Naringin protects against paclitaxel-induced toxicity in rat testicular tissues by regulating genes in pro-inflammatory cytokines, oxidative stress, apoptosis, and JNK/MAPK signaling pathways.

Paclitaxel (PTX), which is actively used in the treatment of many types of cancer, has a toxic effect by causing increased oxidative stress in testicular tissues. Naringin (NRG) is a natural flavonoid found in plants, and its antioxidant properties are at the forefront. This study aims to investigate the protective feature of NRG in PTX-induced testicular toxicity. Thirty-five male Sprague rats were divided into five groups: control, NRG, PTX, PTX + NRG50, and PTX + NRG100. Rats were administered PTX (2 mg/kg, BW) intraperitoneally once daily for the first 5 days. Then, between the 6th and 14th days, NRG (50 and 100 mg/kg) was administered orally once a day. NRG reduced PTX-induced lipid peroxidation and increased testicular tissue antioxidant capacity (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). While NRG reduces the mRNA expression levels of nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1 beta, cyclooxygenase-2, interleukin-6, inducible-nitric oxide synthase, mitogen-activated protein kinase 14 (MAPK)14, MAPK15, c-Jun N-terminal kinase, P53, Apaf1, Caspase3, Caspase6, Caspase9, and Bax in testicular tissues; it caused an increase in Nrf2, HO-1, NQO1 and Bcl-2 levels. NRG also improved the structural and functional integrity of testicular tissue disrupted by PTX. PTX-induced sperm damage was alleviated by NRG. NRG showed a protective effect by alleviating the PTX-induced testicular toxicity by increasing oxidative stress, inflammation, apoptosis, and autophagy.

The ameliorative effects of chrysin on bortezomib-induced nephrotoxicity in rats: Reduces oxidative stress, endoplasmic reticulum stress, inflammation damage, apoptotic and autophagic death.

AIM: Bortezomib is a proteasome inhibitor antineoplastic agent that was the first to be approved for cancer treatment. One of bortezomib's most prominent dose-limiting effects is nephrotoxicity; the underlying mechanism is believed to be oxidative stress. Chrysin is a compound found actively in honey and many plant species and stands out with its antioxidant properties. The present study aimed to determine the ameliorative effects of chrysin in bortezomib-induced nephrotoxicity. MATERIAL-METHOD: Thirty-five male Wistar rats were divided into control, BTZ, CHR, BTZ + CHR25, and BTZ + CHR50. Biochemical, molecular, Western blot, and histological methods analyzed renal function indicators, oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and damage pathways. RESULTS: Chrysin decreased oxidative stress by reducing oxidants (MDA) and increasing antioxidants (SOD, CAT, Gpx, GSH, Nrf-2, HO-1, NQO1). Chrysin reduced endoplasmic reticulum stress by decreasing ATF-6, PERK, IRE1, and GRP-78 levels. Chrysin reduced inflammation damage by inhibiting the NF-κB pathway. Chrysin exhibited protective properties against apoptotic damage by decreasing Bax and Caspase-3 levels and increasing Bcl-2 levels. In addition, chrysin improved renal function and structural integrity and exhibited healing properties against toxic damage in tissue structure. CONCLUSION: Overall, chrysin exhibited an ameliorative effect against bortezomib-induced nephrotoxicity.

Therapeutic Potential of Silymarin in Mitigating Paclitaxel-Induced Hepatotoxicity and Nephrotoxicity: Insights into Oxidative Stress, Inflammation, and Apoptosis in Rats.

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits. Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways. Study Design: Experimental animal model. Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models. Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups (p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX (p < 0.05). Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes.

Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways.

Objectives: This study aimed to investigate the effects of zingerone (ZNG) treatment on testicular toxicity in rats induced by sodium arsenite (SA). Materials and Methods: In the study, five groups were formed (n=7) and the experimental groups were designated as follows; Vehicle group, ZNG group, SA group, SA+ZNG 25 group, and SA+ZNG 50 group. While SA was administered orally to rats at 10 mg/kg/bw, ZNG was given to rats orally at 25 and 50 mg/kg/bw doses for 14 days. Results: As a result of the presented study, an increase was observed in the MDA contents of the testicular tissue of the rats administered SA, while significant decreases were observed in GSH levels, SOD, CAT, and GPx activities. The mRNA transcript levels of the pro-inflammatory genes NF-κB, TNF-α, IL-1ß, and IL-6 were triggered after SA administration. Additionally, SA administration caused inflammation by increasing RAGE, NLRP3, and JAK-2/STAT3 gene expression. Moreover, endoplasmic reticulum (ER) stress occurred in the testicular tissues of SA-treated rats and thus ATF-6, PERK, IRE1, and GRP78 genes were up-regulated. SA caused apoptosis by up-regulating Bax and Caspase-3 expressions and inhibiting Bcl-2 expression in testicles. SA caused histological irregularities in the testicles, resulting in decreased sperm quality. Conclusion: ZNG treatment reduced SA-induced oxidative stress, ER stress, inflammation, apoptosis, and histological irregularities in the testicles while increasing sperm quality. As a result, it was observed that ZNG could alleviate the toxicity caused by SA in the testicles.

Sinapic acid protects against lead acetate-induced lung toxicity by reducing oxidative stress, apoptosis, inflammation, and endoplasmic reticulum stress damage.

Lead acetate (PbAc) is a compound that produces toxicity in many tissues after exposure. Sinapic acid (SNP) possesses many biological and pharmacological properties. This study aimed to investigate the efficacy of SNP on the toxicity of PbAc in lung tissue. PbAc was administered orally at 30 mg/kg and SNP at 5 or 10 mg/kg for 7 days. Biochemical, genetic, and histological methods were used to investigate inflammatory, apoptotic, endoplasmic reticulum stress, and oxidative stress damage levels in lung tissue. SNP administration induced PbAc-reduced antioxidant (GSH, SOD, CAT, and GPx) and expression of HO-1 in lung tissue. It also reduced MDA, induced by PbAc, and thus alleviated oxidative stress. SNP decreased the inflammatory markers NF-κB, TNF-α and IL-1ß levels induced by PbAc in lung tissue and exhibited anti-inflammatory effect. PbAc increased apoptotic Bax, Apaf-1, and Caspase-3 mRNA transcription levels and decreased anti-apoptotic Bcl-2 in lung tissues. SNP decreased apoptotic damage by reversing this situation. On the other hand, SNP regulated these markers and brought them closer to the levels of the control group. PbAc caused prolonged ER stress by increasing the levels of ATF6, PERK, IRE1α, GRP78 and this activity was stopped and tended to retreat with SNP. After evaluating all the data, While PbAc caused toxic damage in lung tissue, SNP showed a protective effect by reducing this damage.

Protective effects of naringin against oxaliplatin-induced testicular damage in rats: Involvement of oxidative stress, inflammation, endoplasmic reticulum stress, apoptosis, and histopathology.

Objectives: Oxaliplatin (OXL) is a platinum-based chemotherapeutic agent widely used in the treatment of colorectal cancer. Unfortunately, this important drug also causes unwanted side effects such as neuropathy, ototoxicity, and testicular toxicity. This study aimed to investigate the possible protective effects of naringin (NRG) against OXL-induced testicular toxicity in rats. Materials and Methods: In the present study, rats were injected with OXL (4 mg/kg, b.w./day, IP) in 5% dextrose solution 30 min after oral administration of NRG (50 and 100 mg/kg, b.w./day) on the 1st, 2nd, 5th, and 6th days. Then, the rats were sacrificed on the 7th day and the testicular tissues were removed. Results: The results showed that NRG decreased (P<0.001) lipid peroxidation, increased (P<0.001) the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the levels of glutathione (GSH), and also maintained the testis histological architecture and integrity. NRG decreased the levels of apoptosis-related markers such as caspase-3, Bax, and Apaf-1 and increased Bcl2 in the OXL-induced testicular toxicity (P<0.001). In addition, NRG reversed the changes in mRNA transcript levels of oxidative stress, inflammation, and endoplasmic reticulum stress parameters such as Nrf2, HO-1, NQO1, RAGE, NLRP3, MAPK-14, STAT3, NF-κB, IL-1ß, TNF-α, PERK, IRE1, ATF6, and GRP78 in OXL-induced testicular toxicity (P<0.001). Conclusion: Our results demonstrated that NRG can protect against OXL-induced testicular toxicity by enhancing the anti-oxidant defense system and suppressing apoptosis, inflammation, and endoplasmic reticulum stress.

Zingerone attenuates sciatic nerve damage caused by sodium arsenite by inhibiting NF-κB, caspase-3, and ATF-6/CHOP pathways and activating the Akt2/FOXO1 pathway.

Objectives: In the present study, the potential protective effects of zingerone (ZNG) against sciatic nerve damage caused by sodium arsenite (SA), a common environmental pollutant, were evaluated by various biochemical, molecular, and histological methods. Materials and Methods: In the study, SA and ZNG were given to 35 male Sprague Dawley rats for 14 days. At the end of the period, the sciatic nerve tissues were taken and the markers involved in oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis were analyzed. Results: The data obtained showed that SA decreased glutathione (GSH) levels and increased malondialdehyde (MDA) levels in the sciatic nerve tissue. However, it was determined that these markers approached the control group levels due to the anti-oxidant properties of ZNG. While SA triggered endoplasmic reticulum stress and apoptosis pathways, ZNG suppressed them. Moreover, SA up-regulated inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1ß), and neuronal nitric oxide synthases (nNOS) in the sciatic nerves and caused neuro-inflammation and inhibited cell survival by suppressing serine/threonine-protein kinase 2 (Akt2) and forkhead box protein O1 (FOXO1) genes. It has also been shown histopathologically that SA causes degeneration in the sciatic nerves. In contrast, ZNG suppressed neuro-inflammation, activated Akt2/FOXO1 signaling, and repaired histological irregularities. Conclusion: In general, SA caused oxidative stress, inflammation, ER stress, and apoptosis in the sciatic nerves of rats, causing damage to the tissues, however, ZNG suppressed these pathways and protected the sciatic nerves from the destructive effect of SA.

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-1ß, 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. This study showed that boron protects rats from the harmful effects of APAP by acting as an anti-inflammatory, antioxidant, and anti-apoptotic agent.

Hesperidin counteracts chlorpyrifos-induced neurotoxicity by regulating oxidative stress, inflammation, and apoptosis in rats.

Chlorpyrifos (CPF), considered one of the most potent organophosphates, causes a variety of human disorders including neurotoxicity. The current study was designed to evaluate the efficacy of hesperidin (HSP) in ameliorating CPF-induced neurotoxicity in rats. In the study, rats were treated with HSP (orally, 50 and 100 mg/kg) 30 min after giving CPF (orally, 6.75 mg/kg) for 28 consecutive days. Molecular, biochemical, and histological methods were used to investigate cholinergic enzymes, oxidative stress, inflammation, and apoptosis in the brain tissue. CPF intoxication resulted in inhibition of acetylcholinesterase (AChE) and butrylcholinesterase (BChE) enzymes, reduced antioxidant status [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione (GSH)], and elevation of malondialdehyde (MDA) levels and carbonic anhydrase (CA) activities. CPF increased histopathological changes and immunohistochemical expressions of 8-OHdG in brain tissue. CPF also increased levels of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-κB) while decreased levels of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α). Furthermore, CPF increased mRNA transcript levels of caspase-3, Bax, PARP-1, and VEGF, which are associated with apoptosis and endothelial damage in rat brain tissues. HSP treatment was found to protect brain tissue by reducing CPF-induced neurotoxicity. Overall, this study supports that HSP can be used to reduce CPF-induced neurotoxicity.

Carvacrol Reduces Mercuric Chloride-Induced Testicular Toxicity by Regulating Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Histopathological Changes.

Mercuric chloride (HgCl2) is a heavy metal that is toxic to the human body. Carvacrol (CAR) is a flavonoid found naturally in plants and has many biological and pharmacological activities including anti-inflammatory, antioxidant, and anticancer activities. This study aimed to investigate the efficacy of CAR in HgCl2-induced testicular tissue damage. HgCl2 was administered intraperitoneally at a dose of 1.23 mg/kg body weight alone or in combination with orally administered CAR (25 mg/kg and 50 mg/kg body weight) for 7 days. Biochemical and histological methods were used to investigate oxidative stress, inflammation, apoptosis, and autophagy pathways in testicular tissue. CAR treatment increased HgCl2-induced decreased antioxidant enzyme (SOD, CAT, and GPx) activities and GSH levels. In addition, CAR reduced MDA levels, a marker of lipid peroxidation. CAR decreased the levels of inflammatory mediators NF-κB, TNF-α, IL-1ß, COX-2, iNOS, MAPK14, MAPK15, and JNK. The increases in apoptotic Bax and Caspase-3 with HgCl2 exposure decreased with CAR, while the decreased antiapoptotic Bcl-2 level increased. CAR reduced HgCl2-induced autophagy damage by increasing Beclin-1, LC3A, and LC3B levels. Overall, the data from this study suggested that testicular tissue damage associated with HgCl2 toxicity can be mitigated by CAR administration.

Effect of syringic acid on oxidative stress, autophagy, apoptosis, inflammation pathways against testicular damage induced by lead acetate.

BACKGROUND: Heavy metals are one of the environmental pollutants. Lead (Pb) is one of the most common of these heavy metals. In this study, it was aimed at investigating the effects of syringic acid (SA) against testicular toxicity in rats administered lead acetate (PbAc). METHODS: In the present study, a total of 35 Sprague-Dawley rats, 7 in each group, were used. The rats were divided into 5 groups, with 7 male rats in each group. Rats were given PbAc and SA orally for 7 days. The effects of PbAc and SA on epididymal sperm quality and apoptosis, inflammation, oxidative stress and histopathological changes in testicular tissue were determined. RESULTS: While PbAc disrupted the seminiferous tubules and produced atrophic images, SA corrected these histological abnormalities. PbAc adminisration significantly reduced the levels of SOD, GSH, GPx, CAT, NRF-2 and NQO1 and significantly increased the levels of MDA and 8-OHdG in the testicular tissue of rats, while SA improved this situation. NF-κB, TNF-α, IL-1ß, NLRP3, RAGE, ATF6, PERK, IRE1, CHOP, and GRP78 genes expression levels increased with PbAc administration, however these levels decreased with SA administration. In addition, PbAc increased the levels of apoptotic markers Bax, Caspase-3 and APAF-1 and decreased the level of Bcl-2, while SA improved this situation. It was observed that PbAc significantly reduced sperm quality in rats, while SA positively affected sperm quality. CONCLUSION: As a result, SA administered against PbAc-induced testicular dysfunction in rats can provide effective protection at doses of 25 mg/kg/bw and 50 mg/kg/bw.

Morin provides therapeutic effect by attenuating oxidative stress, inflammation, endoplasmic reticulum stress, autophagy, apoptosis, and oxidative DNA damage in testicular toxicity caused by ifosfamide in rats.

Objectives: In the present study, it was evaluated whether morin has a protective effect on testicular toxicity caused by ifosfamide (IFOS), which is used in the treatment of various malignancies. Materials and Methods: For this purpose, 100 or 200 mg/kg morin was given to Sprague Dawley rats for 2 days, and a single dose (500 mg/kg) IFOS was administered on the 2nd day. At the 24th hr of IFOS administration, animals were decapitated and testicular tissues were taken and the status of oxidative stress, inflammation, endoplasmic reticulum stress (ERS), autophagy, and apoptosis markers were analyzed by biochemical, molecular, and histopathological methods. Results: According to the data obtained, it was determined that IFOS caused oxidative stress in testicular tissues. It was observed that inflammation, ERS, autophagy, apoptosis, and oxidative DNA damage occurred with oxidative stress. Morin treatment suppressed oxidative stress. Morin showed anti-inflammatory effects by reducing TNF-α and IL-1ß protein levels. It also increased the mRNA transcript levels of the ERS marker ATF-6, PERK, IRE1, GRP-78, and CHOP genes, and the apoptosis marker genes Bax, Casp-3, and apaf-1. It up-regulated the anti-apoptotic protein Bcl-2 gene and the cell survival signal AKT-2 gene. Morin caused a decrease in beclin-1 protein levels and showed an anti-autophagic effect. In addition, morin attenuated oxidative DNA damage and decreased 8-OHdG immune-positive cell numbers. Conclusion: As a result, it was observed that IFOS caused cellular damage by activating various signaling pathways in testicular tissue, while morin exhibited protective properties against this damage.

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-1ß, 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.

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

Objectives: 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.

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

BACKGROUND: 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-1ß, 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.

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-1ß, 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.

The protective effects of chrysin on cadmium-induced pulmonary toxicity; a multi-biomarker approach.

This study aimed to determine the potential protective effects of chrysin (CHR) on experimental cadmium (Cd)-induced lung toxicity in rats. To this end, rats were divided into five groups; Control, CHR, Cd, Cd + CHR25, Cd + CHR50. In the study, rats were treated with CHR (oral gavage, 25 mg/kg and 50 mg/kg) 30 min after giving Cd (oral gavage, 25 mg/kg) for 7 consecutive days. The effects of Cd and CHR treatments on oxidative stress, inflammatory response, ER stress, apoptosis and tissue damage in rat lung tissues were determined by biochemical and histological methods. Our results revealed that CHR therapy for Cd-administered rats could significantly reduce MDA levels in lung tissue while significantly increasing the activity of antioxidant enzymes (SOD, CAT, GPx) and GSH levels. CHR agent exerted antiinflammatory effect by lowering elevated levels of NF-κB, IL-1ß IL-6, TNF-α, RAGE and NRLP3 in Cd-induced lung tissue. Moreover CHR down-regulated Cd-induced ER stress markers (PERK, IRE1, ATF6, CHOP, and GRP78) and apoptosis markers (Caspase-3, Bax) lung tissue. CHR up-regulated the Bcl-2 gene, an anti-apoptotic marker. Besides, CHR attenuated the side effects caused by Cd by modulating histopathological changes such as hemorrhage, inflammatory cell infiltration, thickening of the alveolar wall and collagen increase. Immunohistochemically, NF-κB and Caspase-3 expressions were intense in the Cd group, while these expressions were decreased in the Cd + CHR groups. These results suggest that CHR exhibits protective effects against Cd-induced lung toxicity in rats by ameliorating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress and histological changes.

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-1ß 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.

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-1ß, 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.

Carvacrol protects against λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity by modulating oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy.

λ-Cyhalothrin, a type II synthetic pyrethroid, has been widely used in households, agriculture, public health, and gardening to control insect pests. Despite its widespread usage, it is known to induce a variety of adverse effects, including hepatotoxicity and nephrotoxicity. The goal of this study was to investigate the protective effect of carvacrol, which has antioxidant, anti-inflammatory, anti-apoptotic, and some other properties, on λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity 35 male Sprague-Dawley rats were randomly divided into five groups for this purpose: I-Control group: II-CRV group (50 mg/kg carvacrol), III-LCT group (6.23 mg/kg LCT), IV-LCT + CRV 25 group (6.23 mg/kg LCT + 25 mg/kg carvacrol), and V-LCT + CRV 50 group (6.23 mg/kg LCT + 50 mg/kg carvacrol). Using biochemical, real-time PCR, and western blotting methods, the collected tissues were analyzed. While λ-Cyhalothrin treatment increased MDA levels, which are indicated of lipid peroxidation, but reduced SOD, CAT, GPx activities, and GSH levels. After receiving carvacrol therapy, the degree of oxidative stress reduced as the values of these parameters approached those of the control group. Increased inflammation, apoptosis, endoplasmic reticulum stress, and autophagy with λ-Cyhalothrin administration reduced with carvacrol co-administration, and liver and kidney tissues were protected from damage, depending on the degree of oxidative stress. After considering all of these data, it was discovered that λ-Cyhalothrin-induced oxidative stress, inflammation, apoptosis, endoplasmic reticulum stress, and autophagy in the liver and kidneys; however, carvacrol protected the tissues from damage. Our findings indicate that carvacrol may be a promising protective agent in λ-Cyhalothrin-induced hepatotoxicity and nephrotoxicity.