Ratlara Malathion ve rutin uygulamaları sonrası akciğer dokularında metalloproteinaz düzeyleri ile oksidatif stres ve apoptoz belirteçlerinin değerlendirilmesi

Malathion (MLT) is an important environmental pollutant in the organophosphate class. Rutin (RUT), on the other hand, is one of the flavonoid family members whose effectiveness against various toxic agents has been extensively studied. In the present study, the effects of MLT and RUT treatments on oxidative stress, apoptosis and metalloproteinases in lung tissues of rats were investigated. In the study, MDA, GSH, Nrf2, HO-1, MMP2, MMP9 and caspase-3 levels in lung tissues were analyzed by biochemical or RT-PCR method after rats received MLT and/or RUT treatment for 28 days. The data showed that MLT-induced MDA levels decreased after RUT treatment. In addition, it was determined that Nrf2 and HO-1 mRNA transcript levels and GSH levels suppressed by MLT approached the control group levels after RUT treatment. MLT up-regulated the expression of metalloproteinases (MMP2 and MMP9) in lung tissues, while RUT down-regulated the expression of these genes. In addition, it was observed that MLT triggered caspase-3 expression, while RUT exerted an anti-apoptotic effect by suppressing caspase-3. As a result, it was determined that while MLT showed toxic effects in the lung tissues of rats through oxidative stress, apoptosis and metalloproteinases, RUT could alleviate these toxic effects.Malathion (MLT), organofosfat sınıfında önemli bir çevresel kirleticidir. Rutin (RUT) ise çeşitli toksik ajanlara karşı etkinliği yoğun olarak araştırılan flavonoid aile üyelerinden biridir. Bu çalışmada, MLT ve RUT tedavilerinin sıçanların akciğer dokularında oksidatif stres, apoptoz ve metalloproteinazlar üzerine etkileri araştırıldı. Çalışmada, sıçanlara 28 gün MLT ve/veya RUT tedavisi verildikten sonra akciğer dokularındaki MDA, GSH, Nrf2, HO-1, MMP2, MMP9 ve kaspaz-3 seviyeleri biyokimyasal veya RT-PCR yöntemi ile analiz edildi. Veriler, MLT ile indüklenen MDA seviyelerinin RUT tedavisinden sonra düştüğünü gösterdi. Ayrıca Nrf2 ve HO-1 mRNA transkript düzeyleri ile MLT tarafından baskılanan GSH düzeylerinin RUT tedavisi sonrası kontrol grubu düzeylerine yaklaştığı belirlendi. MLT, akciğer dokularında metalloproteinazların (MMP2 ve MMP9) ekspresyonunu yukarı doğru düzenlerken, RUT bu genlerin ekspresyonunu aşağı regüle etti. Ayrıca MLT'nin kaspaz-3 ekspresyonunu tetiklediği, RUT'nin ise kaspaz-3'ü baskılayarak anti-apoptotik etki gösterdiği gözlendi. Sonuç olarak, MLT'nin oksidatif stres, apoptoz ve metalloproteinazlar yoluyla sıçanların akciğer dokularında toksik etkiler gösterirken, RUT'nin bu toksik etkileri azaltabileceği belirlendi

Evaluation of the effects of chrysin on diclofenac-Induced cardiotoxicity in rats by the markers of oxidative stress, endoplasmic reticulum stress and apoptosis

Diklofenak (DF), steroid olmayan anti-inflamatuar ilaçlar arasındadır ve yüksek dozlarda kalp dahil çeşitli dokularda toksik etkiler göstermektedir. Krisin (KRS) antioksidan ve anti-apoptotik gibi birçok yararlı etkiye sahiptir. Sunulan çalışmada DF ile indüklenen kardiyotoksisite üzerine KRS’nin etkileri araştırılmıştır. Bu amaçla Sprague Dawley ratlara DF ve/veya KRS uygulamaları yapıldıktan sonra kalp dokularında oksidatif stres, endoplazmik retikulum stresi ve apoptoz belirteçleri ve serum CK-MB seviyeleri analiz edildi. Elde edilen veriler DF ile indüklenen oksidatif stresin KRS uygulamasından sonra SOD, CAT ve GPx enzimlerinin ekspresyonlarının tetiklenmesi ve GSH seviyelerinin artması ile hafiflediğini ve MDA seviyelerinde azalma meydana geldiğini göstermektedir. Ayrıca ER stres belirteçleri olan ve DF’nin indüklediği ATF-6, PERK, IRE1 ve GRP78 ekspresyonlarının KRS tedavisinden sonra aşağı yönlü düzenlendiği belirlendi. ER stresi ile bağlantılı olarak KRS’nin Bax ve Kaspaz-3 ekspresyonlarını baskıladığı ve Bcl-2 ekspresyonunu arttırdığı da elde edilen veriler arasındadır. Ayrıca kalp hasarının önemli bir göstergesi olan CK-MB seviyelerinin KRS uygulamasından sonra azaldığı görüldü. Sonuç olarak DF’nin neden olduğu kardiyotoksisiteye karşı KRS’nin önemli bir koruma sağladığı tespit edildi.Diclofenac (DF) is among non-steroidal anti-inflammatory drugs and in high doses it has toxic effects on various tissues, including the heart. Chrysin (CRS) has many beneficial effects such as antioxidant and anti-apoptotic. In the present study, the effects of CRS on DF-induced cardiotoxicity were investigated. For this purpose, after DF and/or CRS treatments were applied to Sprague Dawley rats, the markers of oxidative stress, endoplasmic reticulum stress and apoptosis in heart tissues and serum CK-MB levels were analyzed. The data obtained displayed that oxidative stress induced by DF was alleviated by triggering the expression of SOD, CAT and GPx enzymes and increasing GSH levels after CRS administration, and a decrease in MDA levels occurred. It was also determined that the expressions of ATF-6, PERK, IRE1 and GRP78, which are ER stress markers and induced by DF, were downregulated after CRS treatment. Additionally, CRS suppressed Bax and Caspase-3 expressions and increased Bcl-2 expression in connection with ER stress. Another finding of this study demonstrated that CK-MB levels, which are an important indicator of heart damage, decreased after CRS administration. As a result, CRS provided a significant protection against cardiotoxicity caused by DF

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

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

Molecular and biochemical investigation of the protective effects of rutin against liver and kidney toxicity caused by malathion administration in a rat model

Widely used malathion (MLT) causes environmental pollution, leading to toxicity in many living things, including humans. Rutin (RUT) is a flavonoid with various biological properties. In the present study, the protective effects of rutin against liver and kidney toxicity caused by malathion were investigated. In the study, MLT (100 mg/kg) and RUT (50 or 100 mg/kg) were administered to rats alone or in combination for 28 days. Then, oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy markers in liver and kidney tissues were analyzed by biochemical and molecular methods. The results showed that MLT caused oxidative stress in both tissues, while RUT showed antioxidant properties and protected these tissues from oxidative damage. Moreover, MLT upregulated the expressions of ATF-6, PERK, IRE1, GRP78, and CHOP, leading to ERS. However, RUT alleviated ER stress and suppressed these markers. The study also found that MLT increased inflammatory, apoptotic, and autophagic markers. All these factors affected liver and kidney functions and caused an increase in plasma ALT, AST, urea, and creatinine levels. On the other hand, it has been observed that RUT may protect liver and kidney tissues from the destructive effect of MLT by showing anti-inflammatory, anti-apoptotic, and anti-autophagic properties. Thus, it was determined that ALT, AST, urea, and creatinine levels decreased after RUT treatment. As a result, it was observed that MLT had a toxic effect on the liver and kidney tissues of rats, and it was determined that this toxicity could be alleviated by RUT treatment

Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways

Paclitaxel (PTX) is a widely used chemotherapeutic drug particularly effective against lung, breast, and ovarian cancer, though its usefulness is limited due to its multi-organ toxicity. The mechanisms underlying PTX toxicity are currently not yet known and there are no approved treatments for its control or prevention. This study aimed to investigate whether hesperidin (HSP) had a protective effect on paclitaxel-induced hepatotoxicity and nephrotoxicity from biochemical, and molecular perspectives. The rats were administered PTX 2 mg/kg, b.w. intraperitoneally for the first 5 consecutive days, then 100 or 200 mg/kg b.w. HSP orally for 10 consecutive days. Our results demonstrated that HSP decreased the PTX induced lipid peroxidation, improved the serum hepatic and renal functions (by decreasing the levels of AST, ALT, ALP, urea, and creatinine), and restored the liver and kidney antioxidant armory (SOD, CAT, GPx, and GSH). HSP also significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-1β, IL-6, MAPK 14, Caspase-3, Bax, LC3A, LC3B, MMP2, and MMP9 whereas caused an increase in levels of Nrf2, HO-1, and Bcl-2 in the kidney and liver of PTX-induced rats. In addition, caspase-3, Bax, and Bcl-2 protein levels were examined by Western blot analysis, and it was determined that HSP decreased caspase-3 and Bax protein levels, but increased Bcl-2 protein levels. The findings of the study suggest that HSP has chemopreventive potential against PTX-induced hepatorenal toxicity plausibly through the attenuation of oxidative stress, inflammation, apoptosis, and autophagy

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

Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite-induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats

Arsenic (As) is a highly toxic metalloid. Carvacrol (CAR) is the active ingredient of Lamiaceae plants and has various biological and pharmacological properties. The present study investigated the protective effects of carvacrol (CAR) against testicular toxicity induced by sodium arsenite (SA). Rats were given SA (10 mg/kg) and/or CAR (25 or 50 mg/kg) for 14 days. Semen analyzes showed that CAR increased sperm motility and decreased the percentage of abnormal and dead sperm. It was determined that the oxidative stress induced by SA decreased with the increase of Nrf-2 and HO-1 expressions, SOD, CAT, GPx, and GSH levels, and MDA levels decreased after CAR treatment. It was observed that autophagy and inflammation triggered by SA in testicular tissue were alleviated by suppressing the expressions of LC3A, LC3B, MAPK-14, NF-κB, TNF-α, IL-1β, iNOS, and COX-2 biomarkers in rats given CAR. Also, CAR treatment suppressed SA-induced apoptosis by inhibiting Bax and Caspase-3 expressions in testicles and up-regulating Bcl-2 expression. Histopathological analyzes showed that rats given SA had deterioration in tubule structure and spermatogenesis cell line, especially a serious loss of spermatogonia cells, atrophy of seminiferous tubules, and deterioration of germinal epithelium. In the group given CAR, the germinal epithelium and connective tissue were in normal morphological structure and an increase in seminiferous tubule diameters was observed. As a result, it was determined that oxidative stress, inflammation, autophagy, and apoptosis induced by SA were suppressed by CAR, thus protecting the testicular tissue from damage and increasing semen quality

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