı doğal flavonoidlerden olan krisin (KRS)’in etkilerinin araştırılmasıdır. Çalışmada Spraque Dawley cinsi 35 adet erkek rat rastgele 5 gruba ayrıldı: Kontrol grubu, İZN uygulanan grup, KRS 50 mg/kg uygulanan grup, İZN+ KRS 25 mg/kg uygulanan grup ve İZN+ KRS 50 mg/kg uygulanan grup. İZN’nin glutatyon peroksidaz (GPx), süperoksit dismutaz (SOD) ve katalaz (KAT) gibi antioksidan enzim aktivitelerini ve glutatyon (GSH) düzeylerini azaltıp, lipid peroksidasyonunu (LPO) artırarak oksidatif hasara neden olduğu belirlendi. Ayrıca İZN ile kombine uygulanan KRS uygulamasının GSH seviyesini ve antioksidan enzim aktivitelerini artırdığı, lipid peroksidasyonunu ise azalttığı ettiği tespit edildi. Çalışmada incelenen nükleer faktör eritroid 2 ile ilişkili faktör 2 (Nrf-2) ve hem oksijenaz-1 (HO-1) seviyelerinin İZN grubunda gen ekspresyonu düzeyinde, nükleer faktör kappa B (NF-κB) ekspresyonunu ise immunhistokimyasal incelemede arttığı tespit edilmiş, buna karşın KRS uygulamasının bu belirteçlerin düzeylerinde azalmaya neden olduğu gözlenmiştir. Birlikte ele alındığında, bu sonuçlar KRS'in oksidan-antioksidan dengesini koruyarak ve NF-κB, Nrf-2 ve HO-1 ekspresyonlarını azaltarak İZN’nin neden olduğu akciğer toksisitesinde faydalı etkilere sahip olduğunu düşündürmektedir.The aim of the study was to investigate the effects of chrysin (CH), one of the natural flavonoids, against isoniazid lung damage caused by isoniazid (INH), which was widely used in the treatment of tuberculosis. Male Sprague-Dawley rats were randomly divided into five groups: a control group, INH-treated group, CH alone treated group 50 mg / kg, INH + CH 25 mg / kg treated group, and INH+ CH 50 mg / kg treated group. It was determined that INH caused oxidative damage by decreasing antioxidant enzyme activities such as glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) and increasing lipid peroxidation (LPO). In addition, it was found that the administration of CH to INH-treated rats increased GSH level and antioxidant enzyme activities, and decreased lipid peroxidation. It was observed that the nuclear factor erythroid 2 related factor 2 (Nrf-2) and oxygenase-1 (HO-1) expression levels were up-regulated in the INH-treated group, and the expression of NF-κB increased in the INH-treated group in the immunohistochemical examination, and the CH administration, on the other hand, decreased the levels of these markers. Taken together, these results suggested that CH had beneficial effects in INH-induced lung toxicity by maintaining the oxidant-antioxidant balance and decreasing NF-κB, Nrf-2, and HO-1 expressions

Protective effects of zingerone against sodium arsenite-induced lung toxicity: A multi-biomarker approach

Objective(s): Sodium arsenite (SA) exposure is toxic to the body. Zingerone (ZNG) is a flavonoid with many biological properties found naturally in honey and plants. This study aimed to determine the effects of ZNG on SA-induced rat lung toxicity.Materials and Methods: Thirty-five male Sprague rats were divided into Control, SA, ZNG, SA+ZNG25, and SA+ZNG50 groups (n=7). SA 10 mg/kg and ZNG were administered at two doses (25 and 50 mg/kg) (orally, 14 days). Analysis of oxidative stress, inflammation damage, apoptosis damage, and autophagic damage markers in lung tissue were determined by biochemical and histological methods. Results: The administration of ZNG reduced oxidative stress by increasing SA-induced decreased antioxidant enzyme activities, increasing Nrf-2, HO-1, and NQO1, and decreasing MDA level. ZNG administration reduced inflammation marker levels. Anti-apoptotic Bcl-2 increased and apoptotic Bax and Caspase-3 decreased with ZNG. ZNG promoted the regression of autophagy by reducing Beclin-1, LC3A, and LC3B levels.Conclusion: Evaluating all data showed that SA caused toxic damage to lung tissue by increasing inflammation, apoptosis, autophagy, and oxidant levels, whereas ZNG had a protective effect by reducing this damage

Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes

Arsenic is widely available in the environment and arsenic toxicity is a public health problem of serious concern worldwide. Zingerone is a promising phytochemical with various pharmacological effects. In this study, the potential protective effect of zingerone against sodium arsenite (NaAsO2, SA) induced nephrotoxicity was investigated. Thirty-five male Sprague-Dawley rats were divided into five different groups as control, zingerone, SA, SA + zingerone 25, SA + zingerone 50. SA was administered alone at a dose of 10 mg/kg for 14 days or given 30 min before zingerone (25 mg/kg or 50 mg/kg) treatment. At the end of the experiment, the kidney tissues was examined biochemically, molecularly and microscopically. SA toxicity was associated with increased malondialdehyde level, whereas glutathione, superoxide dismutase, catalase, and glutathione peroxidase were decreased. Administration of SA caused inflammation in the kidney tissue by upregulation of NF-κB and IL-1β, TNF-α, IL-6, iNOS, COX-2, MAPK14, MAPK15, JNK. SA administration caused apoptosis in the kidney by upregulating caspase-3 and Bax levels and downregulating Bcl-2, and autophagy by activating beclin-1. Also, SA administration showed a suppressive effect on AKT2 and FOXO1 mRNA transcript levels. All these factors impair kidney function and increase creatinine and urea levels, resulting in pathological changes and a decrease in nephrin. Treatment with zingerone at doses of 25 and 50 mg/kg significantly reduced oxidative stress, inflammation, apoptosis and autophagy in kidney tissue. In addition, it was confirmed by histological evaluation as well as serum urea and creatinine levels that kidney damage due to SA toxicity can be modulated by zingerone administration

Beneficial effects of quercetin on vincristine-induced liver injury in rats: Modulating the levels of Nrf2/HO-1, NF-kB/STAT3, and SIRT1/PGC-1α

Our experimental objective was to investigate the hepatotoxic effect of vincristine (VCR) administration in rats and determined whether combined therapy with Quercetin (Quer) ensured protection. Five groups with seven rats each were used for this purpose, and experimental groups were formulated as follows: Control group; Quer group; VCR group; VCR plus Quer 25 group; VCR plus Quer 50 group. The results showed that VCR significantly increased the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes. Besides, VCR caused considerable increases in the malondialdehyde (MDA) contents, along with significant decreases in reduced glutathione levels, superoxide dismutase, catalase, and glutathione peroxidase enzyme activities in the rat livers. Quer treatment in VCR toxicity markedly decreased the activity of ALT, AST, ALP enzymes, and MDA contents and enhanced the activities of antioxidant enzymes. The results also showed that VCR significantly increased the levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3 and decreased the expression of Bcl2 and levels of Nrf2, HO-1, SIRT1, and PGC-1α. Compared to the VCR group, Quer treatment exhibited significantly lower levels of NF-kB, STAT3, and the expression of caspase 3, Bax, and MAP LC3, and higher levels of Nrf2, HO-1, SIRT1, and PGC-1α. In conclusion, our study demonstrated that Quer could alleviate the harmful effects of VCR via activation of NRf2/HO-1 and SIRT1/PGC-1α pathways, and via attenuation of oxidative stress, apoptosis, autophagy, and NF-kB/STAT3 pathways

Protective effects of sinapic acid against lead acetate-induced nephrotoxicity: a multi-biomarker approach

Lead acetate (PbAc) is one of the top five most dangerous toxic heavy metals, particularly leading to kidney damage and posing serious health risks in both humans and animals. Sinapic acid (SNP) is a naturally occurring flavonoid found in fruits and vegetables that stands out with its antioxidant, anti-inflammatory, and anticancer properties. This is the first study to investigate the effects of SNP on oxidative stress, inflammation, apoptosis, autophagy and endoplasmic reticulum (ER) stress in PbAc-induced nephrotoxicity in rats by biochemical, molecular and histological methods. 35 Spraque dawley rats were randomly divided into five groups of 7 rats each: control, PbAc, SNP (10mg/kg), PbAc + SNP 5, PbAC + SNP 10. PbAc at a dose of 30 mg/kg body weight was administered via oral gavage alone or in combination with SNP (5 and 10 mg/kg body weight) via oral gavage for seven days. While PbAc impaired renal function by increasing serum urea and creatinine levels, SNP decreased these levels and contributed to the improvement in renal function. The administration of SNP reduced oxidative stress by increasing PbAc-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels, decreasing MDA levels, a marker of increased lipid peroxidation. SNP administration reduced NF-κB, TNF-α, IL-1β, NLRP3, and RAGE mRNA transcription levels, NF-κB, and TNF-α protein levels that are among the PbAc-induced increased inflammation parameters. Decreases in antiapoptotic Bcl-2 and increases in apoptotic Bax, APAF-1, and Caspase-3 due to PbAc exposure, SNP reversed the situation. SNP reduced ER stress caused by PbAc by increasing PERK, IRE1, ATF-6, CHOP, and GRP-78 levels and made it tend to regress. SNP reduced autophagy damage by decreasing the Beclin-1 protein level increased by PbAc. The findings of the present study suggested that SNP attenuates PbAc-induced nephrotoxicity

Beneficial effects of Chrysin on Cadmium-induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways

Cadmium (Cd) is a toxic heavy metal that targets the kidney directly in the body. Chrysin (CHR) is a natural flavonoid with many properties such as antioxidant, anti-inflammatory and anti-apoptotic. The current study discloses new evidence as regards of the curative effects of CHR on Cd-induced nephrotoxicity by regulating oxidative stress, apoptosis, autophagy, and inflammation. Cd was administered orally at a dose of 25 mg/kg body weight alone or in combination with orally administered CHR (25 and 50 mg/kg body weight) for 7 days. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in renal tissue. Renal function tests were also evaluated. Cd caused an increase in serum toxicity markers, lipid peroxidation and a decrease in the activities of antioxidant enzymes. Nrf-2 triggered inflammatory responses by suppressing HO-1 and NQO1 mRNA transcripts and increasing NF-κB, TNF-α, IL-1β and iNOS mRNA transcripts. Cd caused inflammasome by increasing RAGE and NLRP3 mRNA transcripts. In addition, Cd application caused apoptosis by increasing Bax, Apaf-1 and Caspase-3 mRNA transcripts and decreasing Bcl-2 mRNA transcript level. It caused autophagy by increasing the activity of Beclin-1 level. CHR treatment had the opposite effect on all these values and reduced the damage caused by all these signal pathways. Overall, the data of this study indicate that renal damage associated with Cd toxicity could be ameliorated by CHR administration

Sodium Pentaborate Prevents Acetaminophen-Induced Hepatorenal Injury by Suppressing Oxidative Stress, Lipid Peroxidation, Apoptosis, and Inflammatory Cytokines in Rats

Acetaminophen (N-acetyl-p-aminophenol, APAP, or paracetamol) is one of the drugs that may be damaging to the kidneys and liver when used in excess. In this context, it is vital to treat these side effects on the liver and kidneys with various antioxidants. Diseases have been treated using herbal and mineral remedies since ancient times. The mineral boron, found in rocks and water, is a crucial ingredient with multiple positive biological effects. The primary objective of this research is to determine whether or not boron has a protective effect against the toxicity generated by APAP in rats. Male Sprague-Dawley rats were pretreated orally with boron-source sodium pentaborate (B50 and B100 mg/kg) for 6 days by gastric gavage in order to counteract the toxicity caused by a single dose of APAP (1g/kg). APAP increased lipid peroxidation as well as serum BUN, creatinine concentrations, and serum activities of AST, ALP, and ALT by consuming GSH in liver and kidney tissues. In addition, the activity of antioxidative enzymes, including SOD, CAT, and GPx, was diminished. Inflammatory indicators such as TNF-α, IL-1β, and IL-33 were elevated in conjunction with APAP toxicity. In kidney and liver tissues, APAP dramatically increased the activity of caspase-3 and triggered apoptosis. Sodium pentaborate therapy on a short-term basis reduced biochemical levels despite these effects of APAP

Effects of chrysin in cadmium-induced testicular toxicity in the rat; role of multi-pathway regulation

Cadmium (Cd) is a strong toxic agent and causes serious damage to testicular tissues. Chrysin (CHR) is a natural flavonoid with many effective properties, especially antioxidant, anti-inflammatory and anti-apoptotic properties. The current study describes new evidence for the ameliorative effects of CHR on oxidative stress, apoptosis, autophagy and inflammation pathways in Cd-induced testicular tissue toxicity. Methods: Thirty-five male Wistar rats were divided into five groups, control, Cd, CHR, Cd + CHR25, and Cd + CHR50. Cd was administered alone at a dose of 25 mg/kg body weight or in combination with CHR 25 mg/kg and CHR 50 mg/kg for 7 days. Cd and CHR were administered orally. Biochemical, molecular, and histological methods were used to investigate inflammation, apoptosis, autophagy, and oxidant pathways in testicular tissue. Results: Cd increased lipid peroxidation, JAK-2/STAT-3 levels, inflammation-related NF-κB, TNF-α, IL-1β, IL-6, COX-2, and iNOS levels, AKT-2, FOXO1, Bax, Apaf-1 and Caspase-3 levels, autophagic Beclin-1, LC3A and LC3B. The Cd also caused a decrease in the activities of antioxidant enzymes and GSH levels, antiapoptotic Bcl-2 levels. CHR, on the other hand, had the opposite effect of all these Cd-induced changes. Conclusions: Overall, the data of this study indicate that testicular damage associated with Cd toxicity could be ameliorated by CHR administration

Neuroprotective effects of 18 beta-glycyrrhetinic acid against bisphenol A-induced neurotoxicity in rats: involvement of neuronal apoptosis, endoplasmic reticulum stress and JAK1/STAT1 signaling pathway

The exposure to bisphenol A (BPA) is inevitable owing to its common use in the production of polycarbonate plastics. Studies to reduce side effects are gaining importance since BPA causes severe toxicities in important tissues such as testes, lungs, brain, liver and kidney. The current study was planned to study ameliorative effect of 18 beta-glycyrrhetinic acid (18 beta-GA) on BPA induced neurotoxicity. Fourty Wistar albino rats were divided into five equal groups as follows: I-Control group, II-18 beta-GA group (100 mg/kg), III- BPA group (250 mg/kg), IV-250 mg/kg BPA +50 mg/kg 18 beta-GA group, V-250 mg/kg BPA +100 mg/kg 18 beta-GA group. BPA intoxication was associated with increased MDA level while reduced GSH concentration, activities of glutathione peroxidase, superoxide dismutase, and catalase. BPA supplementation caused apoptosis in the brain by up-regulating caspase-3 and Bax levels and down-regulating Bcl-2. BPA also caused endoplasmic reticulum (ER) stress by increasing mRNA transcript levels of PERK, IRE1, ATF-6 and GRP78. Additionally, it was observed that BPA administration activated JAK1/STAT1 signaling pathway and levels of TNF-alpha, NF-kappa B, p38 MAPK and INK in the brain. However, co-treatment with 18 beta-GA at a dose of 50 and 100 mg/kg considerably ameliorated oxidative stress, inflammation, apoptosis, ER stress and JAK1/STAT1 signaling pathway in brain tissue. Overall, the data of this study indicate that brain damage associated with BPA toxicity could be ameliorated by 18 beta-GA administration