Okadaic acid enhances NfKB, TLR-4, caspase 3, ERK ½, c-FOS, and 8-OHdG signaling pathways activation in brain tissues of zebrafish larvae.

This study was designed to investigate the potential neuronal damage mechanism of the okadaic acid (OA) in the brain tissues of zebrafish embryos by evaluating in terms of immunofluorescence of Nf KB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG signaling pathways. We also evaluated body malformations. For this purpose, zebrafish embryos were exposed to 0.5 µg/ml, 1 µg/ml and 2.5 µg/ml of OA for 5 days. After application, FITC/GFP labeled protein-specific antibodies were used in immunofluorescence assay for NfKB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG respectively. The results indicated that OA caused immunofluorescence positivity of NfKB, TLR-4, caspase 3, ERK ½, c-FOS and 8-OHdG in a dose-dependent manner in the brain tissues of zebrafish embryos. Pericardial edema (PE), nutrient sac edema (YSE) and body malformations, tail malformation, short tail and head malformation (BM) were detected in zebrafish embryos. These results suggest that OA induces neuronal damage by affecting the modulation of DNA damage, apoptotic, and inflammatory activities in the brain tissues of zebrafish embryos. The increase in signaling pathways shows that OA can cause damage in the structure and function of brain nerve cells. Our results provide a new basis for the comprehensive assessment of the neural damage of OA and will offer enable us to better understand molecular the mechanisms underlying the pathophysiology of OA toxicity.

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.

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.

The effects of low-level laser therapy on polycystic ovarian syndrome in rats: three different dosages.

The main objective of this in vivo study was to investigate the effect of different low-level laser therapy (LLLT) doses on polycystic ovary syndrome (PCOS). In the present experimental study, a single dosage of estradiol valerate (EV) was administered to induce PCOS in female rats. After administration of the EV for induction of PCOS, rats were divided into 5 groups (n = 8/group): C group (animals that were not exposed to any form of procedure), PC group (no treatment following EV induction), L1 group (1 J/cm2 LLLT treatment following EV induction), L2 group (2 J/cm2 LLLT treatment following EV induction), L3 group (6 J/cm2 LLLT treatment following EV induction). The results indicated that no significant difference was found in the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P4) between the C and L2 groups (p < 0.05). Although the serum levels of testosterone (T) were significantly higher in the C group compared with other groups (p < 0.05), the L2 group was determined to be the closest to the C group. Additionally, the LH, FSH, and T receptor level of the L2 group was closest to the C group. In conclusion, a 2 J/cm2 dosage of LLLT (L2 group) can be considered the most potentially effective treatment of PCOS in the rat. However, more studies are needed to determine the optimal dose of LLLT for the treatment of PCOS.

The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis.

Morin is a flavonoid and broadly found in white berry and cranberry branch. Ifosfamide (IFOS) is known as an anticancer and cytotoxic drug especially on the liver. This study aimed to explore the potential protective effects of Morin against IFOS-induced liver toxicity in rats. The model group of rats received a single injection of IFOS (500 mg/kg; i.p.) at day 2, whereas the protective groups of rats were given two different doses of Morin (100 and 200 mg/kg; given by gavage) at days 1 and 2. All animals were then culled 24 h post-IFOS injection. We observed that IFOS caused liver injury, oxidative stress, inflammation, DNA damage, and apoptosis. However, Morin decreased the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) (p < 0.05). While Morin contributed to the recovery of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) levels, Morin decreased the levels of malondialdehyde (MDA) induced by IFOS in the liver (p < 0.05). Besides, the levels of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and P53 measured by ELISA test were reduced via Morin administration (p < 0.05). Lastly, the mRNA transcript levels of Bax, Apaf-1, Bcl-2, Bcl-xL, and inducible nitric oxide synthase (iNOS) determined by RT-PCR were down-regulated in the Morin groups (p < 0.05). These results indicate that Morin plays a protective role by reducing oxidative stress, inflammation, and apoptosis in the IFOS-induced liver injury in rats.

Roles of apoptosis and autophagy in natural rabies infections.

The aim of this study was to investigate the activity of apoptosis and autophagy in animals (cows, horses, donkeys, dogs and cats) naturally infected with rabies by using immunohistochemistry, immunofluorescence, and qPCR. The mRNA transcript levels of caspase-3, Bax, Bcl2 and LC3B were determined with qPCR. Caspase-3 and AIF immunopositivity were not observed in the immunohistochemical and immunofluorescence staining, whereas LC3B immunopositivity was determined intensively in the infected animals compared to the control groups. LC3B immunopositivity was detected in the cytoplasm of the Purkinje cells in the cerebellum of the cows, horses and donkeys, and also in the cytoplasm of the neurons in the cornu ammonis of the dogs and cats. While the expression levels of caspase-3 and Bax were downregulated, the Bcl2 expression was up-regulated in the infected animals compared to the uninfected animals. In addition, the LC3B levels were found to be significantly higher in the infected animals. To the best of our knowledge, this work represents the first report of neuronal death in the central nervous system by autophagy, rather than by caspase-dependent or AIF-containing caspase-independent apoptosis.

Protective Effects of Curcumin Against Paclitaxel-Induced Spinal Cord and Sciatic Nerve Injuries in Rats.

Paclitaxel (PTX) is an antineoplastic agent commonly used in the treatment of solid tumors and is known to cause dose-limiting peripheral neurotoxicity. This study was performed to evaluate the protective effect of curcumin (CUR) against PTX-induced spinal cord and sciatic nerve injuries in rats. The rats were administered PTX (2 mg/kg, BW) intraperitoneally for the first 5 consecutive days followed by administration of CUR (100 and 200 mg/kg, BW daily in corn oil) orally for 10 days. Our results showed that CUR significantly reduced mRNA expression levels of NF-κB, TNF-α, IL-6, iNOS and GFAP whereas caused an increase in levels of Nrf2, HO-1 and NQO1 in the spinal cord and sciatic nerve of PTX-induced rats. In addition, CUR suppressed the activation of apoptotic and autophagic pathways by increasing Bcl-2 and Bcl-xL, and decreasing p53, caspase-3, Apaf-1, LC3A, LC3B and beclin-1 mRNA expression levels. The results showed that CUR also maintained the spinal cord and sciatic nerve histological architecture and integrity by both LFB staining and H&E staining. Immunohistochemical expressions of 8-OHdG, caspase-3 and LC3B in the PTX-induced spinal cord tissue were decreased after administration of CUR. Taken together, our findings demonstrated that CUR has protective effects on PTX-induced spinal cord and sciatic nerve injuries in rats.

How does elevated water temperature affect fish brain? (A neurophysiological and experimental study: Assessment of brain derived neurotrophic factor, cFOS, apoptotic genes, heat shock genes, ER-stress genes and oxidative stress genes).

Water temperature is one of the most important environmental factors affecting the growth and survival of fish. Increased water temperature became a global problem and it is estimated that there will be an increase in water temperature due to global climate change. The physiological mechanism for the effects of high water temperature on the fish brain is not fully known. In the present study, fish were exposed to different temperatures (10 °C/15 °C/20 °C/25°) and brain tissues were sampled 2 h-4h-6h-8h per hour respectively and then we investigated transcriptional changes of BDNF, cFOS, apoptotic genes (caspase 3, Bax, Bcl2), heat shock genes (Hsp70 and Hsp 90) ER-Stress genes (grp78, atf6, and ire1) and oxidative stress genes (CAT, SOD, and GPx) and also immunoflourescence changes of BDNF and cFOSin rainbow trout brain. The results indicated that high temperature stress lead to physiological changes in the fish brain by causing a decrease in mRNA expression levels of CAT, SOD, GPx and Bcl2 and by causing an increase in mRNA expression of BDNF, cFOS, apoptotic genes (caspase 3, Bax), heat shock genes (Hsp70 and Hsp 90) ER-Stress genes (grp78, atf6, and ire1). This study will provide important information to elucidate the physiological mechanisms related to the effects of high water temperature on the fish brain.

Hesperidin protects against the chlorpyrifos-induced chronic hepato-renal toxicity in rats associated with oxidative stress, inflammation, apoptosis, autophagy, and up-regulation of PARP-1/VEGF.

In this study, we investigated the effects of hesperidin (HSP) on oxidants/antioxidants status, inflammation, apoptotic, and autophagic activity in hepato-renal toxicity induced by chronic chlorpyrifos (CPF) exposure in rats. We used a total of 35 male albino rats in five groups of seven: control, HSP 100, CPF, CPF + HSP50, and CPF + HSP100. After rats were sacrificed, blood, liver, and kidney samples were collected. Serum levels of aspartate aminotransferases (ALT and AST), alkaline phosphatase (ALP), creatinine, and urea were tested. Then, contents of the superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), glutathione peroxidase (GPx), and glutathione (GSH) were measured to detect the level of oxidative stress in rat liver and renal tissues. We measured inflammatory and autophagy markers of chlorpyrifos induced oxidative stress in the liver and kidney tissues including TNF-α, iNOS, IL-1 ß, COX-2, NF-κB, MAPK14, and Beclin-1 using ELISA. Histopathological findings were also examined followed by immunohistochemical determination of 8-OHdG expression. Real-time PCR (RT-PCR) was used to examine Cas-3, Bax, Bcl-2, PARP-1, and VEGF, which are associated with apoptosis, autophagy, DNA, and endothelial damage, respectively. In addition, PARP-1 activity was supported by western blot and immunofluorescence, VEGF activity was supported by western blot methods. Treatment with HSP reduced the effect of CPF on ALT, AST, ALP, and total proteins, and increased its effect on tissue antioxidants. PARP/VEGF, apoptotic, pro-apoptotic, anti-apoptotic, and autophagic gene expressions were regulated, and Caspase-3 and Bax expressions were decreased; Bcl-2 expression increased in both the liver and kidney samples, and positivity of 8-OHdG and PARP-1 were reduced in the CPF plus HSP-treated group. Overall, the study demonstrates that HSP may reduce the effects of hepato-renal toxicity caused by CPF by regulating oxidative stress, inflammation, apoptosis, autophagy, and PARP/VEGF genes at biochemical, cellular, and molecular levels.

Teratogenic and Neurotoxic Effects of n-Butanol on Zebrafish Development.

In recent years, n-butanol, a type of alcohol, has been widely used from the chemical industry to the food industry. In this study, toxic effects of n-butanol's different concentrations (10, 50, 250, 500, 750, 1,000, and 1,250 mg/L) in Zebrafish Danio rerio embryos and larvae were investigated. For this purpose, Zebrafish embryos were exposed to n-butanol in acute semistatic applications. Teratogenic effects such as cardiac edema, scoliosis, lordosis, head development abnormality, yolk sac edema, and tail abnormality were determined at different time intervals (24, 48, 72, 96, and 120 h). Additionally, histopathological abnormalities such as vacuole formation in brain tissue and necrosis in liver tissue were observed at high doses (500, 750, and 1,000 mg/L) in all treatment groups at 96 h. It was determined that heart rate decreased at 48, 72, and 96 h due to an increase in concentration. In addition, alcohol-induced eye size reduction (microphthalmia) and single eye formation (cyclopia) are also among the effects observed in our research findings. In conclusion, n-butanol has been observed to cause intense neurotoxic, teratogenic, and cardiotoxic effects in Zebrafish embryos and larvae.

Canine distemper virus induces downregulation of GABAA,GABAB, and GAT1 expression in brain tissue of dogs.

The aim of the study was to determine the expression profiles of GABAA, GABAB, and GAT1 using RT-PCR and the immunoreactivity of GAT1 via immunohistochemical and immunofluorescence assays in CDV-infected brain tissue of dogs. For this purpose, dogs with CDV and dogs without CDV were selected. The mRNA transcript levels of GABAA, GABAB, and GAT1 were significantly downregulated in brain tissue in the CDV-infected group as compared with that in non-CDV-infected brain tissue in the control group (p < 0.01, p < 0.001). In addition, the immunoreactivity of GAT1 in CDV-infected brain tissue was significantly lower than in the uninfected group (p < 0.05). We conclude that one of the main causes of myoclonus in CDV infections may be the blockage of postsynaptic inhibition in neurons or a lack of metabolism of GABA. In addition, a GABA neurotransmission imbalance could play a role in demyelination in CDV infections.

Neuroprotective effect of rutin against colistin-induced oxidative stress, inflammation and apoptosis in rat brain associated with the CREB/BDNF expressions.

The purpose of the current study was to examine the neuroprotective effect of rutin against colistin-induced neurotoxicity in rats. Thirty-five male Sprague Dawley rats were randomly divided into 5 groups. The control group (orally received physiological saline), the rutin group (orally administered 100 mg/kg body weight), the colistin group (i.p. administered 15 mg/kg body weight), the Col + Rut 50 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 50 mg/kg body weight of rutin), the Col + Rut 100 group (i.p. administered 15 mg/kg body weight of colistin, and orally received 100 mg/kg body weight of rutin). Administration of colistin increased levels of glial fibrillary acidic protein and brain-derived neurotrophic factor and acetylcholinesterase and butyrylcholinesterase activities while decreasing level of cyclic AMP response element binding protein and extracellular signal regulated kinases 1 and 2 (ERK1/2) expressions. Colistin increased oxidative impairments as evidenced by a decrease in level of nuclear factor erythroid 2-related factor 2 (Nrf-2), glutathione, superoxide dismutase, glutathione peroxidase and catalase activities, and increased malondialdehyde content. Colistin also increased the levels of the apoptotic and inflammatoric parameters such as cysteine aspartate specific protease-3 (caspase-3), p53, B-cell lymphoma-2 (Bcl-2), nuclear factor kappa B (NF-κB), Bcl-2 associated X protein (Bax), tumor necrosis factor-α (TNF-α) and neuronal nitric oxide synthase (nNOS). Rutin treatment restored the brain function by attenuating colistin-induced oxidative stress, apoptosis, inflammation, histopathological and immunohistochemical alteration suggesting that rutin supplementation mitigated colistin-induced neurotoxicity in male rats.

Effect of chrysin on methotrexate-induced testicular damage in rats.

This study was conducted on 28 male Wistar albino rats to determine the effects of chrysin on methotrexate-induced damage to testicular tissue. Rats were grouped into four groups of seven rats reach: Group 1 (n = 7) was the control group to which no drugs were administered; this group was only provided with food and water. Group 2 (n = 7) was administered 20 mg/kg of methotrexate once intraperitoneally. Group 3 (n = 7) was administered 50 mg/kg of chrysin for 7 days orally. Group 4 (n = 7) was administered 20 mg/kg of methotrexate once intraperitoneally, followed by oral administration of 50 mg/kg of chrysin for 7 days. At the end of the experiment, rats were anaesthetised, rat testes were removed, and spermatozoon was obtained from the cauda epididymis. It was determined that sperm count and motility, glutathione peroxidase, superoxide dismutase and catalase activities decreased in the methotrexate group, whereas malondialdehyde, tumour necrosis factor-α, interleukin-1ß and nuclear kappa factor B expression levels increased. Furthermore, damage to tubulus seminiferus structures and affusion in germ cells was identified. In the methotrexate + chrysin administered group, sperm count improved, biochemical enzyme levels increased, and structural improvements were observed in testicular tubules. These findings demonstrated that chrysin plays a protective role in testicular damage in rats.

Neuroprotective effects of dietary borax in the brain tissue of rainbow trout (Oncorhynchus mykiss) exposed to copper-induced toxicity.

We aimed to investigate the modulating effects of dietary borax on the pathways in rainbow trout brain exposed to copper. For this aim, a comprehensive assessment was performed including biochemical (acetylcholinesterase (AChE), malondialdehyde (MDA), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), and caspase-3 levels) and transcriptional parameters (heat shock protein 70 (HSP70) and cytochromes P450 (CYP1A), glutathione peroxidase (gpx), superoxide dismutase (sod), and catalase (cat)) parameters and immunohistochemically staining of 8-OHdG. Special fish feed diets were prepared for the trial. These diets contained different concentrations of borax (1.25, 2.5, and 5 mg/kg) and/or copper (500 and 1000 mg/kg) at the period of pre- and co-treatment strategies for 21 days. At the end of the treatment periods, brain tissue was sampled for each experimental group. As a result, the biochemical parameters were increased and AChE activity decreased in the copper and copper-combined groups in comparison with the control group and also with only borax applications (p < 0.05). We observed an increase or decrease in particular biochemical parameters for the borax group in every application and we established that borax had protective effect against copper toxicity by decreasing and/or increasing the relevant biochemical parameters in brain tissue of fish. The biochemical results of borax and its combinations corresponded to the observations of gene expression data, which similarly concluded that HSP70 and CYP1A genes were strongly induced by copper (p < 0.05). In addition, the expression levels of the sod, cat, and gpx genes in the fish brains exposed to borax and the borax combination groups were significantly higher than the only copper-treated groups. In conclusion, borax supplementation provided significant protection against copper-induced neurotoxicity in trout.

Ameliorative Effect of Carvacrol on Cisplatin-Induced Reproductive Damage in Male Rats.

Cisplatin (CP) treatment causes the damage in male reproductive system. Carvacrol (CARV) is an antioxidant that is naturally found in some plants. We aimed to investigate the effect of CARV on CP-induced reproductive toxicity in male rats. Eighteen adult male Sprague-Dawley rats were used. The control group (n = 6) was treated orally with physiological saline (PS) daily for 14 days and a single intraperitoneal (IP) PS injection on day 10. The CP group (n = 6) was administered with daily oral PS for 14 days and a single IP injection of 10 mg/kg CP on day 10. The CARV + CP group (n = 6) was treated with daily 75 mg/kg oral CARV for 14 days and a single IP injection of 10 mg/kg CP on day 10. CP treatment caused the damage on some spermatological parameters (motility, live sperm rate, and abnormal sperm rate), increased the oxidative stress, and induced testicular degeneration and apoptosis. However, CARV treatment mitigates CP-induced reproductive toxicity.

The possible role of interleukin-33 as a new player in the pathogenesis of contrast-induced nephropathy in diabetic rats.

INTRODUCTION: Patients with diabetic kidney disease (DKD) are more prone to contrast-induced nephropathy (CN). Apoptosis and autophagy were found to be essential in the pathogenesis of DKD. Interleukin-33 (IL-33) is a cytokine, but its role in DKD and CN is unknown. As IL-33 is modulated by apoptosis, we aimed to determine the relationship between IL-33 apoptosis and autophagy in DKD with CN. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were enrolled and randomly allocated into three groups. The first group was comprised of healthy rats (HRs), whereas the other two groups were made up of diabetic rats (DRs) and diabetic rats with CN (DRs + CN). All groups except the HRs received 50 mg/kg/day of streptozotocin (STZ). The DRs + CN group was induced by administering 1.5 mg/kg of intravenous radiocontrast dye on the 35th day. RESULTS: We observed increased IL-33 in the kidney tissue following induction of CN in the DRs. The DRs showed moderate immunopositivity, and the DRs + CN showed severe immunopositivity for caspase-3, cleaved caspase-3, caspase-8, caspase-9, LC3B, and Beclin-1 in tubular cells and glomeruli. The DRs also showed moderate immunopositivity in tubular cells, and the DRs + CN group showed severe immunopositivity for IL-33 in tubular cells. Increased caspase-3 was found in both glomeruli and tubuli; however, we could not demonstrate IL-33 in glomeruli. This could be secondary to inactivation of IL-33 via increased caspase-3 activity. CONCLUSION: The release of IL-33 from necrotic cells might induce autophagy, which can further balance the effects of increased apoptosis secondary to CN in DKD.

Quinacrine, a PLA2 inhibitor, alleviates LPS-induced acute kidney injury in rats: Involvement of TLR4/NF-κB/TNF α-mediated signaling.

Acute Kidney Injury (AKI) is a major factor in sepsis-related mortality and may occur due to lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria that triggers a systemic acute inflammatory response. Quinacrine's (QC) renoprotective properties in sepsis and the underlying mechanism, however, are still not fully understood. This study was done to investigate the anti-inflammatory, antioxidative, and anti-apoptotic effects of QC, a phospholipase A2 (PLA2) inhibitor, against LPS-induced AKI. Rats were randomly divided into five groups: control group, QC30 group, LPS group, LPS+QC 10 group, and LPS+QC 30 group. The rats were administered intraperitoneally QC (10 and 30 mg/kg) for 3 days (once a day) prior to injection of LPS (3 mg/kg). Six hours after the LPS injection, the histopathological changes, oxidative stress, inflammation, and apoptosis in the collected kidney tissues were detected by hematoxylin and eosin staining, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and immunohistochemistry staining, respectively. QC pretreatment could successfully attenuate LPS-induced AKI, as evidenced by a decrease in tissue histopathological injury. Meanwhile, QC alleviated LPS-induced kidney oxidative stress; it reduced MDA levels and increased levels of SOD, CAT, GPX, and GSH. LPS-induced elevations in kidney TLR4, NF-κB, TNF-α, IL-1ß, IL-6, PLA2, caspase 3, and Bax contents were significantly attenuated in QC-treated groups. Our findings revealed a significant effect of QC: protecting against LPS-induced AKI through inhibition of PLA2 and decreasing inflammation, oxidative stress, and apoptosis. To treat LPS-induced AKI, QC may be an effective substance with an excellent protection profile.

Alleviating sepsis: Revealing the protective role of costunolide in a cecal ligation and puncture rat model.

Objectives: Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP). Materials and Methods: We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1ß), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings. Results: Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups. Conclusion: Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.

Chrysin attenuates paclitaxel-induced hepatorenal toxicity in rats by suppressing oxidative damage, inflammation, and apoptosis.

AIMS: Paclitaxel (Pax) is a chemotherapeutic drug from the taxane family that is used in the treatment of human cancer, including ovarian, breast, and non-small cell lung carcinoma. Chrysin (CR) has antioxidant, anti-inflammatory, anti-apoptotic, anti-diabetic, and anti-carcinogenic properties, as well as hepatoprotective and renoprotective activities. In the present study, we evaluated the protective effect of CR against Pax-induced hepatorenal toxicity on inflammation, apoptosis, antioxidant levels, oxidative DNA damage, and histopathology in rats. MATERIAL AND METHODS: Thirty-five male Sprague-Dawley rats were divided into five groups (n = 7): Group I (normal control), Group II (CR alone at a dose of 50 mg/kg), Group III (Pax at a dose of 2 mg/kg), Group IV (Pax+CR 25), and Group V (Pax+CR 50). The expressions of apoptotic (Bax and Bcl-2) and antioxidant genes (SOD1, CAT, GPx3, and GST) were evaluated using RT-PCR from paraffin sections. Caspase 3, KIM-1, NF-kB, COX-2, and 8-OHdG were also determined by immunohistochemical examination. KEY FINDINGS: The results revealed that Pax exposure caused hepatic and renal damage in rats, which was indicated by a significant elevation of caspase 3, Bax, KIM-1, NF-kB, COX-2, and 8-OHdG. However, there was a marked downregulation in the expressions of the Bcl-2, SOD1, CAT, GPx3, and GST genes. In contrast, rats given CR in combination showed better gene expression, histological structure, and immunohistochemical staining results. SIGNIFICANCE: Consequently, CR exhibited the ability to reduce oxidative DNA damage, exert anti-apoptotic and anti-inflammatory properties, and mitigate the toxic effects of Pax-induced hepatorenal toxicity.

Costunolide prevents renal ischemia-reperfusion injury in rats by reducing autophagy, apoptosis, inflammation, and DNA damage.

Objectives: Renal ischemia-reperfusion (I/R) is a vital health condition leading to acute kidney injury. Costunolide (COST) is an actively used molecule clinically for its anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, we searched for the possible protective effects of COST against renal ischemia/reperfusion (I/R) injury in rats. Materials and Methods: We established a renal I/R rat model. We divided forty rats into four groups: group I (sham), group II (I/R), group III (I/R+COST 5 mg/kg), and group IV (I/R+COST 10 mg/kg). We collected blood, kidney, and lung samples for analysis. Results: COST administration performed anti-oxidant and anti-inflammatory activity by reducing oxidant parameters and proinflammatory cytokine levels. COST alleviated DNA damage through declining 8-hydroxydeoxyguanosine (8-OHdG) levels. In addition, COST diminished tubular damage and inflammation by reducing kidney injury molecule-1 (KIM-1) production. COST administration also ameliorated apoptosis and autophagy by decreasing caspase-3 and microtubule-associated protein light chain 3B (MAPLC3, LC3B) expression. Conclusion: COST demonstrated protective effects against renal I/R-induced injury.