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DINP aggravates autoimmune thyroid disease through activation of the Akt/mTOR pathway and suppression of autophagy in Wistar rats
2019
Duan, Jiufei | Deng, Ting | Kang, Jun | Chen, Mingqing
Di-isononyl phthalate (DINP) is used as a substitute for traditional phthalates, in a wide range of applications. However, there is growing concern regarding its toxicity. Studies have indicated that DINP is related to thyroid hormone disorder and that phthalates can affect thyroid normal function. In this study, we aim to determine any effects of DINP exposure on autoimmune thyroid disease (AITD), the most common autoimmune disease, and to understand the underlying causal mechanism. AITD model Wistar rats were exposed to 0.15 mg/kg, 1.5 mg/kg or 15 mg/kg DINP. We assessed the thyroid globulin antibody levels, Th1/Th2 balance, histopathological changes and caspase-3 levels in the thyroid. The data show that exposure to DINP does indeed aggravate AITD. To explore the underlying mechanisms, we examined the levels of microtubule-associated protein 1 light chain 3 B (LC3B), Sequestosome 1 (SQSTM1) and the appearance of autophagosomes or autolysosomes to assess autophagy in the thyroid. The results show that DINP can suppress normal autophagy. We found that DINP induced an exacerbation of oxidative stress and the activation of the Akt/mTOR pathway, indicating that oxidative stress and activation of mTOR may play a key role in these processes. Moreover, the activation of mTOR also promoted the expression of IL-17. Importantly, blocking oxidative stress with VE or blocking Akt/mTOR with rapamycin mitigated the exacerbation of AITD and the suppression of normal autophagy. All these results indicate that exposure to DINP, especially high doses of DINP, can aggravate oxidative stress and activate the Akt/mTOR pathway. This exposure then leads to a suppression of normal autophagy and expression of IL-17 in the thyroid, resulting in an eventual exacerbation of AITD.
Show more [+] Less [-]Disruption of thyroid hormone regulated proteins and gene expression by polychlorinated biphenyls, polybrominated diphenyl ethers and new flame retardants in residents of an e-waste region
2019
Guo, Ling-Chuan | Yu, Shengbing | Wu, De | Huang, Jinxu | Liu, Tao | Xiao, Jianpeng | Huang, Weixiong | Gao, Yanhong | Li, Xing | Zeng, Weilin | Rutherford, Shannon | Ma, Wenjun | Zhang, Yonghui | Lin, Lifeng
Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and new flame retardants (NFRs) are known thyroid hormone (TH) disruptors, but their disrupting mechanisms in humans are not completely understood. In this study, we aimed to explore the disrupting mechanisms of the aforementioned chemicals via examining TH-regulated proteins and gene expression in human serum. Adult participants from an e-waste dismantling (exposed group) and a control region (control group) in South China provided blood samples for the research. Some compounds of PCBs, PBDEs, and NFRs showed strong binding affinity to the thyroid-stimulating hormone (TSH), thyroglobulin, thyroxine-binding globulin (TBG), gene expression of TH receptor α (TRα) and β, and iodothyronine deiodinase I (ID1). The highly exposed individuals had lower levels of TBG, TSH, and expression of TRα, but higher expression of ID1 than those of the control group. The disruption of TH-regulated proteins and gene expression suggested the exertion of different and, at times, even contradictory effects on TH disruption. However, no statistically significant difference was found in the TH levels between the exposed and the control group, implying that the TH disruption induced by these chemicals depends on the combined influence of multiple mechanisms. Gene expression appears to be an effective approach for investigations of TH disruption and the potential health effects.
Show more [+] Less [-]Reducing ammonia emission by aluminum sulfate addition in litter and its influence on productive, reproductive, and physiological parameters of dual-purpose breeding hens [Erratum: April 2022, v.29(17); p.25111]
2022
Attia, Youssef A. | Bovera, Fulvia | Hassan, Reda A. | Hassan, Ebtehal A. | Attia, Khalil M. | Assar, Mohamed H. | Tawfeek, Fouad
This research investigated the impact of aluminum sulfate (AS) as amendment to different types of litter (new, reused, and mixed litters) for reducing ammonia emission and improving productive performance of local dual-purpose breeding hens. A total of 450 hens and 60 cocks from the Inshas strain were randomly assigned to six groups (five replicates each of 15 hens + 2 cocks) raised in pen floor furnished with a wheat straw litter. The groups included: (1) new, (2) reused, (3) mixed (50% new + 50% reused) litter; the other groups (4, 5 and 6) were respectively housed on the same litter as groups 1, 2 and 3 but with the addition of 495 g of AS/m² litter. The feed conversion ratio was better for layers raised on new litter with or without AS than other groups. Different kinds of litter had different moisture (p < 0.05) and pH (p < 0.05) values. Birds raised on litter types treated with AS significantly (p < 0.05) decreased intestinal pH and decreased total bacterial count compared to the same litter types without AS at the end of the experiment. Birds raised on new litter supplemented with AS had the highest plasma T3, total protein, globulin, Hgb, and PCV% and the lowest levels of uric acid and cholesterol at the end of the experimental period. Therefore, litter amendment with AS, also the mixed or reused one, could be recommended to reduce ammonia and, in turn, increasing plasma T3 and decreasing total bacterial count, leading to increasing bird’s performance.
Show more [+] Less [-]Nanoplastics-induced oxidative stress, antioxidant defense, and physiological response in exposed Wistar albino rats
2022
Babaei, Ali Akbar | Rafiee, Mohammad | Khodagholi, Fariba | Ahmadpour, Elham | Amereh, Fatemeh
Nowadays, plastic pollution and in particular nano(micro)plastics is considered as an issue of global concern in environmental samples. The present work was conducted to clarify the oxidative stress of polystyrene nanoplastics (PS-NPs) exposure and physiological response of male Wistar rats. Animals were treated orally with PS-NPs at four doses (1, 3, 6, and10 mg/kg-day) for 5 weeks. Results demonstrated the accumulation of PS-NPs through whole body scanning and also a dose-dependent increase in the production of reactive oxygen species (ROS). Alterations in antioxidant responses including serum levels of catalase (CAT) and total glutathione content were noticed, but not superoxide dismutase (SOD), pointing towards the perturbation of redox state induced by exposure conditions. Biochemical parameters viz. glucose, cortisol, lipase, lactate, lactate dehydrogenase (LDH), alkaline phosphatase, gamma-glutamyl transpeptidase (GGT), triglycerides, and urea showed a significant increase, while total protein, albumin, and globulin levels showed an appreciable decline. The pattern of associations noticed with AChE activity and biochemical responses in our study suggests the possibility that a neurobehavioral effect or dysfunctions in energy metabolism may be the potential modes of action, possibly through stress response as well as liver function. Perturbations of creatinine and uric acid levels are indeed plausible biological explanations for the association with kidney dysfunction. Although we provided a new scientific clue for exploring the biological consequences of NPs which might induce effects such as oxidative stress relating to the induction of antioxidant enzymes, the results warrant additional research with a larger sample size.
Show more [+] Less [-]Amelioration of aluminum-induced hepatic and nephrotoxicity by Premna odorata extract is mediated by lowering MMP9 and TGF-β gene alterations in Wistar rat
2022
Ahmed, Walaa M. S. | Ibrahim, Marwa A. | Helmy, Nermeen A. | ElKashlan, Akram M. | Elmaidomy, Abeer H. | Zaki, Amr R.
This study aims to investigate the effect of Premna odorata (P. odorata) (Lamiaceae) on the hepatic and nephrotoxicity induced by aluminum chloride (AlCl₃) in rat. Wistar male rats were equally classified into four groups: control, P. odorata extract (500 mg/kg B.W.), AlCl₃ (70 mg/kg B.W.), and P. odorata extract plus AlCl₃ groups. All treatments were given orally for 4 weeks. Serum transaminases and some biochemical parameters, hepatic and renal antioxidant/oxidant biomarker; tumor necrosis factor-α (TNF-α); matrix metalloproteinase (MMP9) and transforming growth factor-β (TGF-β) mRNA expression; histopathological examination of the liver, and kidneys were investigated. The obtained results revealed that AlCl₃ significantly increased the activities of serum aspartate transaminase, alanine transaminase, and alkaline phosphatase as well as produced a significant increase in total cholesterol, triglyceride, urea, and creatinine concentrations, while there were no changes observed in the total protein, albumin, and globulin concentrations. Also, aluminum administration significantly decreased the reduced glutathione content and increased the catalase activity, malondialdehyde, and TNF-α concentrations in the liver and kidney tissue. Moreover, AlCl₃ results in congestion, degeneration, and inflammation of the liver and kidney tissue. Co-treatment of P. odorata extract with AlCl₃ alleviated its harmful effects on the previous parameters and reduced the histopathological alterations induced by AlCl₃. Therefore, Premna odorata may have a potent protective effect against oxidative stress induced by Al toxicity through downregulation of MMP9 and TGF-β gene expression.
Show more [+] Less [-]Assessment of the potential threat of nickel(II) oxide nanoparticles to fish Heteropneustes fossilis associated with the changes in haematological, biochemical and enzymological parameters
2021
The present study has been conducted to evaluate the potential threat of NiO nanoparticles (NiO NPs) on an edible fish Heteropneustes fossilis. Fishes selected for the study were exposed to four concentrations of NiO NPs (12, 24, 36 and 48 mg/l) for the period of 14 days, and various haematological, biochemical and enzymological changes in the exposed fishes were examined. Results revealed that maximum fluctuations were seen in 48-mg/l-exposed fishes when compared with the control in terms of the haematological parameters (RBC count, WBC count, Hb content, Ht% and O₂ carrying capacity of blood), enzymatic activities (AST, ALP, ALT and LDH) and biochemical parameters (level of cholesterol, triglycerides, glucose, total protein, albumin, globulin, bilirubin and creatinine). However, 12 mg/l treatment to the fishes showed its least impact on aforesaid parameters. Furthermore, Ni accumulation and changes in cortisol level in the blood were also noticed in all the treated fishes. Structural changes, such as membrane and nuclear disintegration, micronucleus, deformed and vacuolated cells, and enucleation were also observed in RBCs of NiO NP–treated fishes. Conclusively, our study provides useful information and insight for the possible ecotoxicity of NiO NPs on aquatic organisms and emphasizes upon the importance of treatment of effluents containing nanoparticles before their release into the aquatic system.
Show more [+] Less [-]Does the adsorbent capacity of orange and banana peels toward silver nanoparticles improve the biochemical status of Oreochromis niloticus?
2021
Abdel-Khalek, Amr Adel | Hamed, Aliaa | Hasheesh, Wafaa S.F.
Silver nanoparticles (Ag NPs) have wide medical and industrial applications; therefore, their release into aquatic environments is a problematic issue. The present study aims to evaluate the removal efficiency of Ag NPs from water using orange peel (OP) and banana peel (BP) to moderate their toxicity on Oreochromis niloticus. Fish were divided into 4 groups: control group (dechlorinated tap water), Ag NPs (4 mg/L) exposed group, Ag NPs (4 mg/L) + OP (40 mg/L) group, and Ag NPs (4 mg/L) + BP (40 mg/L) group for 24 h, 48 h, and 96 h. The adsorptive ability of both peels was confirmed by scanning electron microscope and energy-dispersive X-ray spectroscopy after the exposure processes. The biochemical results revealed a gradual elevation in plasma glucose, total proteins, globulin, liver enzymes (AST, ALT, and ALP), creatinine, and uric acid after Ag NPs exposure, while albumin and total lipid concentrations were significantly decreased. The recorded antioxidant biomarkers in gills, and liver tissues after Ag NPs exposure showed severe oxidative damages (maximally after 96 h) as indicated by marked elevations in thiobarbituric acid reactive substances, glutathione peroxidase, catalase, and superoxide dismutase values, and decreased glutathione reduced content. All studied parameters restored more or less to that of control groups after OP and BP water treatment. The adsorbent abilities of both peels could reduce Ag NPs bioavailability and moderate their toxicological impacts.
Show more [+] Less [-]Effect of feeding dried sweet orange (Citrus sinensis) peel and lemon grass (Cymbopogon citratus) leaves on growth performance, carcass traits, serum metabolites and antioxidant status in broiler during the finisher phase
2016
Alzawqari, M. H. | Al-Baddany, A. A. | Al-Baadani, H. H. | Alhidary, I. A. | Khan, Rifat Ullah | Aqil, G. M. | Abdurab, A.
The current experiment was conducted to evaluate the effects of feeding dried sweet orange peel (SOP) and lemon grass leaves (LGL) as feed additives on broiler growth performance, serum metabolites, and antioxidant status. A total of 192-day-old (Ross 308) broiler chickens were distributed randomly into 4 dietary treatments with 4 replicates per each treatment. The dietary treatments included a control diet without any feed additive (T1), a diet containing 0.8 % SOP (T2), a diet containing 0.8 % LGL (T3), and a diet containing combination of 0.4 % SOP + 0.4 % LGL (T4) was fed during the growth period from 22 to 42 days. Feed intake (FI), body weight gain (BWG), feed conversion ratio (FCR), carcass traits, serum components, and antioxidant status were measured. At the end of the experimental period, the results indicated that supplementation of SOP and LGL alone or in combination did not significantly (P > 0.05) affect BWG, FI, FCR, and carcass characteristics in broiler chickens. Serum total protein was increased significantly (P < 0.05) in T3 and T4 compared to the other treatments. Also, serum globulin increased significantly (P < 0.05) in the treated groups. Serum glucose, low density lipoprotein, triglyceride, and very low density lipoprotein decreased significantly (P < 0.05) in the treatment groups, while cholesterol and high-density lipoprotein decreased in T2 compared to the other groups. Significantly (P < 0.05) higher total antioxidant status was observed in T2 compared to the other treatments. In conclusion, these results indicate that SOP, LGL, and their combination may positively modify some serum components and the antioxidant status without any beneficial effect on growth performance and carcass traits in broiler chickens.
Show more [+] Less [-]Respiratory, hepatic, renal, and hematological disorders among adolescent females environmentally exposed to pesticides, Menoufia governorate, Egypt
2022
Abdel-Rasoul, Gaafar Mohamed | Salem, Eman Abdel-Azeem | Hendy, Olfat Mohamed | Rohlman, Diane | Abdel Latif, Asmaa Abdel Raheem | Elbadry, Aziza Saad
Adolescent females are often environmentally exposed to pesticides by living near agricultural fields, by using pesticides at home, or by having contact with contaminated clothes and pesticide application work tools. This study assessed respiratory, hepatic, renal, and hematological health disorders that might arise due to environmental exposure to pesticides among adolescent females. A cross-sectional study was conducted with 100 adolescent females environmentally exposed to pesticides that had one or more of their family members working as seasonal pesticide applicators and 50 nonexposed (control) adolescent females from Menoufia governorate, Egypt. The studied period of pesticide application season of the cotton crop was from May 1 to September 1, 2017. Participants completed a self-administered questionnaire about pesticide exposure and respiratory, hepatic, renal, and hematological disorders. In addition, serum acetylcholinesterase (AChE), spirometry, complete blood count, and liver and kidney function tests were measured pre and post-pesticide application season. The control adolescent females had a higher AChE activity, a lower prevalence of respiratory symptoms, and higher means of spirometric measurements than the exposed group. During the pre- and postseason, the exposed group presented a prevalence of (6%, 24%) for cough, (4%, 11%) for rhinitis, and (6%, 26%) for dyspnea during the pre and postseason, respectively. In addition, there was a decrease in means of spirometric measurements (FEV₁%, FEV₁/FVC%, FEF ₂₅–₇₅%, and PEF%) in the postseason compared to preseason among the exposed group. Also, there were significant associations between (AChE) activity and both the prevalence of respiratory manifestations and spirometric measurements among the exposed females. On the other hand, there was a statistically significant increase in red blood corpuscle (RBC) and lymphocyte counts, and a statistically significantly lower mean hemoglobin level among the exposed group (postseason) than each of their pre-season values and the control group (P < 0.05). AChE level, total protein, albumin, and albumin/globulin (A/G) ratio levels were statistically significantly lower, while SGPT, SGOT and globulin, blood urea, and serum creatinine mean levels were statistically significantly higher among the exposed group (postseason) than either of their preseason or the control group (P < 0.05). There was a positive correlation between the AChE level and all studied CBC parameters for the exposed group reaching a statistically significant level with basophils (P < 0.05). Also, there was a negative correlation between the AChE level and each of SGPT, SGOT, ALP, globulin, blood urea, and serum creatinine for the exposed group reaching a statistically significant level with each of SGPT and SGOT (P < 0.05). At the same time, a nonsignificant positive correlation was found between AChE level and each of total protein, albumin, and A/G ratio (P > 0.05). So, environmental exposure to organophosphorus pesticides has a detrimental impact on respiratory, hepatic, renal, and hematological systems of adolescent females living in rural districts at the Menoufia governorate. Educational and training intervention programs on pesticide handling and safety precautions are recommended for protecting both pesticide workers and their family members who might be exposed.
Show more [+] Less [-]Comparative assessment on the probable mechanisms underlying the hepatorenal toxicity of commercial imidacloprid and hexaflumuron formulations in rats
2022
Hassanen, Eman I. | Hussien, Ahmed M. | Mehanna, Sally | Ibrahim, Marwa A. | Hassan, Neven H.
Pesticides are viewed as a major wellspring of ecological contamination and causing serious risky consequences for people and animals. Imidacloprid (IM) and hexaflumuron (HFM) are extensively utilized insect poisons for crop assurance on the planet. A few investigations examined IM harmfulness in rodents, but its exact mechanism hasn’t been mentioned previously as well as the toxicity of HFM doesn’t elucidate yet. For this reason, the present study was designed to explore the mechanism of each IM and HFM–evoked rat liver and kidney toxicity and to understand its molecular mechanism. 21 male Wistar albino rats were divided into 3 groups, as follows: group (1), normal saline; group (2), IM; and group (3), HFM. Both insecticides were orally administered every day for 28 days at a dose equal to 1/10 LD50 from the active ingredient. After 28 days postdosing, rats were anesthetized to collect blood samples then euthanized to collect liver and kidney tissue specimens. The results showed marked changes in walking, body tension, alertness, and head movement with a significant reduction in rats’ body weight in both IM and HFM receiving groups. Significant increases in MDA levels and decrease of GHS levels were recorded in liver and kidney homogenates of either IM or HFM groups. Liver and kidney tissues obtained from both pesticide receiving groups showed extensive histopathological alterations with a significant increase in the serum levels of ALT, AST, urea, and creatinine and a decrease in total proteins, albumin, and globulin levels. In addition, there was upregulation of the transcript levels of casp-3, JNK, and HO-1 genes with strong immunopositivity of casp-3, TNF-ὰ, and NF-KB protein expressions in the liver and kidneys of rats receiving either IM or HFM compared with the control group. In all studied parameters, HFM caused hepatorenal toxicity more than those induced by IM. We can conclude that each IM and HFM provoked liver and kidneys damage through overproduction of ROS, activation of NF-KB signaling pathways and mitochondrial/JNK-dependent apoptosis pathway.
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